1 1 NO. 90-CI-06033 JEFFERSON CIRCUIT COURT DIVISION ONE 2 3 4 JOYCE FENTRESS, et al PLAINTIFFS 5 6 VS TRANSCRIPT_OF_THE_PROCEEDINGS __________ __ ___ ___________ 7 8 9 SHEA COMMUNICATIONS, et al DEFENDANTS 10 11 * * * 12 13 14 TUESDAY, OCTOBER 18, 1994 15 VOLUME XVII 16 17 * * * 18 19 20 21 _____________________________________________________________ REPORTER: JULIA K. McBRIDE 22 Coulter, Shay, McBride & Rice 1221 Starks Building 23 455 South Fourth Avenue Louisville, Kentucky 40202 24 (502) 582-1627 FAX: (502) 587-6299 25 2 1 2 I_N_D_E_X _ _ _ _ _ 3 4 WITNESS: DOCTOR_PETER_BREGGIN - Continued _______ ______ _____ _______ 5 Examination by Mr. Smith.................................6 6 7 * * * 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 3 1 2 A_P_P_E_A_R_A_N_C_E_S _ _ _ _ _ _ _ _ _ _ _ 3 4 FOR THE PLAINTIFFS: 5 PAUL L. SMITH Suite 745 6 Campbell Center II 8150 North Central Expressway 7 Dallas, Texas 75206 8 NANCY ZETTLER 1405 West Norwell Lane 9 Schaumburg, Illinois 60193 10 IRVIN D. FOLEY Rubin, Hays & Foley 11 300 South, First Trust Centre Louisville, Kentucky 40202 12 13 FOR THE DEFENDANT: 14 EDWARD H. STOPHER Boehl, Stopher & Graves 15 2300 Providian Center Louisville, Kentucky 40202 16 JOE C. FREEMAN, JR. 17 LAWRENCE J. MYERS Freeman & Hawkins 18 4000 One Peachtree Center 303 Peachtree Street, N.E. 19 Atlanta, Georgia 30308 20 * * * 21 22 23 24 25 4 1 The Transcript of the Proceedings, taken before 2 The Honorable John Potter in the Multipurpose Courtroom, Old 3 Jail Office Building, Louisville, Kentucky, commencing on 4 Tuesday, October 18, 1994, at approximately 9:05 A.M., said 5 proceedings occurred as follows: 6 7 * * * 8 9 SHERIFF CECIL: The jury is now entering. All 10 rise. The Honorable Judge John Potter is now presiding. 11 Court is now in session. You may be seated. 12 JUDGE POTTER: Please be seated. Ladies and 13 gentlemen of the jury, I take it did anybody have any 14 difficulty with staying away from the newspapers and your 15 family and whatnot last night? How about you, Ms. Whitehouse? 16 We're going out of order. 17 JUROR WHITEHOUSE: No problem. 18 JUDGE POTTER: Okay. Let me mention one other 19 thing to you. The documents that you-all are getting, as I 20 told you either yesterday or last week, you will be allowed to 21 keep. The initial thought was that at some point we'd collect 22 them back up from you just because of the bulk, but I realize 23 as you were going along it's helpful for you to mark on them 24 or use them. So as I told you, they will not be taken away 25 from you when you go to the jury room. Because it's getting 5 1 kind of bulky, what we're going to do later today is my 2 clerk -- my secretary is preparing up some boxes, you know, 3 about -- not one of those huge banker's boxes but one -- I 4 hate to say it -- about the size of a case of whiskey. Maybe 5 some of you-all have seen that. And it will be just plain 6 boxes. It will have your name on it and that way you can 7 store older stuff in there if you want to. And your box is 8 your box, just like in kindergarten. Nobody is supposed to 9 mess with your box. 10 Okay. I've also told the attorneys this and so 11 I told them that if they want to, at the beginning of a day, 12 if they look ahead and they say, you know, "Gee, I think it 13 would be good if the jury had a certain exhibit number," 14 they'll tell my sheriff and, of course, you don't have to 15 bring it out. You can keep bringing everything you want. You 16 can bring nothing or bring it all or whatever, but on certain 17 days my sheriff might alert you that a previous exhibit, one 18 of the attorneys thinks it would be helpful if you had it. 19 Okay? Okay. 20 Doctor Breggin, I remind you you're still under 21 oath. 22 Mr. Smith. 23 24 25 6 1 EXAMINATION ___________ 2 3 BY_MR._SMITH:(Cont'd) __ ___ ______ 4 Q. Doctor Breggin, we were in a little rush last 5 night and I may have gone through your past history a little 6 too quick. Let's back up a little bit and let me ask you 7 about some other things that you've done since you've become a 8 medical doctor. All right, sir? 9 JUDGE POTTER: Doctor Breggin, the microphone 10 that comes out in the courtroom is not the one that's there. 11 But you see the little brown one; that's the one that you need 12 to have out in front of you and, also, don't put papers and 13 things over it because it makes noise. 14 Go ahead, Mr. Smith. I didn't mean to 15 interrupt. 16 Q. Once you began your psychiatric practice and 17 started speaking at various seminars and meeting with various 18 professionals on issues of psychiatry and drug treatment in 19 psychiatry, did there come an occasion when you started an 20 entity known as the Center for the Study of Psychiatry? 21 A. Yes, sir. I founded that in the early '70s, the 22 center. 23 Q. Tell the jury about the reason for that and what 24 it is. 25 A. Well, the center is a network of professional 7 1 people. We have about 25 psychiatrists, 30 or 40 2 psychologists, some members of the United States Congress are 3 on the board of directors and actively involved over the 4 years, and it's a network of people who have similar concerns, 5 similar interests to my own philosophy that have kind of 6 collected as a network over the years. We have a newsletter 7 that comes out 4 times a year, and we make occasional reports 8 on issues of concern to us. I've made some reports through 9 the center on Prozac, for example. 10 Q. And is that an organization that is examining 11 topical issues in psychiatry as they come up? 12 A. Yes, very much so. It's a nonprofit 13 organization. It's a tax-exempt organization. It's for 14 educational purposes. 15 Q. Have you served as an adviser on any committees 16 or things of that nature? 17 A. Well, currently I'm a consultant to the research 18 committee of the American Academy of Psychotherapists. I 19 don't think I mentioned the academy. That's a national 20 organization that you have to be elected to for having certain 21 credentials as a psychotherapist and it has psychiatrists 22 psychologists, social workers, anyone who does talking therapy 23 can be elected to the American Academy of Psychotherapists. 24 Q. And what is your status? 25 A. Well, I'm a member, but I'm also a consultant to 8 1 the research committee. 2 Q. Research into new techniques or existing 3 techniques in psychotherapy? 4 A. Well, a whole variety of issues. Right now we 5 have a research project to see the viewpoint of the members on 6 medication treatment and psychotherapy treatment and the 7 balance between the two. That's our current research project. 8 Q. And is that ongoing? 9 A. Yes. It's ongoing. 10 Q. Are you on the editorial boards or are you a 11 peer review editor for any publications or journals, Doctor 12 Breggin? 13 A. Yes. I'm a peer reviewer on several journals. 14 The way a peer review works is that when you submit an article 15 to a journal, if it's a peer review journal, a peer meaning 16 your colleagues or equals, review the article, give opinions 17 on it before it's accepted for publication or rejected for 18 publication. So professionals on various journals make up a 19 panel in a sense or a committee in a sense of reviewers, and I 20 am a reviewer of four, five or six journals. 21 Q. International Journal of Risk and Safety in 22 Medicine? 23 A. Yes, sir. 24 Q. Review of Existential Psychology and Psychiatry? 25 A. Yes, sir. 9 1 Q. What does existential mean? I've seen that a 2 lot. 3 A. Existential means with emphasis on human values 4 and human ethics and the role that values and ethics and 5 ideals play in mental health. 6 Q. The Psychotherapy Patient. What is that? You 7 are on the editorial board of that publication? 8 A. That's a journal that four times a year or so, 9 actually it's a little less frequently, puts out a volume of 10 research on a topic in psychotherapy. For example, sometime 11 in the next year -- it should be coming out soon -- I'll be 12 actually editing one of the volumes, actually the work's been 13 done. And that particular volume will be on working with very 14 disturbed or upset patients and I'll be editing that 15 particular volume. 16 Q. Have you during your practice, since we're 17 talking about disturbed and upset patients -- and certainly 18 Mr. Wesbecker presents a picture of that, does he not, sir? 19 A. At different times he does; at other times he 20 does not. I mean, there's vast periods of time when he does 21 not appear that way. 22 Q. But have you in your experience had one-on-one 23 dealings with patients who are disturbed and upset? 24 A. Yes. It's in a way a specialty of mine to do 25 that. It's just evolved over the years by people coming to me 10 1 and being referred to me for that purpose. That's one of the 2 reasons why I'm doing the special -- editing the special 3 volume on working with disturbed patients, and I give 4 workshops to psychiatrists, psychologists, mental health 5 professionals on how to do that. 6 Q. I see here you're also on the editorial board of 7 The Psychotherapy Patient. What is that, sir? 8 A. I think you just asked me about that one. That 9 was the one I was talking about where I have the volume coming 10 out in the next year. 11 Q. I'm sorry. I need to be checking these off as 12 we go. How about the publication, Changes in International 13 Journal of Psychology and Psychotherapy? 14 A. Yes. Changes is the official journal of the 15 major psychotherapy association in Great Britain, and I am on 16 that board; yes, sir. 17 Q. Reviewing articles that are being submitted by 18 other psychiatrists and psychotherapists for publication in 19 that journal; is that correct? 20 A. Yes. Reviewing. Also discussing in general 21 with the editor about directions the journal might take and 22 contributing to it, as well. 23 Q. I see that you're also involved in the Journal 24 of Mind and Behavior. Can you identify that, sir? 25 A. The Journal of Mind and Behavior is a very 11 1 research-oriented journal and I do the same thing there. I'm 2 on the editorial board and I'm published in it, too. 3 Q. And I see also listed the Journal of Hospital 4 and Community Psychiatry. What is that publication, sir? 5 A. That's a publication of the American Psychiatric 6 Association that deals with -- often with the more disturbed 7 population, and I'm a reviewer. That means occasionally they 8 send me an article to look at and to give an opinion on for 9 publication. 10 Q. In addition to serving as a member of various 11 editorial and peer review positions, have you given 12 professional seminars, lectures and papers, Doctor Breggin? 13 A. Yes, I have. 14 Q. And give us a rundown of some of the places that 15 you've given seminars and presented papers. 16 A. Well, just to organize it, I started with my own 17 home area. I've given talks at the University of Maryland 18 psychiatric center. These are usually -- most of these are 19 seminars where doctors, nurses, psychologists can get 20 professional training credit by having an outside person come 21 in and give a talk and some of them are just invited without 22 that, but often they have that credit training program flavor 23 to them. But I've given that kind of presentation at the 24 University of Maryland psychiatric facility, at two or three 25 local state mental hospitals, Saint Elizabeth's Hospital, very 12 1 famous place, on several occasions. Also given grand rounds 2 at these places; that's where you're invited in as the outside 3 doctor or sometimes the inside doctor to review a case or to 4 review a subject for the doctors present. I've done that at 5 Saint Elizabeth's, at Suburban Hospital. I've given talks at 6 the Walter Reed Army Hospital psychiatric training program. 7 Q. Walter Reed, is that -- 8 A. That's the big army medical facility in 9 Washington. We have a number of those, and just looking at 10 where I talk locally, it's been at most of those places. I've 11 given invited presentations to the National Institutes of 12 Health, National Institute of Mental Health, National 13 Institute of Neurological Disease and Stroke, although that 14 one's gone back a few years. A variety of different medical 15 places. And also many universities. Johns Hopkins, not long 16 ago, the health students invited me to give a talk. Harvard 17 University. A lot of places around the country. 18 Q. How about Georgetown University School of 19 Medicine? 20 A. I've given a number of talks there, as well. I 21 don't want to give the impression that's what I do all the 22 time; that's spread out over a number of years. 23 Q. You're not currently speaking at all of those 24 places and here at once, are you? 25 A. Right. 13 1 Q. Anything else about your education and training 2 on what you've done, Doctor Breggin, in your field of medicine 3 that you think would be helpful to the jury in understanding 4 your credentials and where you're coming from here, sir? 5 A. I think the only thing I can think of off the 6 top of my head is that the kind of presentation I've been 7 giving you is actually quite similar to one that I've given 8 many times to professionals, as well, often using the same 9 simplified language, sometimes more complex. So it is 10 something I'm familiar with doing. The reason why I may be 11 able to appear to do it with relative ease is because I've 12 done it before professional audiences in so many occasions. 13 Q. In connection with reuptake, the serotonin 14 system and specific serotonin reuptake inhibiting? 15 A. Yes. And also a variety of other medications, 16 as well. 17 Q. Have you published medical books, Doctor 18 Breggin? 19 A. Yes, sir. 20 Q. Tell us about -- just give us a list of a few of 21 the books you've published concerning psychiatry or medicine. 22 A. My first two medical books -- well, my first 23 goes back to -- well, actually back to college, really I 24 mentioned to you from the mental hospital program, we did 25 publish a book that was published as a professional book about 14 1 the volunteer program but my -- that was co-authored. In '79 2 I published a book on the brain dysfunction associated with 3 electroshock treatment. Then in 1983, I published a book on 4 psychiatric medication, both of these by Springer Publishing 5 Company, which is a professional publisher, not a lay 6 publisher. 7 Q. In addition, I've published several books which 8 are crossover books, that is, they're intended for both 9 professional audiences and lay audiences. Toxic Psychiatry is 10 an overview of all psychiatric medications from a scientific 11 viewpoint, but also from my own philosophy, which is that they 12 are often overused or more hazardous than we realize. That 13 book is in the general bookstores, but it's also listed as a 14 basic medical textbook at the National Library of Medicine, 15 and it's been a selection of the professional book club. So 16 in recent years, I've written several books like that which 17 are read by the general public but also are in professional 18 book clubs or used in courses, often introductory courses in 19 psychology, for example, or in abnormal behavior at different 20 universities. 21 Q. How about Talking Back to Prozac? 22 A. That's one of my more recent books. That was 23 co-authored with my wife. I actually did the writing, but she 24 has done so much on the maintenance of the files and helping 25 with research. She's not a professional person, but she's 15 1 such an integral part of the whole organization of my life 2 that she's been co-author of the last two books that I've 3 written. And Talking Back to Prozac was definitely written 4 for the general audience, but it too has been a selection now 5 of the Psychotherapy Book Club, which is a professional book 6 club. So, again, as kind of a crossover. I'm trying to write 7 books that are understandable to both professionals and the 8 public. 9 Q. Have you written a book since Talking About 10 Prozac? 11 A. Our most recent book, yes, is about some 12 government programs that we've been critical of called The War 13 Against Children. We're very critical of the overmedication 14 of children. It's a very big concern of mine that too many 15 children in America are being medicated. 16 Q. Well, let's make it clear, Doctor Breggin, you 17 have as a philosophy criticism of the administration of 18 psychiatric drugs generally, and specifically you have some 19 criticisms in connection with fluoxetine hydrochloride, 20 Prozac; is that correct? 21 A. Yeah. I'm trying to separate out my general 22 philosophy from the very specifics of this particular 23 medication. This is the only time I've written a book, one 24 book about one medication, for example. And while, in 25 general, I myself prefer not to treat people with medication, 16 1 I certainly think it's one of the options that people should 2 have. And there's many, many doctors, of course, providing 3 that medication, providing medications, but I do separate out 4 my general feeling about medication from the specific 5 criticisms or analysis here today of Prozac. 6 Q. All right. Now, I think it might be helpful, 7 Doctor Breggin, if we do a quick review of this serotonin 8 system generally and reuptake in this -- where it works in the 9 synaptic cleft specifically. 10 A. All right. 11 Q. And I'm not going to put this on the easel, but 12 just to refer back to this diagram of the brain. 13 A. Should I come on down again? I guess I have to, 14 don't I? Okay. 15 Q. You talked about the serotonin system affecting 16 a number of different areas of the brain; is that right? 17 A. Yes. What I pointed out is that the beginning 18 of the cell, the body of the serotonin cells are clustered in 19 several clusters here that are in the dark color called the 20 raphe nuclei and that that's where it starts, but then the 21 long arm or axon of each individual cell reaches sometimes 22 into the spinal cord a shorter distance into the cerebellum 23 and on up in particular into the centers of the brain that 24 have to do with mental life and emotional life, and they 25 spread throughout and through that, develop elaborate, 17 1 elaborate, elaborate connections, somewhat kind of like the 2 complex roots of a tree with the fibers. You can see -- if 3 you've taken out a tree from a transplant, you see all the 4 branches of the fibers and the same process happens here 5 throughout the brain. It's a system that we don't even begin 6 to understand what it's doing all these many places in the 7 brain. We have very, very little understanding of what it's 8 doing. We know that it can, to some extent, regulate the 9 pituitary functions and therefore the glandular functions of 10 the body. We know it's influencing the areas that have a lot 11 to do with motion and thinking, but it's all in a very general 12 way. We have no specific knowledge that in this part of the 13 brain it affects this nerve and that affects visualization or 14 thinking certain kinds of thoughts or having certain kinds of 15 feelings. We have no such knowledge like that. It's much too 16 widespread. It's the part I used in the analogy. It's part 17 of the orchestra of the brain and we're not able to decipher 18 what particular tunes it's playing, what in particular it's 19 doing. 20 Q. Now, again, is it true that the serotonin system 21 that you've depicted here is only one of dozens of 22 neurotransmitter systems within our brain? 23 A. Yes. And one of about six or eight that has 24 been studied very, very extensively and we're only beginning 25 to get a sense of, we really don't have a -- we don't know how 18 1 our brain relates to thought and to feeling. It's still a 2 very enormous mystery. 3 Now, one very basic theory that's important is 4 that the system has something to do with the regulation of 5 impulses. 6 Q. All right. Is that generally accepted? 7 A. That is generally accepted and was the basis of 8 exploring Prozac, exploring a whole variety of substances that 9 eventually became Prozac. The theory is that this system 10 regulates our control of impulses and, in particular, either 11 violent impulses towards others or toward self, and that this 12 is one package physiologically that violence towards self and 13 others is a single entity that has a lot to do with this 14 system. And one of the reasons that's thought to be so is 15 that the by-products of this system, the by-products which we 16 attempt to measure to see how active the system is, the system 17 appears to be sluggish or slow, not putting out as much waste, 18 as much product in some people who are violent or suicidal or 19 delinquent. And this has been done in studies of children, 20 adults and a variety of animals and, in particular, rhesus 21 monkeys. 22 Q. Are these by-products, is that what has earlier 23 been referred to as metabolites? 24 A. Metabolites, yes. Metabolites. The major 25 metabolite is called 5-hydroxyindoleacetic acid, not something 19 1 you have to remember, and it's measured generally in the 2 spinal fluid, which is a fluid that encases the brain. That's 3 a very rough measure. 4 Q. Why? 5 A. In a way, it's like measuring the exhaust of a 6 car to try to figure out how hard the engine is working and 7 how fast it's going, when there are so many things that can 8 control the car, the catalytic converter, for example. Unlike 9 the car, the brain itself is using up some of the products and 10 they aren't even getting into the spinal fluid, so it's a very 11 indirect measure, but there's been hundreds of articles, 12 suggest -- sometimes supporting the view, sometimes not, but 13 hundreds of articles that tend to suggest that in some people 14 this system is low, sluggish, whatever term to describe that, 15 less active when people are lacking in impulse control. And, 16 again, it's a unitary idea. It's violence and suicide, it's 17 not just one or the other. 18 Q. You know, Doctor -- 19 A. Let me take the other end for a second. The 20 other end is there's a lot of information of what happens when 21 the system is jacked up too high so disruption of its being up 22 or down is likely to cause impulse control problems, and 23 Prozac's overall tendency is to increase the output of the -- 24 the activity of the system, increase the activity of the 25 system, and that is what probably -- and there's general 20 1 agreement on this -- produces the agitation, the 2 hyperactivity, the overstimulation, that irritability, that 3 whole agitation syndrome. And some people think that when the 4 system is hyperactive it tends to produce anxiety and upset 5 and agitation and when it's low it tends to produce 6 depression, but all of this is I would say hypothetical. It's 7 the beginning attempts, very rudimentary attempts to 8 understanding it. We can say the consensus is this system has 9 to do with impulse control. 10 Q. Would that include depression and feelings of 11 lows and high? 12 A. Definitely. 13 Q. All right. Specifically -- let's get this easel 14 because I'm getting tired of holding these charts -- let's 15 look at how Prozac works in connection with, as you say, 16 affecting or jacking up the sluggish system. Now, is that 17 what it was intended to do? 18 A. Yeah. The intention -- the theory is that 19 depressed people may have a sluggish system and so we're going 20 to energize it, energize the system with Prozac. It's not a 21 scientific fact and, in fact, when a person is depressed and 22 comes to the psychiatrist's office, it's not like you're a 23 diabetic and the doctor says, "Hey, your blood sugar is way 24 up, we'll give you some insulin and lower it," it's a 25 hypothesis, a theory, an idea that the depressed person may 21 1 have a low serotonin. It's not something the doctor measures 2 and then gives the right amount of Prozac for. It's just a 3 theory. The doctor gives the Prozac which is digested and 4 then passed through the blood, passed through the liver, 5 eventually getting into the brain in amounts that aren't easy 6 to calculate with no known knowledge whatsoever in that 7 particular patient of what's happening here. So it's not like 8 getting a blood sugar level and adjusting it with insulin. 9 It's a much vaguer, more hypothetical process than that. 10 Q. All right. Why don't you take us through -- and 11 you described it generally yesterday, why don't you take us 12 through again how this -- the anatomy of this, Number One, and 13 then how the -- I've got some better colors, if you'd like. 14 We have black, white, purple. 15 A. We'll try this. This is your basic neuron or 16 nerve cell. Here's its body in biology. You remember I 17 mentioned yesterday it has a nucleus in it and other things in 18 the cell, and this is the long arm or axon and it, too, breaks 19 down into fibers and this is rather infinite. I mean, you get 20 a lot of fibrousness as you look at it under a microscope. It 21 literally looks like the fine hairs on a -- the roots of a 22 tree just spreading everywhere and this is one of the tips, 23 one of the tips of these fibers, and this is the blowup -- 24 this footlike structure is the blowup of this. Is that clear, 25 I hope? This footlike structure, which is one of hundreds or 22 1 more at the end of the cell, is what's blown up here. 2 Now, this particular cell is producing 3 serotonin, which I have labeled as S. And the cell has an 4 impulse, an electrical impulse coming down it and it releases 5 the serotonin into this little tiny, tiny space called the 6 synaptic cleft or synapse, and then the serotonin to be 7 effective has to reach the receivers here on the surface, and 8 they're called receptors. It has to reach and fit. And only 9 serotonin fits. 10 Now, Mr. Smith asked me yesterday if there could 11 be other things in here and I said, well, we don't really -- 12 we think of this synapse as the serotonin synapse, but there 13 could be other things passing through. There could be some 14 other neurotransmitter passing through in this fluid system, 15 there's no walls here. It wouldn't connect. It wouldn't have 16 the effect. But there are no walls here. It's reaching out 17 into the network of the brain. When the serotonin reaches 18 here it fires the nerve impulse of the next nerve. The whole 19 process, serotonergic neurotransmission, the whole process is 20 what Prozac aims to increase on the hypothetical idea that it 21 might be low in some people. 22 Q. And, again, we don't know in any particular 23 individual whether it's high, average or low? 24 A. No. We don't know if it's high, average or low 25 and we don't even know if 50 years from now science will think 23 1 it's a correct theory, because there have been many similar 2 theories over the years that no one now believes is correct. 3 Q. Give us an example of that. That's interesting. 4 A. Well, it was thought for a long time that people 5 with depression had something the matter with their steroidal 6 system, what's called the corticosteroids. And there was a 7 fancy test to see if the brain was reacting right. And it was 8 generally accepted for a long time that this probably played a 9 role in causing depression. It turns out that it's much more 10 an effect of being stressed, so people who have head injury 11 have it, people who are stressed have it physically, people 12 who are depressed sometimes have it. So it hasn't turned out 13 to be a cause, but rather a result of many different kinds of 14 stresses. 15 In medical school, the research that I carried 16 on had to do with the production of adrenaline during anxiety, 17 and one of the questions I researched was did the output of 18 adrenaline at all cause anxiety or was it a result of anxiety 19 and, of course, it's basically a result. If you're anxious 20 you put out adrenaline, it makes you sweat, it makes your 21 pupils get big, so it gets you ready to do something. It 22 scares you, gets you alerted, but it's not the cause. And 23 it's not established that having low 5-hydroxyindoleacetic 24 acid is a cause, although that is a very widely-believed 25 theory right now. But I've been around for 30 years and I've 24 1 seen a lot of widely believed theories. 2 Q. You mean you've been in medical practice for 30 3 years? 4 A. Yes. 5 Q. You're not 30 years old, are you? 6 A. I've been interested in the psychiatric 7 literature since 1954 or '-5, and there's always been a theory 8 and this is the one now. On the other hand, it does seem that 9 this system probably has something to do with impulse control 10 and my own sense of it is the disruption of this system 11 disrupts impulse control, can make it harder to control 12 impulses, that that's very, very possibly true. 13 Now, one of the things that we discussed is how 14 does Prozac work. Prozac does not stimulate this system 15 directly. Fluoxetine does not directly come in and replace 16 the serotonin and stimulate the system; there are drugs that 17 do that but the serotonin does not do that. What serotonin 18 does is block the removal -- and here we see one of the 19 serotonin molecules being taken up to a chemical transporting 20 system made of chemicals and it's transporting the serotonin 21 back in the cell. That process then allows itself to either 22 reuse the serotonin or to break it down into 23 5-hydroxyindoleacetic acid. Now, the theory that the 24 researchers at Lilly developed and worked out was that if they 25 could block the transport system, you'd have more serotonin 25 1 for a longer period of time, even without producing more you'd 2 have more because it wasn't being removed by the shuttle. And 3 I gave you the analogy yesterday of the boxcars. I think of 4 these chain systems that carry stone up a quarry, and imagine 5 that they're competing to see whether the red stones are 6 getting in or whether the Prozac's getting in. And if Prozac 7 is getting into the transport system then there isn't enough 8 room for the serotonin, and that's not too much of an 9 oversimplification. I mean, that's basically what's going on 10 that the Prozac gets into the transport system, uses it and 11 the serotonin stays in here and the measured results -- and 12 this is measured in a variety of ways -- is that in general 13 these nerves start firing more, but it's very complicated 14 abuse; the neuron doesn't like this. This is an intrusion. 15 Q. When you say it's an intrusion, what do you 16 mean? 17 A. The brain was not intended to have Prozac in it. 18 Q. Otherwise, the good Lord would have made Prozac? 19 A. The same with alcohol, the same with many 20 different things that people do with their brains. The brain, 21 in every case just about that we know of, resists a substance 22 coming in, even a natural substance, which Prozac is not, if 23 it's in excess the brain tries to get rid of it. The brain 24 has a process called homeostasis; it's trying to get back to 25 normal. 26 1 Q. Is this controversial? Is this disputed by 2 Lilly? 3 A. I certainly don't think that Lilly could dispute 4 that the brain is trying for homeostasis. What Lilly would 5 dispute, they would say it is good for the brain to have this 6 activity increased; whereas, I would say if the brain thought 7 so it would have done it, but this is an intrusion. So they 8 call it enhancement of neurotransmission because they believe 9 this is a good thing and I view it as a hyperactivity of this 10 system that's unnatural. And the question is does that 11 unnatural hyperactivity sometimes make people feel better? 12 That may be. There are many things that people do that make 13 them feel better by making a system hyperactive. You can do 14 it with other drugs that are more commonly known as 15 stimulants, like amphetamines will make the system hyper. 16 Even make this one a little hyper, not as hyper as Prozac 17 makes it. 18 Q. Why? Why does Prozac cause such sensitivity 19 here? 20 A. Because the drug was so cleverly designed to 21 specifically get at this system. They worked till they got a 22 drug that was pretty specific for this system. Now you'll -- 23 for that reason they call it a selective reuptake blocker or a 24 selective blocker for just this nerve, but it's much more 25 complex than that because once this nerve gets hyperactive 27 1 other nerves react back, so you get reactions in the dopamine 2 systems, you get reactions in the norepinephrine system, and 3 you get reactions in this system as it tries to shut down the 4 hyperactivity. And to try to shut down the hyperactivity it 5 does two things that we know of. I should always put that in. 6 We may find years from now it does one hundred things, but we 7 know of two that it does right now. And Lilly, because 8 they're the lab that works on this, has done some of the 9 research, but it's been done all over the western world and 10 elsewhere in the world. 11 One of the things that happens is that the very 12 first dose -- and this was known by Lilly from the 13 beginning -- the first dose of Prozac, this never shuts down, 14 it stops releasing serotonin. 15 Q. Why? 16 A. Because it has sensed from another feedback 17 mechanism that's not drawing here, there's another feedback 18 mechanism. It senses that there's too much out here. It 19 senses it's not being removed. 20 Q. Do you mean it recognizes the change? 21 A. It recognizes the excess of serotonin. That's 22 indisputable. That's as close as we get to scientific fact in 23 some of what we're talking about. It recognizes there's too 24 much serotonin, so it stops firing. It stops releasing as 25 much serotonin and may even go to a relative almost total 28 1 shutdown for a while. 2 After a time, however, this system just can't 3 hold up and it stops functioning in that manner over a period 4 of a week or two. It begins to gradually stop controlling 5 this nerve. But very quickly, not as sharply and 6 dramatically, but very quickly within days another slower 7 process begins as the nerve again tries to handle what it 8 perceives to be as too much serotonin. And what it does is 9 these receptors begin to disappear. No one knows exactly 10 where they go. No one knows if they're in essence dead or if 11 they've simply turned in a fashion that inactivates them, but 12 they are no longer measurable. They don't exist. And this 13 has been demonstrated on some of -- there are classes of these 14 receptors, some classes but not others. In other words, you 15 might do a chemical study of how much one of the receptor 16 classes is present, you may find 30 to 60 percent of it, 40 17 percent of it is gone, it isn't there anymore. 18 Q. Is that a study you did? 19 A. No. That requires being in a laboratory. These 20 are studies done at Lilly and other places in Canada and North 21 America. 22 Q. All right. 23 A. And these are facts. This is in the factual 24 area that we have a shutdown mechanism here and we have this 25 which is called subsensitivity, it becomes less sensitive. So 29 1 what happens to the patient who takes Prozac is complicated, I 2 think, beyond our ability to predict, really complicated 3 because you have the system doing different things. Now, most 4 measures show that the system is getting more active despite 5 the attempts to shut it down, that Prozac is so powerful that 6 if you measure the activity of these nerves, which you can 7 actually do directly electrically, you can put in a measuring 8 electrode and do it other ways, do it indirectly by what the 9 system is doing, what it's putting out, that this system as a 10 whole is getting hyperactive. And Lilly would call it 11 enhanced. At the same time, we don't know if it's going down 12 in some places, whether some places -- because the brain is so 13 complex -- the compensation is stronger than the Prozac. But 14 the overall effect generally seems to be the hyperactivity 15 production and that's what is responsible, surely responsible 16 for the anxiety, the tension, the insomnia, this whole complex 17 of things that are stimulant in nature. That is produced by 18 this excess of serotonin making this system go. And in the 19 extreme, it produces a degree of stimulation which is 20 psychotic in level, that is, the person loses touch with 21 reality. They're so overstimulated they may think that 22 they're God or may think they're some incredible person, know 23 incredible people. Typically, when someone is that high they 24 may take off their clothes and run outside and try to direct 25 traffic. And that happened on these studies. On just the 30 1 short-term patients four, five weeks or so, this happened in 2 approximately 1 out of 100 people got that high. 3 Q. Why -- if you have this hyperstimulation, why 4 doesn't everybody react the same way every time all the time, 5 Doctor Breggin? Is that a reasonable question? 6 A. Well, it's a reasonable question and it plays 7 some role in this suit because he, this gentleman, Mr. 8 Wesbecker got Prozac twice. One of the questions that's 9 raised is he seemingly got fatigued the first time he took it 10 and then seemingly agitated, I think obviously agitated the 11 second time he took it, in the Doctor's opinion or 12 observations. Well, there's many reasons that can happen. In 13 this case we don't need the complicated reasons because I 14 looked over the chart and it's very simple what happened the 15 first time. It's really simple why he got fatigued. He was 16 toxic on lithium. At the moment that he is experiencing 17 himself as fatigued, the Doctor has discovered he has a serum 18 level of 1.5 milliequivalence of lithium, which is a generally 19 acknowledged toxic level. And the Doctor calls him on the 20 phone, this is in the middle of his taking Prozac the first 21 time. The Doctor calls him on the phone and says, "Your 22 lithium is up, your level is up." He says -- he wonders if he 23 took the test at the wrong time of day. That is, whether he 24 through a complicated -- you're not supposed to have your 25 lithium the morning you take the blood level; you're supposed 31 1 to skip the morning and check the blood level. He asked him 2 did you skip the morning, he wasn't sure because he had such a 3 high level on the test. So the Doctor says cut back on your 4 lithium. 5 Q. And I want you to get into that in some detail 6 later, Doctor Breggin. My question simply was: If you have 7 this definitely, I mean, in every neuron you're going to have 8 by virtue of the intake of Prozac an increase in the serotonin 9 availability or volume in the synaptic cleft, if this is bad, 10 why isn't it bad for everybody? 11 A. There are many reasons why people react 12 differently, why some people feel good and some people feel 13 bad on a drug, and often we don't know the answer. In this 14 case it turned out to be another drug he was taking that was 15 probably making him fatigued, not the Prozac. But if you 16 think about diabetes, which many of us have some familiarity 17 with that, a person is taking a certain number of insulin 18 units a day, one day that produces low blood sugar, another 19 day it's not enough and the blood sugar is too high. So even 20 in a very gross system like the pancreas attempting to control 21 the blood sugar, which is a much more gross system than this, 22 this is like the fine tuning of human life, whereas insulin, 23 animals, everybody shares that kind of a system, they don't 24 have the complexity of this brain system. So even in a system 25 as comparatively rough as the insulin system, the doctor who's 32 1 studying the blood sugar can't always know how much insulin is 2 going to do it on any given day. 3 Q. Even when he can measure it? 4 A. Even when he can measure it. Even when the 5 patient is walking around with insulin testing kits now. You 6 may have friends who before they eat, after they eat are 7 taking a little blood or testing their insulin. They're 8 testing their blood sugar. I took the same amount of insulin 9 today, but it's up. Why would that happen. There are so many 10 reasons. 11 In the case of Prozac it's even more complex 12 than insulin because Prozac is a pill, so it's got to go 13 through the stomach; it's got to be digested; it's got to go 14 in the bloodstream indirectly; it's got to pass through the 15 liver, and what the liver does to it will determine how much 16 of it is put out, and this system, unlike most brain systems, 17 also responds to how much of the building blocks are 18 available. 19 The building block, the serotonin is something 20 you may have heard of because it's a basic amino acid called 21 tryptophan. It's something that you used to be able to buy on 22 the market till there was a bad batch of it in Japan. The 23 amount of the food substance that's available affects 24 production in the system. Usually these systems protect 25 themselves from the vagaries of how much you ate that day, but 33 1 this system is responsive to that. 2 There are just a whole variety of things. Your 3 mood, your attitude will affect your brain, so it's very 4 common for people to react differently one time when they get 5 a psychiatric drug and another time when they get it. And, of 6 course, the second time a person gets it the brain has had 7 experience with it once, so maybe the brain is set differently 8 and waiting differently for the effect of the drug, but it is 9 very, very common for a person to respond differently to 10 insulin, to alcohol, to any substance that affects the brain 11 in the body. But in this case, as I said, we don't have to 12 get that complicated because when I look at the record, he was 13 getting a drug in toxic dose that would make him fatigued at 14 that moment, and that was cut back and we can go into that 15 with the dates and all that later. 16 Q. Do you think there's anything else that's 17 relevant that we need to know about the serotonin system, the 18 synaptic interchange and this reuptake blocking of serotonin 19 by Prozac? 20 A. Well, just to reemphasize, the general idea that 21 it is impulse controlled, that this has something -- I'm sure 22 it does many other things. I've already told you it helps 23 control the pituitary and that when it goes up that it 24 produces anxiety, agitation, mania and those things can be 25 accompanied by violence. We know that mania, agitation can be 34 1 accompanied by violence and sometimes by suicide, and then 2 when it goes down, it's more like depression. That's a 3 general theory. But really at this point I'd say this: 4 Systems involved with impulse control, disrupting it disrupts 5 impulse control. 6 Q. Okay. Let's get into more specifics of what 7 you've done and what you've reviewed. 8 A. Okay. 9 Q. Let me begin, Doctor Breggin, by asking you what 10 you did to -- I assume you have some opinions in this case? 11 A. Yes, sir. 12 Q. What did you do to -- what did you review to 13 formulate your opinions in this case? 14 A. I reviewed masses of materials. I have many, 15 many, many cartons, cartons of materials that I reviewed. One 16 whole batch of a number of cartons and microfiche are 17 materials I obtained from the Food and Drug Administration of 18 the United States, the FDA, and I obtained them directly 19 through something called FOIA, the Freedom of Information Act. 20 It entitles any citizen, you could do this, anyone can do 21 this, to write to the government and say, "I want basic 22 information about the inner workings, paper work of your 23 agency on a particular subject. I want the paper work in this 24 case on the approval process of Prozac." Now, if you wrote 25 them that they might write back and say, "We have hundreds of 35 1 cartons of material on that. What particular do you want on 2 Prozac?" So I would send in individual requests on material 3 on Prozac, and that and the Prozac approval process. And I 4 did that on my own before, actually, I became involved as an 5 expert in this case and then afterward, as well. 6 Then in addition, Mr. Smith had -- and his 7 colleagues had gathered information from the Food and Drug 8 Administration, too, and you shared that with me, although, I 9 think I probably had more volumes of that. In addition, Mr. 10 Smith obtained information from the corporation, from Eli 11 Lilly, cartons and cartons of information, and he sent me 12 large batches of that material, memos, research, letters, all 13 kinds of things surrounding the internal process at Lilly. So 14 I had fairly good coverage of the processes at Lilly during 15 approval of the drug and the processes of the FDA during 16 approval of the drug. 17 In addition, over the years I have gone to 18 conferences sponsored by Lilly in which it has people speaking 19 on the subject of medication and Prozac, and recently I went 20 to what I think is the first FDA full-day training program for 21 physicians and other people to understand -- and industry to 22 understand the postmarketing evaluation of drugs, the 23 evaluation of drugs after they're already approved. I have 24 interviewed a number of FDA officials over the years and 25 former officials as to how the Food and Drug Administration 36 1 works. 2 Q. Okay. You've interviewed FDA officials 3 generally on the approval process, but have you talked with 4 FDA officials specifically in connection with the approval of 5 Prozac, Doctor Breggin? 6 A. Yes. I've spoken with them both generally as to 7 how the FDA works and specifically about the approval process 8 for Prozac. 9 Q. How were you able to do that? We weren't able 10 to talk with or take the depositions of any FDA employees in 11 this case, not a one. It was disallowed by law for us to do 12 that. 13 A. Well, I wasn't involved in the case at that time 14 with you, and I just called people. I said, "Hi, I'm Peter 15 Breggin, I'm a psychiatrist here in Bethesda. You may know 16 about my work generally." I got a general acknowledgment that 17 they either heard my name or at least in one case specifically 18 familiar with things I had done, and then I went in one case 19 and I had extensive interviews with the man who was in charge 20 of the study of Prozac's side effects. His name is Richard 21 Kapit, and he was no longer with the FDA at the time, although 22 he's back there now, he was with another government agency. 23 And he and I sat and talked for a few hours specifically about 24 Prozac. And he was the key person in all of the FDA I wanted 25 to talk to because he wrote the evaluations, the summary 37 1 evaluations of adverse reactions to Prozac. 2 There are two basic reviewers for any drug, one 3 reviewer inside the FDA looks at all of the studies on 4 efficacy, on whether the drug works. Then another reviewer 5 looks at all the studies on what the dangers of the drug are 6 and that was Kapit, and he was very important because he was 7 in basic agreement with me that this drug is like a stimulant. 8 He himself, in fact, in his reports had compared it to 9 amphetamine, the classic amphetamine stimulant and I had 10 already concluded the same. It was very, very good to be able 11 to talk with him about that. I also talked to a couple of his 12 bosses and other people on the telephone. He was the one 13 lengthy face-to-face interview. I just called people, they 14 talked to me. That's almost always been the case. 15 Then I had the depositions of a number of the 16 Lilly employees, so when an attorney would interview the Lilly 17 employee, such as Doctor Heiligenstein or Doctor Beasley, I 18 would then have the opportunity to read, study, what the Lilly 19 employees said. 20 Q. For instance, Doctor Breggin, we've read 21 portions of the deposition of Doctor Fuller, portions of the 22 depositions of Doctor Stark and Doctor Slater. Have you read 23 those same depositions? 24 A. Yes. Doctor Wong. I mean, there was quite a 25 number, and others, as well. 38 1 Q. All right. 2 A. Including the experts. 3 Q. What do you mean, the experts? 4 A. Three or four of the experts. 5 Q. The experts that Lilly designated in this case? 6 A. Lilly designated, yes, and also two experts that 7 you designated. I read one of their depositions, one of the 8 two experts' depositions. 9 Q. Okay. 10 A. Then I read the family member depositions, which 11 are quite large, and skimmed or read various other 12 depositions. Read carefully, in particular, James' deposition 13 because he was one of the few people who actually spent some 14 time -- his son James, who spent some time with him right 15 around when he was getting agitated on Prozac; and I read 16 James Lucas, the friend, I read his deposition carefully; and 17 the diary of his wife, the people who were right there at the 18 moment. 19 Then I had a number of important depositions, 20 several different depositions that Doctor Coleman gave 21 because, again, I wanted to see what did the person who was 22 there and who knew the most and was the most skilled and 23 trained, what did he observe at the time. 24 Then -- I mean, there's so much I literally need 25 notes to keep track of it all. The medical records. I read 39 1 all the medical records that were made available to me and 2 they at least covered his -- the psychiatrists he saw and his 3 three psychiatric hospitalizations and a variety of other 4 materials, and they were the complete records as far as I 5 could tell. Then there was a coroner's inquest. After the 6 death, the coroner got together -- 7 MR. STOPHER: May we approach the bench, Your 8 Honor? 9 (BENCH DISCUSSION) 10 JUDGE POTTER: You-all have to decide who's 11 going to speak for Lilly on this witness. 12 MR. FREEMAN: I will. 13 JUDGE POTTER: All right. Okay. 14 MR. STOPHER: I apologize, Your Honor. 15 JUDGE POTTER: That's all right. It just works 16 better. 17 MR. FREEMAN: We object to this line of 18 testimony in that the Court has previously ruled out anything 19 in connection with the coroner's inquest or anything of that 20 kind, particularly the finding that I anticipate he's going to 21 get into. 22 MR. SMITH: I just was trying to get him to 23 identify what he'd read and, obviously, there's a transcript 24 of that. 25 JUDGE POTTER: As long as he just said he's read 40 1 witness's testimony or whatever, then the objection is 2 overruled. 3 (BENCH DISCUSSION CONCLUDED) 4 Q. All right. You've told us about reading 5 testimony from the coroner's inquest. Anything else you did 6 in connection with reviewing the facts of this case to form 7 opinions? 8 A. Yeah. The coroner's inquest was important 9 because we got -- 10 Q. That's all we want to say about the coroner's 11 inquest. 12 A. Yes, sir. Looked at -- over the years I've 13 looked at the FDA regulations. I went over them a little bit, 14 not for this particular moment, but I've seen them over the 15 years. I've read over the years and for this case a number of 16 the FDA's advisory committee meetings. The FDA has an outside 17 advisory committee of experts that itself is appointed by the 18 FDA, it has no power, the committee, but it makes 19 recommendations to the FDA. It makes a recommendation of 20 whether to approve a drug or not after the information is 21 submitted to it, for example, and I read two of the FDA 22 committee meetings pertinent to Prozac. I reviewed some 23 others out of interest to do some comparisons in my own mind 24 on others that I had in my possession for other medications. 25 Q. Specifically, Doctor Breggin, did you look at 41 1 the September 1991 PDAC committee transcript? 2 A. Yes, I did. 3 Q. All right. Go ahead. I've interrupted you 4 about three times now. 5 A. I read some of the trial testimony, Lilly pieces 6 of the trial testimony here, I think. Did you give me some of 7 that? 8 Q. I think so. 9 A. And that's -- that's the basic materials I went 10 over, and I don't know if I mentioned scientific literature, 11 books, treatises, that's an ongoing process with me. 12 Q. Did you go back specifically and review what you 13 considered all of the pertinent scientific literature in 14 connection with the serotonin system, Prozac, around matters 15 that would be of scientific importance in formulating your 16 opinion in this case? 17 A. Well, I don't think any human being could read 18 all the pertinent literature in a sense because the literature 19 on Prozac and related issues, like impulse control, is huge, 20 but I did review hundreds of articles in the last year, 21 hundreds and hundreds, maybe into the thousands of articles to 22 one degree or another relevant to this issue in the past 23 couple of years. 24 Q. All right. Can you give the jury an estimate of 25 the amount of time you spent studying this case and studying 42 1 Prozac to come to conclusions in this case, Doctor Breggin? 2 A. Well, because of center reports I've been doing 3 and other writings and this case and other -- 4 Q. I'm talking about this case. 5 A. Just this case it is -- oh, it's certainly 6 hundreds, I would guess. 7 Q. Hundreds of hours? 8 A. Must be by now. I don't have a real good count 9 in my head. It's a lot, a lot of hours, a lot, a lot of time. 10 Q. Can you give the jury any estimate of how many 11 documents you reviewed? 12 A. I would say thousands. 13 Q. In connection with this case? 14 A. I would say thousands. 15 Q. Based on the time that you spent reviewing these 16 documents, based on your years of experience as a psychiatrist 17 who sees and treats people and based on your experience as 18 training as a medical doctor and specifically knowledgeable of 19 psychiatry, do you have opinions as to whether or not Prozac 20 caused Joseph Wesbecker to do what he did on September 14th, 21 1989? 22 MR. FREEMAN: Objection, Your Honor. 23 JUDGE POTTER: Let me see you-all again. 24 (BENCH DISCUSSION) 25 MR. FREEMAN: We'd like to be heard in chambers 43 1 and take a break, please. 2 JUDGE POTTER: We'll just take the morning 3 recess a little early. 4 MR. SMITH: I can go on to something else. You 5 know, I can -- 6 JUDGE POTTER: Well, what is it? Let me just 7 get that straight. Because I'd hate to go back and find out 8 it's just a rephrasing of the question. Are we getting to the 9 motion in limine? 10 MR. FREEMAN: The motion in limine and the 11 relevancy and the basis for his opinions, he's clearly in the 12 minority view on all of these issues. 13 JUDGE POTTER: Mr. Smith, knowing that's going 14 to be the objection, is there any other evidence you want to 15 put in before the jury before we take a recess and talk about 16 that? 17 MR. SMITH: I could put in some more stuff. 18 JUDGE POTTER: It's up to you. 19 MR. SMITH: How are you going to rule, Judge. I 20 mean -- 21 JUDGE POTTER: Okay. It's just up to you. Do 22 you want to take the break now? 23 MR. SMITH: That's fine. 24 (BENCH DISCUSSION CONCLUDED) 25 JUDGE POTTER: Ladies and gentlemen, we're going 44 1 to take our morning recess a little early this morning. As 2 I've mentioned to you-all, do not permit anyone to speak to or 3 communicate with you in connection with this trial. Do not 4 discuss it among yourselves and do not form or express any 5 opinions about it, and we're going to take a half an hour. 6 The recess will be a half an hour. 7 (THE FOLLOWING PROCEEDINGS OCCURRED 8 OUTSIDE THE PRESENCE OF THE JURY) 9 JUDGE POTTER: Mr. Freeman, Mr. Stopher, why 10 don't you go ahead and make the motion that you want to make. 11 MR. FREEMAN: We'd like to excuse the witness 12 while we're making the motion. 13 JUDGE POTTER: Wait just a second. It's my 14 understanding, then, that you do not want to elicit any 15 testimony from the witness to support your motion; is that 16 right? 17 MR. FREEMAN: No, sir. We'll rely on the record 18 as it stands. 19 JUDGE POTTER: The record as it stands is his 20 testimony in the courtroom today. Doctor, could I ask you 21 just to wait out front? 22 DOCTOR BREGGIN: Yes, sir. 23 JUDGE POTTER: Okay. Thank you. 24 (DOCTOR BREGGIN LEAVES THE COURTROOM) 25 JUDGE POTTER: Mr. Smith, is there anything you 45 1 want to say before they make their motion? 2 MR. SMITH: Number One, I thought that the 3 Defendants had represented that they were not going to make 4 the motion in order to avoid us reading any deposition 5 testimony, that that was going to be something that was going 6 to be done at a later date. 7 JUDGE POTTER: Okay. What do you say to that, 8 Mr. Freeman? And I did -- I was kind of under the impression 9 that as part of him not reading depositions and putting in his 10 case through cross-examination of some of the live witnesses 11 you were going to get down here, I know there was definitely 12 agreement about the motion for directed verdict. What is your 13 feeling about a motion on Doctor Breggin? 14 MR. FREEMAN: The motion on Doctor Breggin is 15 directed to a number of issues that have nothing whatever to 16 do with him reading additional depositions or otherwise. 17 JUDGE POTTER: Okay. Well, let's see what your 18 motion is and then I'll let Mr. Smith decide whether or not he 19 thinks... 20 MR. FREEMAN: Your Honor, first of all, we'd 21 like to move to prevent this Witness from giving any opinion 22 in this case upon the following grounds, including among the 23 following grounds are the fact that the evidence as it now 24 stands in the case would not support him being able to give 25 any opinion. Now, specifically what I'm talking about is that 46 1 the Witness has talked about medical records. He's talked 2 about FDA documents. He's talked about depositions, he's 3 talked about a number of things. I'm not talking about Lilly 4 employee depositions, but I'm talking about a number of things 5 that he now wishes to summarize and give conclusions about, 6 not with respect to how serotonin specifically works, but to 7 arrive at an opinion on what caused Joe Wesbecker to do what 8 he did on the day in question. Now, to summarize or synopsize 9 matters that are nowhere in the evidence -- for example, the 10 medical records: For example, the FDA information that he 11 claims to have gotten from the FDA by way of microfiche; for 12 example, the documents that he claims he's basing an opinion 13 on as respects the documents that were obtained from Lilly. 14 And to summarize those and to come up with some opinion that 15 these in some way caused this man to do what he did is clearly 16 not permissible. 17 The second part of his testimony is 18 scientifically and under the Daubert decision, in direct 19 conflict with each other. For example, in the first part of 20 his deposition or his testimony, he started talking about what 21 happens when the system gets sluggish, what happens when the 22 neurotransmitter serotonin is sluggish and is not acting in 23 the appropriate way, and then he goes to an analysis of the 24 desensitizing the receptors and what happens then, and then he 25 says in summary all of these things are purely hypothetical, 47 1 they are guesses, and tomorrow the whole premise of what I'm 2 saying may not even be believed by anyone, because we have 3 analyses that have occurred back in the early days as to what 4 happens to cause depression and now we know none of these 5 things in fact ever happened. 6 He also then starts into a debate about what 7 occurs when one takes Prozac, and then he says while some of 8 these things are known by Lilly and based upon Lilly's 9 studies, he doesn't introduce anything to show any Lilly study 10 or any study from anybody whomsoever that support anything. In 11 other words, he's arriving at a conclusion with respect to 12 what happens to the postsynaptic receptors, what happens to 13 the presynaptic production of serotonin. That is all, in his 14 opinion, guess or speculation. 15 There has been no foundation laid in this 16 connection with respect to any of these premises other than a 17 blanket statement made by him without any direct evidence to 18 support the evidence that these matters that he now says are 19 hypothetical are generally accepted by anyone whomsoever. 20 Now, we need to have some basis in the evidence for him to 21 arrive at these opinions that he has earlier stated and we 22 suggest to the Court that by his own testimony they are 23 hypothetical in nature, they are speculative in nature and 24 they do not support him being allowed to give any opinion at 25 this time. I'd like just a brief minute to confer with my two 48 1 counsel. 2 As I did earlier when we came to the bench, Your 3 Honor, both this time and on yesterday, we incorporate in our 4 objections to his testimony all of the matters that we set 5 forth in the motion in limine, which we've done at the bench 6 twice, and now reincorporate in this matter that we're taking 7 up before the Court on causation. 8 JUDGE POTTER: Mr. Smith. 9 MR. SMITH: I think that we've established that 10 the Witness is qualified by virtue of his training and 11 experience and his review of the scientific literature to 12 express opinions in connection with Prozac and in connection 13 with psychiatric medications and in connection with conduct of 14 human beings under the influence of psychiatric medications. 15 I think Doctor Breggin was clear in enunciating what his 16 theory, what is proven, what is unproven and what the 17 scientific literature is in connection with that. 18 I think that what Doctor Breggin has testified 19 to in 89 to 90 percent is uncontroverted from his own 20 testimony concerning serotonin. The problem with Lilly is 21 they don't agree with some of the conclusions reached by 22 Doctor Breggin. That, of course, is specifically addressed by 23 Daubert, which is the controlling case in this situation. And 24 Daubert says if there is a scientific basis for your 25 conclusions, if there is reasonable basis in science to draw 49 1 such a conclusion, it's permissible to make the opinion, 2 regardless of whether or not it's generally accepted within 3 the scientific community. 4 Now, I am prepared to and intend to with this 5 Witness take him through the animal studies, the normal human 6 studies, the clinical trials and the postmarketing experience 7 with this drug to establish scientifically that this drug does 8 produce this particular side-effect profile. I think Doctor 9 Breggin testified to it generally, but he can testify as to it 10 specifically. I intend to and am prepared to take Doctor 11 Breggin through and Doctor Breggin is going to make an 12 analysis of Mr. Wesbecker's psychiatric background and discuss 13 the stressors involved in Mr. Wesbecker and the effects of 14 Prozac scientifically on Mr. Wesbecker generally and 15 specifically. The only problem that Lilly has is that they 16 don't agree with his conclusions. 17 Now, I can back this up and go through that 18 entire analysis. I intend to do it anyway, Your Honor, but I 19 was of the -- under the impression that by virtue of the Court 20 desiring that there be in-person testimony from Lilly 21 witnesses and by virtue of the Court's desire to reduce trial 22 time and to save the jury the boring exercise of us reading a 23 lot of depositions, scientific literature into evidence and 24 depositions into evidence, that this motion would be deferred 25 until the conclusion of not only the plaintiffs' case but the 50 1 defendant's case. 2 JUDGE POTTER: Well, Mr. Freeman, is there 3 anything you want to say before I rule on this point? 4 MR. FREEMAN: Yes. I think the briefs clearly 5 speak to what was held to be in Daubert, and one thing that 6 I'd like to point out in particularly that we're talking about 7 now causation as opposed to anything else. We're talking now 8 about the ability of this man to take this complex situation 9 and scientifically testify that it was caused by Prozac and to 10 be able to support it in the scientific literature as far as 11 predictability, as far as duplicating it and all of the 12 elements that we set forth on Page 17 through 19 of our brief 13 in limine. 14 JUDGE POTTER: In deciding whether or not to let 15 a person testify as to an expert, there are several hoops that 16 a person opposing that witness has to jump through, one, that 17 the witness is qualified as an expert by knowledge, et cetera, 18 and I think that's been done with this gentleman. And the 19 second thing is what can he be allowed to use or rely on in 20 forming his opinion. The Kentucky Rules of Evidence are 21 really very forgiving in that and the fact that he's relying 22 on some things, the depositions, the medical records, a lot of 23 things like that that are not in evidence yet, I don't think 24 prevents him from expressing an opinion on those topics. Mr. 25 Smith did not ask him a magic question you often hear, "Well, 51 1 Doctor, are these the kind of things that a person in your 2 position normally relies on, et cetera, et cetera," whatever 3 it takes to fill in Rule 703P, but I think it's plain that the 4 medical records, the documents, maybe when he's getting down 5 to a conversation with Doctor Kapit, maybe he's getting on the 6 edge there, but I do think that the things upon which he 7 purports to rely are permissible. The -- and I think we get 8 to what you-all call the Daubert problem or whatever it is is 9 whether his opinions rise to the level of scientific knowledge 10 under 702. I think that Kentucky has adopted a rule similar 11 to the federal rule, and that to the extent Kentucky would 12 previously put a harsher test, formerly called I think the 13 Frye test, they would retreat from that and follow the supreme 14 court case of Daubert. 15 People tend to forget Daubert was a plaintiff's 16 case. It was a case where the lower courts, if I remember 17 correctly, had not allowed certain testimony because it wasn't 18 scientifically acceptable enough and the Supreme Court said, 19 "Yes, we're going to permit it." I think in judging Mr. 20 Breggin you have to look at what the other testimony has been 21 and what everybody agrees it is going to be, and when I said 22 going to be I was talking about if it's accepted in a light 23 most favorable to the plaintiffs. As I understand it, they 24 anticipate putting on some testimony, and perhaps already 25 have, that if accepted would say that these statistical 52 1 studies and the behavioral clinical trials and whatnot 2 properly analyzed would indicate that Prozac could cause in 3 people suicide or aggression. I see this gentleman as more or 4 less providing a theoretical framework in which the brain or 5 the chemical could act within a person to produce these 6 results. So even though he can't be very sure about and admit 7 that, you know, some of what he's saying is a hypothesis, it 8 is an explanation for how these things could happen, which Mr. 9 Smith I think intends to show by statistical studies analyzed 10 his way in fact do happen. So I don't think his testimony 11 perhaps has to rise to the level of scientific certainty he 12 would have to have if he were the only witness testifying. 13 So I find that his opinion is scientific 14 knowledge that would assist the trier of fact in understanding 15 this evidence. I think it will be helpful to the jury to have 16 one say -- somebody say yes, we accept Mr. Smith's testimony, 17 the clinical trials show thus. This gentleman's testimony 18 shows a method by which, it may be hypothetical, but as I 19 understand it, it's maybe not more hypothetical than some of 20 the stuff that everybody's accepting in connection with this 21 drug now, his testimony shows how it could have happened. 22 So on the evidence that I've heard so far, I'm 23 going to deny the motion to prevent Doctor Breggin from 24 answering the question: Does he have an opinion as to what 25 caused Mr. Wesbecker, and then go into an explanation of how 53 1 the mechanics of his -- the mechanics of Prozac would operate 2 on a brain to produce that result. So the motion is denied. 3 MR. FREEMAN: While we are out, may I take up 4 one additional matter, please? 5 JUDGE POTTER: Uh-huh. 6 MR. FREEMAN: As you know, we approached the 7 bench earlier about the coroner's inquest. Mr. Smith conceded 8 graciously, as always, to your rulings and instructed the 9 Witness not to go any further. 10 JUDGE POTTER: Just chat with him over the 11 break. 12 MR. FREEMAN: The only other thing I wanted to 13 take up was the proposition that this Witness should not be 14 allowed to go into the content of one-way conversation with 15 any person whomsoever or otherwise. He can testify what he 16 did in response to some of these things, but he can't go in 17 and synopsize certainly what Kapit or any of the other people 18 he talked to at the FDA had to do with this particular 19 conversation. 20 JUDGE POTTER: What's the fellow's name at FDA? 21 MS. ZETTLER: K-A-P-I-T. 22 JUDGE POTTER: K-A-P-I-T. Okay. I take it 23 Doctor Kapit, is he going to be part of what we'll hear the 24 rest of today or not? 25 MR. SMITH: Not a large part. Doctor Breggin 54 1 talked with him on a couple of occasions concerning the 2 warning labels that were proposed and discussions that were 3 had with the FDA. Certainly Lilly's been talking with the FDA 4 since 1978 about this drug. Are they saying that we can't 5 talk -- our expert can't testify concerning what the FDA said 6 to them. You know, the problem is, Lilly gets to talk to 7 them, but we can't even take their depositions. 8 JUDGE POTTER: Well -- 9 MR. SMITH: Doctor Thompson testified many times 10 the FDA says we're the best; the FDA says this; the FDA says 11 this. It's certainly not going to be the cornerstone. 12 JUDGE POTTER: I can see where certain things 13 that he heard from -- if he identifies Mr. Kapit correctly and 14 talks about his position, I should think he would be able to 15 rely on some information that Mr. Kapit gave him. I can think 16 of an awful lot of information that Mr. Kapit might have given 17 him that he couldn't rely on, so I really don't know what to 18 do other than say, Mr. Freeman, you just need to be quick on 19 your feet and if he starts to talk about Mr. Kapit in some way 20 that you think is inappropriate, make an objection and I'll 21 rule on it. 22 But, Mr. Smith, I do think if it gets down to 23 "Mr. Kapit told me his opinion was thus and so," or "Mr. Kapit 24 felt it was a stimulant," or what did he call it? 25 MR. FREEMAN: Yes, sir. A stimulant. 55 55 1 JUDGE POTTER: I think maybe he's probably 2 crossed over there. Before he gets there I don't know when he 3 crosses the line but, I mean, this is his opinion, he needs to 4 base it on stuff he's read and stuff in this record and 5 whatnot, and not what Mr. Kapit told him about what he thinks 6 it is. 7 MR. SMITH: Those conversations certainly aren't 8 the cornerstone of our case, Your Honor. 9 JUDGE POTTER: I didn't think they were, but if 10 they're even a little piece, why don't you see if we can get 11 him to leave it out of his opinion. Why don't we take ten 12 more minutes and then we'll come back. 13 (RECESS) 14 JUDGE POTTER: Doctor Breggin, I remind you 15 you're still under oath. 16 Mr. Smith. 17 Q. Doctor Breggin, I'll repeat my last question. 18 Based on the thousands of pages of material that you reviewed, 19 the hundreds of hours that you've spent in reviewing this 20 case, based on your training and experience, do you have an 21 opinion as to the cause of Joseph Wesbecker's conduct on 22 September 14th, 1989? 23 A. I do. 24 Q. What is that opinion, sir? 25 A. That Prozac was a substantial factor, a cause, 56 1 in the events of that date in the production of violence, in 2 the production of suicide, and that it would not have happened 3 without Prozac. 4 Q. All right. Let's back up, then, Doctor Breggin, 5 and carefully tell us the basis in detail for that opinion 6 that you're giving here. Prozac is a drug; Joseph Wesbecker 7 was a human being. How did you start to come to the opinion 8 that this drug caused this human being to conduct himself in 9 such an unusual, tragic way? 10 A. Before I became aware of this case, I had 11 already realized that the drug has a stimulant profile, that 12 it produces agitation, that it can produce this manic kind of 13 behavior in the extreme and paranoid behavior. I was hearing 14 in the workshops that I gave around the country story after 15 story of patients becoming violent, becoming suicidal -- 16 MR. FREEMAN: Objection, Judge. 17 JUDGE POTTER: Objection is overruled. 18 A. -- of patients becoming violent, becoming 19 suicidal in a very compulsive, unusually unexpected violent 20 manner, and I began to have the opportunity to see some of the 21 case material to interview some of the people and then again 22 to look more intensely into the question, first, is this a 23 stimulant drug, and can it produce these behaviors. 24 And what I'd like to do in some detail, because 25 this is such an important question, in some detail to take you 57 1 through some of the materials I've looked at confirming these 2 opinions. And I want to apologize for using memory prompters 3 because there's just so much, and I'm going to try to make it 4 pithy, but I want to get the material to you. I'd like to 5 start with animal studies. 6 Q. All right. These animals studies, who conducted 7 these animal studies, Doctor Breggin? 8 A. The studies that I'm going to describe were 9 conducted by Lilly I believe almost entirely. I'll check as I 10 go through. 11 Q. All right. Tell the jury about the animal 12 studies that you have reviewed. 13 A. Well, first of all, it's important to test a 14 drug on an animal and on a variety of animals because it gives 15 us a sense, a direction of its effect on people, at least it 16 may. Now, human beings are so much more complex, not only in 17 their brain but in their human experience that gets encoded 18 into the person. We're so much more complex that you just 19 can't go from animal to human on an issue like this, but you 20 can get a direction. Because animals are so much more rigid 21 and limited than human beings, you might get to see the 22 direction better in higher doses than are given to human 23 beings because you get to see the extreme effect on the 24 animal, and it may give you a warning, a signal about human 25 beings. And there were many signals that this drug had a 58 1 particular behavioral effect. 2 Lilly did not study the drug for behavior in 3 large animals. We don't have, as far as I know, at least, any 4 studies by Eli Lilly specifically to look at -- during the 5 drug approval period to look at what a monkey -- how a monkey 6 would respond, for example. What we have instead is to make 7 inferences when they were trying to study something other than 8 behavior. They didn't specifically look at the behaviors of 9 large animals but only of rats and mice, which makes it very 10 hard to extrapolate. 11 Q. Would these have been the same things as the 12 toxicology studies that have been described earlier, Doctor 13 Breggin? 14 A. Well, some are toxicology. Let me start with 15 1978. In 1978, from the Lilly Research Labs, Doctors Slater, 16 Jones and Moore published an article, and I'll read you the 17 paragraph that they wrote describing their findings, their 18 summary paragraph. During the course of these experiments -- 19 these were on cats -- "During the course of these experiments, 20 two unexpected findings were encountered. The present authors 21 are at a loss to explain why cats receiving fluoxetine for 22 several days began to hiss and growl and why this behavior 23 decreased with continued treatment." They go on to say -- 24 this is continuous -- "The subjects who received fluoxetine in 25 Phase 1 clinical trial..." -- that's the very earliest trial. 59 1 Phase 1 is where you're not doing anything very scientific; 2 you're just seeing, to start with, is this drug safe in 3 people. They say people in the Phase 1 clinical trial, and 4 they refer to an unpublished paper so we can't check, have not 5 described any change in blood nor have observed, noted any 6 change in affect. In other words, what they're saying, we 7 have this finding in cats, we don't understand it because 8 people aren't responding this way. We shall find, in fact, 9 people were responding this way in the earliest Lilly trials 10 right -- in the development of the animal research. 11 Another source of information is a report from a 12 man named Brophy, who was a project leader at Lilly, and he's 13 talking now about dogs getting very high doses of the drug. 14 "A total of six dogs, two males and four females from the 15 high-dose group were removed from treatment for periods of 16 1 to 17 days due to severe occurrences of either aggressive 17 behavior, ataxia or anorexia." Now, this is important because 18 anorexia is a part of a stimulant syndrome and aggressivity is 19 a part of a stimulant syndrome. Ataxia simply means imbalance 20 from being toxic on the drug. That could have happened 21 probably on large doses of many different drugs. 22 In addition, according to this report, one of 23 the dogs in the toxic study who died of -- purposely, you 24 know, they were testing the toxic dose. One of the dogs 25 showed, quote, marked aggressive behavior. Technician bit 60 1 attempting dosing. There was also tremor that was anorexia in 2 these animals. This is very early on. This particular memo 3 is from 1981. 4 Q. Doctor, couldn't that behavior in the cats and 5 the dogs -- it said in the article itself that these animals 6 were on large doses. Couldn't the aggression there be 7 attributed simply to the fact that this was large doses? 8 A. Well, no. This is a very specific effect. The 9 doses in the cat findings were not toxic, only the dog study 10 is a toxic level, as far as I recall. I'd have to check the 11 details, but, no. Because if you were giving a drug, for 12 example, that had sedative effects or tranquilizing effects in 13 large doses the dogs would be flaked out, the cats would be 14 flaked out, they would be docile. This is true for a whole 15 variety of medications. But instead, these dogs are getting 16 hyper, the animals as a group are getting hyper and 17 aggressive. So you're seeing another trend, you're getting a 18 signal this looks like a stimulant with the specific dangers 19 associated with amphetamines or PCP or other stimulants. 20 Violent behavior. 21 This study is confirmed in a depo by Doctor 22 Fuller, the highest ranking scientist, who said that 6 of 20 23 dogs in the high-dose study group became aggressive, to his 24 knowledge. It's Page 368 of his deposition. 25 Q. Is that statistically significant, 6 out of 20 61 1 dogs becoming stimulated? 2 A. Well, it certainly looks at -- I'm not a 3 statistician, but it certainly looks like a very significant 4 figure, and I think they thought it was significant. It's a 5 signal. It's a trend. The trend continues in every class of 6 animal. 7 Q. Continue, Doctor Breggin. 8 A. Even earlier with smaller animals in 1974, rats 9 given nonlethal doses developed pronounced hyperirritability. 10 I've worked with rats. That probably means, you know, people 11 start to get wary of these rats, irritable, and some of it 12 disappeared from the rats. 13 Then mice. Now, this is from a report in 1986, 14 but I believe it's on an earlier study, and the report is part 15 of the material Lilly had submitted to FDA, and it says of the 16 mice: "The significant effects were essentially limited to 17 the high-dose group and consisted of mortality, 15 percent, 18 persistent hyperactivity, decreased body weight, and then a 19 variety of other mobile chemical and not-relevant-to-us 20 findings. 21 So, again, we have these two findings, either 22 aggressivity or hyperactivity, and body weight loss, the very 23 amphetamine-like response. And in another source, a 24 pharmacological review that was a part of the approval 25 process, it said that hyperactivity is seen in 11 mice in 62 1 toxic studies and this particular group of mice died. 2 So we have here in the earliest studies, 3 signals; as far as I know, none of these studies were followed 4 up. I don't know. I didn't find anywhere in these volumes of 5 pages anybody saying let's do this again, let's try it on 6 chimpanzees, let's see what's going on here. We're getting 7 hyperactivity, we're getting irritability, we're getting 8 aggression, we're even getting bit on at least one occasion. 9 The early human studies also give these flags, contrary to 10 what Doctor Slater published. 11 Q. Now, if you see, in your opinion, Doctor 12 Breggin, this type of behavior in your early animal studies, 13 should that be taken into account in any way in designing or 14 analyzing the clinical trials to where you're going to be 15 giving the drugs to humans? 16 A. Yes. 17 Q. All right. Can you explain that, why and how? 18 A. Well, your signal is that we're getting 19 hyperactivity, aggressivity and weight loss. We may have a 20 classic stimulant. With the dangers of a classic stimulant, 21 let's design very early studies. First of all, let's not give 22 it to people, let's start with some animal studies that are 23 more sophisticated than that. The other thing is to begin to 24 think of the early human studies in terms of setting up really 25 an in-depth examination in terms of whether people are getting 63 1 more irritable, getting more agitated, how they respond to 2 you. They're not likely to get, on the average, grossly 3 violent. That may only happen 1 in 100 times, but that's a 4 catastrophe; 1 in 1,000 is a catastrophe; just once is a 5 catastrophe. So you want to look at whether this is a 6 possibility with special tests, with in-depth evaluations. 7 Q. Go ahead, Doctor Breggin. 8 A. The material we have on the very earliest 9 studies from Lilly comes again from their own researchers, 10 from their memos. And here we go back to July 1979, a memo by 11 the chief scientist at Lilly, Ray Fuller, and he's talking 12 about an open-label study. An open-label study is where 13 everybody knows who's getting the drug, you're just beginning. 14 It's not like you're doing a real controlled study and you 15 don't know who is getting what, but giving some patients 16 fluoxetine and seeing what happens. 17 And here's what Doctor Fuller wrote and 18 confirmed in his deposition: "Some patients have converted 19 from severe depression to agitation within a few days." Some 20 patients. Right away, flagging just like the animal studies. 21 I'll continue with the quote uninterrupted. "In one case the 22 agitation was marked and the patient had to be taken off drug. 23 In future studies, the use of benzodiazepines to control 24 agitation would be or was -- I can't quite read that -- will 25 be permitted." 64 1 So very early on they have a catastrophe, 2 serious agitation, they get worried and they start to think 3 we'll combine the drug with a sedative right away. Now, this 4 has enormous implications. I'm not sure if this is the point 5 to get into it, but it has enormous implications. 6 I mean, sedatives are addictive. If the drug is 7 going to be approved is it going to be approved as a drug plus 8 a sedative; that's what they're suggesting. A drug plus a 9 sedative is addictive. You've got a whole other series of 10 problems involved here if from the beginning you're saying 11 this drug is in effect so stimulating as to cause agitation. 12 And, remember, agitation includes irritability. It's the 13 beginning of aggressivity. Then, I mean, there's something 14 very special going on early. 15 Another early memo found in August '79, that one 16 doctor who tried Prozac on just two patients that were still 17 doing this open study, we'll try it, we'll see what happens. 18 He tries it on two patients, one person gets very suicidal and 19 gets a thought disorder, begins to look schizophrenic and has 20 to be put on a neuroleptic antipsychotic medication, and they 21 conclude, well, maybe this person was already schizoaffective, 22 the same diagnosis -- schizophrenic, same diagnosis, 23 schizoaffective as Mr. Wesbecker. So they're getting another 24 signal here that maybe something happens to people with this 25 drug. And the other person they said was just a simple 65 1 failure. 2 Q. Doctor Breggin, is that taken from Doctor 3 Slater's notes and memos and depositions in connection with 4 his experience with Doctor Gosenfeld, I believe, in California 5 somewhere? We have that in evidence. 6 A. I don't know, sir. I don't recall what the 7 source was of this, other than it's a direct quote on 8 August 21st, 1979. So perhaps you could make that connection, 9 but I can't. 10 Q. I think we have that in evidence, Doctor 11 Breggin. 12 MR. FREEMAN: Object to the comment, Your Honor. 13 14 JUDGE POTTER: Okay. Overruled. 15 A. The -- I explained to you earlier who Richard 16 Kapit is, a psychiatrist, a doctor, a published author, and 17 the chief medical officer at the FDA for the specific purpose 18 of writing the safety reviews of Prozac. And I want to take 19 you through his safety reviews. 20 And we start with a very early Phase 2 report. 21 We're out of the Phase 1, now we're into Phase 2, and in Phase 22 2 you begin to do a somewhat larger number of patients. You 23 may do some controlled studies; you may not. You've kind of 24 moved from "Here's a drug, how did you do" to "Let's look a 25 little more carefully, a little more systematically to see if 66 1 we should proceed to the very expensive and more risky 2 increase in numbers to the final approval process. And what 3 Kapit wrote in March '86 was that there were five, quote, 4 serious clinical events in the first 77 patients. Now, first 5 of all, note that he does not report among these first 77 6 patients the stuff that we read about. It doesn't somehow 7 make it into that list of 77 patients given to the FDA. 8 Q. Did you check that to confirm that, Doctor 9 Breggin? 10 A. Well, yes; he's very specific. He says that 11 there was a -- out of the 77 patients there were a number of 12 problems and there were two particular ones, a paranoid 13 psychosis and a manic psychosis, and this is very relevant to 14 the Wesbecker issues because Mr. Wesbecker very well may have 15 had a drug-induced paranoid psychosis, a delusion about things 16 being done to him at his workplace that enrages him and makes 17 him want to take an action. That would be a classic paranoid 18 psychosis in this case, and in the cases here very likely drug 19 induced. Now, out of these 77 patients we have two people 20 with such severe reactions, again, a serious signal. One 21 could raise the issue that it just happened to happen with 22 these upset people and this happened to happen, well, this is 23 certainly a very strong warning signal. 24 Meanwhile, the issue of patients getting 25 agitated was getting more and more documented. Doctor Slater 67 1 authorized the use of diazepam specifically to reduce 2 agitation in patients in the early studies. That's on Page 3 364 of his deposition, and he admits that the drug could cause 4 agitation and that tranquilizers were given for it, and that 5 others, that not himself, were mentioning excessive 6 stimulation and agitation from this drug, and that's on Page 7 379. And he's not sure if that's been reported. He said -- I 8 think he was implying to the FDA. 9 Now, by the time they began to do the protocols 10 for Phase 3, let me explain that to you. We now go into the 11 third phase of FDA testing and this is where they try to do 12 the more elegant scientific studies. These studies have vast 13 limitations that we can talk about later, but they're an 14 attempt to make it scientific. And how do you make it 15 scientific? You make it scientific by not letting the 16 patients or the doctors or the raters or anyone know who is 17 getting what drug. So, in fact, all the pills look alike. 18 You may give a placebo or sugar pill that has no effect, 19 Prozac, you may give another class of antidepressant and 20 compare them and they all look alike and they're given in the 21 same schedule, so you can't tell supposedly who's getting 22 what. Now in fact doctors can usually tell. We'll go into 23 that later, but they can often tell, at least, because the 24 drugs have such different effects, they know if a patient is 25 getting sleepy or agitated from the drug. 68 1 But the important thing is these are the studies 2 that are going to be the more scientifically based used for 3 approval and from the start in two protocols, one of which 4 became a key protocol approval, Protocol 19. It was written 5 in that if the patient got agitated you could give them a 6 sedative drug, one of these literally quite-addictive sedative 7 drugs. Protocol 19 and 22 specifically says -- and this is a 8 specific protocol that was written by Lilly. The FDA or the 9 investigators out in the field don't write the protocol; this 10 is Lilly writing the protocol. Quote, if a patient complains 11 of agitation the dose of study drug should be reduced and the 12 patient may receive a benzodiazepine at the investigator's 13 discretion. 14 Q. What's wrong with that, Doctor Breggin? These 15 people might have been agitated or anxious to start with or 16 they might have even had treatment, emergent anxiety or 17 agitation. What's wrong with helping these people with some 18 type of sedative or sleeping pill? 19 A. Well, there's two things about it, one, just 20 simply the information it gives us. The information it gives 21 us is that they expected the drug was doing it. The drug 22 should be reduced, so they're clearly saying to the clinical 23 investigators if you see agitation cut back on the drug. They 24 never put it in the label. The average psychiatrist didn't 25 know this when it came out that the study was based on looking 69 1 for agitation, cutting back on the drug because it was the 2 cause and then adding a sedative. So that's one of the things 3 the information gives us, but it did not get out to the 4 medical profession at all and had to be learned over time. As 5 one of Lilly's experts said, "We learned over time that you 6 had to be careful about the drug dose, you had to add 7 sedatives." 8 The use, by the way, here of sedation, they 9 don't mean a sleeping pill at night. They don't mean like the 10 Restoril that Mr. Wesbecker got at night, which is a sleeping 11 pill. That's called a hypnotic. That's a short-acting, it 12 gives you a good night's sleep, doesn't affect you in the 13 morning very much and not at all during the day, hopefully. 14 They're talking about a regular regimen of giving drugs, 15 medications during the day to control -- that's what's meant 16 to control anxiety. It's not a sleeping pill, it's very 17 different than the treatment of Mr. Wesbecker. But there are 18 so many other problems with doing this. Basically what 19 they're saying is we are testing a combination drug without 20 telling the public that what got approved wasn't Prozac but 21 Prozac often in combination with the addictive sedatives to 22 control agitation. This was very important. 23 Now, in one of the studies that was used for -- 24 now, as I said, 19 was one of the protocols used for approval; 25 27, they were only allowed to give sleeping pills and yet they 70 1 ended up giving a big percentage of patients daytime 2 tranquilization anyway. We don't know exactly the percentage, 3 it's not fully clear, but the data was not produced. 4 Q. Are you saying, Doctor Breggin, that even though 5 the protocol only allowed sleeping pills, that in fact what 6 occurred was that investigators did indeed administer 7 sedatives during the day for agitation and anxiety? 8 A. Yes. They not only did that, but when Lilly 9 examined later their data they couldn't prove the drug helped 10 people if they took out the patients who had the sedatives. 11 The only way the drug looked good and was statistically 12 effective was when they kept the patients on the tranquilizing 13 or sedating drugs. 14 Q. All right. Continue. 15 A. Now, none of this was lost on Richard Kapit, 16 the -- again, the man doing the main analysis at the FDA. He 17 said from very early on in 1985, when he addressed the PDAC, 18 the committee that approves Prozac or doesn't approve it, he 19 said that the drug's most common side effects or effects, but 20 he said side effects were, quote, anxiety, nervousness, 21 insomnia, dizziness and nausea. With the exception of 22 dizziness, that's your typical amphetamine profile. And he 23 said on Page 255 of the transcript that, quote, fluoxetine is 24 more of a stimulant. He pointed out that the two most 25 dangerous effects of fluoxetine were dermatological reactions, 71 1 skin reactions, and psychosis. And he said the side-effect 2 profile of fluoxetine, which appears to be more that of a 3 stimulant drug compared to other antidepressants, 15 percent 4 of patients were getting anxious, 17 percent were getting 5 insomnia, 21 percent were getting nervousness. And this is 6 happening in very limited controlled studies. 7 Q. Even with the use of benzodiazepines, sedatives? 8 A. That's right. 9 Q. Even where the rules were designed to reduce the 10 risks? 11 A. Yeah. 12 Q. Is that right, Doctor? 13 A. Yeah. Even where the rules were designed, as 14 you put it, to reduce the risk they're getting these kind of 15 rates and, furthermore, they don't have patients included in 16 this group like Mr. Wesbecker who was known to have been 17 agitated, severely agitated earlier, who had earlier been 18 given diagnoses like manic depressive, and manic means with a 19 huge tendency to get agitated. Those people were all excluded 20 from the Lilly studies. So we're getting these effects even 21 in a group that is getting help from sedatives, estimates 22 being about a third of them, and in a group in which some of 23 the more likely responders with agitation are ruled out. 24 Now, Kapit went on to say that a lot of these 25 symptoms looked like some depressed patients. Remember when 72 1 Mr. Wesbecker gets depressed he sometimes gets agitated, that 2 when he first came to Doctor Coleman he had some agitation 3 just on the first severe, not as severe as when he took 4 Prozac. He had agitation at different times when he got 5 depressed. What Kapit said is be careful, it can make those 6 people more depressed, and he actually said it several 7 occasions. Here he's talking to the committee and he says 8 that he's afraid the drug can aggravate depression because, 9 quote, at least temporarily because of the increase in, quote, 10 nervousness, insomnia and disrupted appetite and weight loss; 11 that it can cause symptoms that are like depression and can 12 possibly worsen, and he repeats this a few times later on. I 13 know this is getting a bit repetitive, but I think it's 14 important to let you know that these themes that I have 15 described to you were repeated again and again. 16 In his final review for safety in March 1986, 17 Kapit again connected the stimulant effect to a possible 18 worsening of depression, and he said unlike standard tricyclic 19 antidepressants, unlike the common antidepressants to which 20 Prozac was being compared, fluoxetine's profile of adverse 21 effects more closely resembles that of a stimulant drug than 22 one that causes sedation and weight gain. Among treatment 23 emergent signs and symptoms, the most common effects produced 24 by fluoxetine include nausea, insomnia and nervousness. 25 Indeed, nervousness was the most common side effect reported 73 1 by long-term fluoxetine patients who discontinued therapy due 2 to an adverse reaction. He also pointed out it causes weight 3 loss and then he says -- and I want to read this carefully for 4 you. It's very important. It's something he said again and 5 again, and it was said in Germany by their agency like FDA, 6 and it's said in Britain by their agency what we're about to 7 hear coming from the FDA. "It is possible that these adverse 8 effects of fluoxetine treatment may negatively affect patients 9 with depression. Since depressed patients frequently suffer 10 from insomnia, nervousness, anorexia and weight loss, it is 11 possible that fluoxetine treatment might at least temporarily 12 make their illness worse." 13 Doctor Kapit repeats this under his summary in 14 detail so I won't put you through another repetition, and he 15 concludes suggested putting in the label that depression could 16 exacerbate -- be exacerbated. The symptoms of depression 17 could be exacerbated by Prozac. It did not get into the 18 label. 19 Now, after all the data was collected on 20 Prozac -- by 1986, pretty much all the data had been 21 collected. It wouldn't be approved till the end of January 22 of -- till the end of December of '87, wouldn't go into the 23 markets until '88, but by '86 they were just trying to 24 organize the data, figure out what was going on. And they 25 were worried that Prozac was producing a serotonin syndrome 74 1 that includes agitation, anxiety, upset stomach, headache, a 2 fairly elaborate syndrome. As a part of being concerned about 3 this, Kapit on December 17th, '86, tried to look some more at 4 the issues and he talked about a syndrome of 5 fluoxetine-induced hyperarousal or excessive stimulation. 6 That is just what I was drawing for you on the board where I 7 was saying that it's almost surely the excess production 8 because that's what the drug is aiming at doing. It's aiming 9 at excess production. It's aiming at enlivening or energizing 10 or activating this system, and he spoke of that syndrome of 11 fluoxetine-induced hyperarousal or excessive stimulation. And 12 he said, quote, they resemble episodes of stimulant drug 13 intoxication. In other words, this could look like an 14 amphetamine or a PCP psychosis or even LSD has that stimulant 15 kind of effect. 16 Q. Now, let's stop here and just let me interrupt 17 you for one second. You've used the term stimulant; you've 18 used the term amphetamine; you've used the term hyper. Is, 19 chemically, Prozac an amphetamine, like, say, Dexedrine or 20 amphetamine or something like that? 21 A. Well, it's interesting because the BGA, the 22 German FDA, got so concerned that they asked that question, 23 they came back to Lilly and said is this an amphetamine. 24 Q. You mean they actually -- 25 A. They asked it. Is this like an amphetamine. 75 1 Well, it's not in its chemical structure and the system it's 2 hitting most directly is only indirectly affected by the 3 amphetamines. The amphetamines particularly hit a system 4 called dopamine and stimulate it, but they also do stimulate 5 serotonin and we have that testified to by Lilly scientists 6 but less so, much less so. 7 Q. Well, is cocaine a serotonin reuptake inhibitor? 8 A. It, too, is. I mean, the stimulants have that 9 quality of inhibiting serotonin reuptake but it's really -- I 10 mean, it's important to understand that's not the main effect 11 that they're doing. I think we're getting the stimulation 12 syndrome here from two different chemical sources in the 13 brain. On the one hand, elevating norepinephrine and dopamine 14 can give you a lot of stimulation syndromes, but stimulating 15 Prozac we now know for sure and, in fact, it was showed up in 16 those early animal studies can do something very similar 17 clinically and behaviorally through a different system, but 18 there is overlap. Prozac affects dopamine somewhat and, 19 similarly, the amphetamines and cocaine affect serotonin 20 somewhat. But I don't think that's the key. 21 Q. What is the key then? 22 A. The key is that clinically we knew from early 23 on, and we'll see it repeated again and again, that 24 overarousing the serotonin system produced a stimulant 25 profile, indistinguishable virtually from amphetamines. Now, 76 1 I know in the letter in response to Germany, for example, Eli 2 Lilly argued that the weight loss rats got, their habits of 3 eating were not quite the same on amphetamines as serotoinin. 4 In one case, they ate less carbohydrate or in another case 5 less protein, but they couldn't deny this general effect, and 6 Kapit talks about it very specifically, fluoxetine-related 7 overstimulation. He warns about, quote, a syndrome of CNS, 8 that means brain, central nervous system hyperarousal or 9 overstimulation especially at high dose, but that it also 10 could occur at 20 milligrams and then he says it outright. 11 He's now talking about can Prozac cause addiction, and why is 12 he worried. He's worried because it looks like an amphetamine 13 and he refers to, quote, the -- I'm sorry, not looks like in 14 the sense of the molecule looks like but the effect looks 15 like. And he writes about, quote, the fact that fluoxetine 16 causes a set of adverse effects which resemble those caused by 17 amphetamine. This is the FDA's most knowledgeable, by far and 18 away. There's nobody that could hold a candle to Kapit in 19 terms of the vast amount of information on this that he 20 reviewed; everybody else is a boss, you know, the group leader 21 or the director. He's the doctor, the psychiatrist who's 22 reviewing all this, he says like an amphetamine. That's on 23 Page 23 of his November 17th, 1986 report. 24 And he concludes with a strong warning about a 25 syndrome of CNS hyperarousal or overstimulation, and he warns 77 1 that this can cause many different things, including 2 hyperactivity, hypomania, mania. And then makes a -- in this 3 process, by the way, he refers to one case of a bizarre 4 homicide on somebody taking Prozac, but then specifically says 5 that he doesn't see evidence to connect it causally, but he 6 does report this case in the context of Prozac. 7 Q. Why is it -- why is -- is there a connection 8 between a drug that has a stimulant profile and whether or not 9 that drug might induce an individual to commit a violent act? 10 A. All of the known heavy-duty stimulants, the 11 classic stimulants, the drugs that produce insomnia, 12 agitation, irritability, weight loss, that produce this, are 13 associated with paranoid psychoses in the extreme. That's 14 where you blame the whole world or some element of the world 15 for your problems and you take an action, maybe, you certainly 16 are fantasizing. Paranoid psychoses, they've been associated 17 with violence and also with suicide, and the suicide occurs 18 during the actual agitation, not necessarily during a crash 19 when you come off. You can crash when you come off of a 20 stimulant, but suicide's produced during the agitation. And 21 you can find this in the Diagnostic and Statistical Manual, 22 DSM-III, that was used during the period of time of Mr. 23 Wesbecker. And police -- I was just talking to a policeman 24 the other day and interviewed him on this, and he talked about 25 the superhuman strength -- 78 1 MR. FREEMAN: Your Honor, this has gone a little 2 far. 3 JUDGE POTTER: Sustained. 4 Q. Go ahead, Doctor Breggin. 5 A. I jumped a little ahead when I was talking about 6 the serotonin syndrome. He specifically addresses that whole 7 syndrome, they're trying to figure this out. During the month 8 that the drug is approved, they're still worried. This is 9 during the month that the approval is taking place. The 10 approval is in December, we're in November '87, the end of 11 November, and they're looking to see if there is a very 12 complicated stimulation phenomena that includes 13 hyperactivities, headache, dizziness, agitation, heart rate 14 sped up, blood pressure and a whole bunch of things, and they 15 conclude that there's a lot of suggestive evidence that for 16 some relatively smaller number of people get this whole thing, 17 but they conclude it's not sure. 18 But what's interesting for us is that we do 19 conclude about agitation, that is, one component. The 20 agitation component which they describe on Page 3 of this 21 document is -- this is their agitation component of the Prozac 22 reaction. The agitation component is anxiety, insomnia, 23 confusion, agitation, central nervous system stimulation and 24 irritability. 25 Now, Thomas Laughren, L-A-U-G-H-R-E-N, 79 1 physician, concluded from Kapit's materials that while the -- 2 the whole serotonin syndrome is in doubt, agitation was not. 3 And he said, in any case -- this is his boss, Kapit's boss -- 4 "In any case it seems clear from the material presented in 5 this amendment that fluoxetine is associated with several 6 findings from the categories identified as agitation and 7 movement disorder by the sponsor. In particular, anxiety and 8 insomnia from the agitation category and tremor from the 9 movement category seem to be quite common even at usual 10 therapeutic doses of Prozac." Quite common in therapeutic 11 doses. And it goes on to talk about how it gets even more 12 serious with larger doses. 13 And then in Kapit's evaluation he makes a most 14 startling observation and this has to do with the question of 15 what's causing it; is it the drug causing it or is it the 16 patient's illness that's causing it. And the way you try to 17 test that is by comparing placebo in the drug because, 18 remember, the patients getting placebo and getting the drug 19 were all supposed to be getting the same disorder. We've had 20 some which would skew results, but assuming that that's not 21 so, even, or assuming it is so, basically what you want to see 22 are people getting as agitated on the sugar pill as they are 23 on the drug. I hope that's clear. The question is are people 24 getting as agitated on the sugar pill and, indeed, well, in 25 this case, the sugar pill, the placebo, as they are on the 80 1 drug. And this is what they said. To consider an example -- 2 this is their quote: "To consider an example, 333 patients 3 who received fluoxetine experienced events in the agitation 4 group in contrast to 16 patients who received placebo." 5 Q. Did you say 60 or 16? 6 A. Sixteen. We have a ratio of 30 -- 333 to 16. I 7 don't have to be a statistician to tell you that is very, very 8 significant. The difference in sizes of these groups was 9 nowhere near enough to account for such a huge disproportion. 10 So it is the drug that's doing it. It's not -- now, the 11 patient's condition may contribute; that is, if you have a 12 more agitated patient you may get worse. 13 Q. But wouldn't you see also more agitated patients 14 on the sugar pill, Doctor? I mean -- 15 A. Yes. You'd see the same number. 16 Q. Theoretically, aren't you supposed to -- if you 17 have several components of the depression, won't you see this 18 not only in the Prozac group but in the placebo group? 19 A. Yes. 20 Q. And shouldn't the percentages be approximately 21 the same? 22 A. They should be approximately the same. Instead 23 of 16, you would expect at least 100 in the placebo group, 50, 24 100, I mean, depending on how large. But the placebo group 25 was a very significant fraction, like a third or so of the 81 1 Prozac group. 2 Q. So you're seeing 16 in placebo and how many on 3 Prozac? 4 A. Three hundred thirty-three. They thought it 5 mattered. I mean, the important thing is that Kapit thought 6 it was very important. While they continued to write about 7 this and they mention a paper by Steiner, this is again the 8 report by the FDA in which fluoxetine in combination with its 9 precursors. Well, tryptophan, in other words, the substance 10 you make serotonin from, when you gave people that along with 11 Prozac, you also got aggressive behavior. You can get 12 tryptophan in your diet. 13 Q. Is that all material that you've seen in looking 14 at FDA documents, all this stuff about Doctor Kapit? 15 A. Everything here is from Freedom of Information 16 that I got from the FDA, most of it that I got, some that I 17 believe you may have gotten. 18 Q. If the FDA is making these observations, Doctor 19 Breggin, I think the question on all of our minds is why 20 didn't the FDA take some action in this connection? 21 MR. FREEMAN: Objection, Your Honor. 22 Q. Based on your review of the material. 23 JUDGE POTTER: Mr. Smith, let me see you up here 24 for a second. 25 (BENCH DISCUSSION) 82 1 JUDGE POTTER: What's the answer going to be? 2 MR. SMITH: That it was hidden; that he thinks 3 that the upper management by virtue of their -- this influence 4 by Lilly didn't approve it. I'm not sure what he's going to 5 say, to be honest. 6 MR. FREEMAN: It's purely speculative, 7 conclusionary, irrelevant and immaterial and comes in contrast 8 of what the agency did. 9 MR. SMITH: Doctor Thompson was making a lot of 10 conclusion about what the FDA did or didn't do. 11 JUDGE POTTER: We're on this witness. If the 12 answer is going to be that because Lilly influenced them, I'm 13 going to sustain the objection. If it's because they ran 14 Protocol No. 22, and it came out perfect and therefore they 15 dropped it, you can ask him the question. I don't know how 16 you're going to handle it. 17 MR. SMITH: Okay. 18 (BENCH DISCUSSION CONCLUDED) 19 Q. Do you have an opinion, Doctor Breggin, whether 20 or not, regardless of what the FDA did or didn't do, this 21 material that is being developed concerning this particular 22 profile of this drug, whether or not Lilly could or should do 23 something back in 1986, '87, in the approval process of this 24 drug? 25 A. Yes, I do, sir. 83 1 Q. What is that opinion? 2 A. Well, they should have gone back. They should 3 have looked at the animal studies that I put together for you. 4 They should have looked at the findings they were getting. 5 They should have looked at some other data we're going to look 6 at on suicide in the trials and they should have said, "Stop 7 everything. We have more data than we've given you. We 8 notice you don't seem to have all the early data put together 9 on animals in one paragraph; it's scattered here and there. I 10 put it together for you. Even our earliest studies we had a 11 paranoid psychosis and a manic, but we have more than that, 12 you don't seem to realize. We've had all this agitation. 13 We've been using benzodiazepines to control it. Something's 14 off here." They should have held up approval themselves and 15 they should have given much more information to the FDA. The 16 next thing I was going to look at really by chance pertains to 17 that. 18 Q. All right. Give us some information, then, on 19 what was available from the clinical studies. 20 A. I want to get to that in a little bit when I get 21 to suicide because there was very definite data made available 22 that was not made available to the FDA, as far as I can tell. 23 But at one point, Doctor Beasley at Lilly decided himself to 24 review some of the studies that were going on to see what 25 percentage of patients were developing what he called an 84 1 activation syndrome, agitation, basically. And the syndrome 2 included anxiety, nervousness, insomnia, agitation, akathisia, 3 which is a hyperactivity that's drug induced -- I'll tell you 4 more about that later -- and central nervous system 5 stimulation. So he looked internally at this issue and he 6 found that 38 percent of the patients he looked at on Prozac 7 had this. He also concluded that 19 percent of the patients 8 on placebo had it, roughly half as many. Now, in fact, the 9 figures are even worse than this because when he counted the 10 numbers of patients who got this syndrome he didn't count 11 people who got manic, the extreme form, which wouldn't happen 12 in the placebo group hardly at all. Euphoria, tremor, 13 hyperactivity, nightmares. So even excluding a whole bunch of 14 the aspects of agitation, he found 38 percent of the patients 15 got agitated. Now, I have not been able to determine that 16 this material ever got to the FDA. 17 Q. Let me hand you, Doctor Breggin -- 18 A. It may have, incidentally, but I haven't been 19 able to determine that it has. 20 Q. -- what's been marked as Exhibit 70, and ask you 21 if that is the study by Doctor Beasley to which you're 22 referring? 23 A. Yes. It's called Activation and Sedation in 24 Fluoxetine Clinical Studies. 25 MR. SMITH: We would offer Exhibit 70, Your 85 1 Honor. 2 MR. FREEMAN: Same objection, Your Honor. 3 JUDGE POTTER: Be admitted. 4 DOCTOR BREGGIN: It is undated, which is why I 5 haven't given you a date, at least my copy is undated. This 6 appears to be undated. 7 MR. SMITH: I just have 13 of these, Your Honor. 8 Give me one of yours. Do we have any more copies somewhere? 9 MS. ZETTLER: Let me check. 10 MR. FREEMAN: Can we approach the bench, please? 11 (BENCH DISCUSSION) 12 MR. FREEMAN: This is that same document that's 13 never been identified by anybody whatsoever. It's not the 14 Beasley article which I thought it was to start with. It 15 doesn't have a name or date or anything on it. 16 MR. SMITH: It's authenticated as a PZ document. 17 JUDGE POTTER: Marsha, would you collect them 18 back up for the time being? 19 Okay. I misunderstood Mr. Freeman's objection. 20 We're down to the same thing, Mr. Smith. Unless this guy can 21 identify and you get it in, I'm going to sustain the 22 objection. I mean, we've been through this before and then we 23 thought about some procedure where there would be a deadline 24 to produce it and they'd either object. And it isn't a 25 question of -- this may even be a question of authenticity, 86 1 but no one can identify what this thing is. And you've said 2 it's by Doctor Beasley, but this guy doesn't know it's by 3 Doctor Beasley. 4 MR. FREEMAN: And I don't know it's by Doctor 5 Beasley. 6 MR. SMITH: It was reviewed by Doctor Breggin to 7 come to his conclusion. It was produced by Lilly from Lilly 8 files. We're offering it on the basis that it forms the basis 9 of an expert opinion. 10 JUDGE POTTER: But that does not permit you to 11 get it into evidence as an exhibit. 12 MR. SMITH: Okay. 13 JUDGE POTTER: Objection sustained. 14 (BENCH DISCUSSION CONCLUDED) 15 JUDGE POTTER: Madame Sheriff, would you give 16 the document back to Mr. Smith? I'm going to sustain the 17 objection. 18 Q. Briefly, Doctor Breggin, what were the 19 conclusions in that special study that was done by Lilly 20 concerning whether or not Prozac produced activation or 21 sedation in the clinical trials? 22 MR. FREEMAN: Your Honor, that's the same 23 objection if it's based upon that document. 24 JUDGE POTTER: Well, objection is overruled. He 25 can testify what he used to get his opinion. 87 1 DOCTOR BREGGIN: Pardon me, sir? 2 JUDGE POTTER: Go ahead. 3 A. What they found was that -- what he found, 4 Doctor Beasley, who is very central in this whole process of 5 evaluation at Lilly, was that 38 percent of patients had had 6 this agitation or activation syndrome; that some patients had 7 a mixed form of it with sedation or quiet in kind of a mixed 8 state, hard to define, and that some patients, a smaller 9 percentage would react the opposite way, that is, they would 10 get more quiet, more somnolent or more sedated, but that the 11 primary effect, the major effect was agitation. And, again, 12 we saw with Mr. Wesbecker that he did get at least fatigued, 13 which many people do on the drug. But, as I said, it may have 14 just been the lithium, most likely. 15 Q. You mean earlier? 16 A. Yeah. The first time. The first time. 17 Q. Now, was that -- do you have the figures there 18 on what kind of agitation was seen in the people taking the 19 sugar pills, that is, the group that weren't given the 20 Prozacs? You say 38 percent on Prozac showed agitation? 21 A. And 19 percent on placebo. But there's two 22 factors that -- 23 Q. So you have a 19-percent difference? 24 A. Yeah. A 19-percent difference or a factor of 2. 25 But you need to really emphasize that this figure of 38 88 1 percent was arrived at without counting the things that are 2 particular to Prozac, too, by not counting manic patients, 3 hyperactivity, nightmares, bad dreams. Bad dreams may not be 4 very common. And I believe that is part of an agitation 5 syndrome. 6 Q. And also when people on placebo get upset, it's 7 not necessarily as severe as the one on a drug. It may be 8 counted as one on a checklist but it may not be as severe. We 9 don't have one way of accounting for that one way or another. 10 Q. Would this also include the same clinical trial 11 of the same people who were going to get concomitant 12 tranquilizing medications for agitation and anxiety? 13 A. Yes. That's an interesting point, that this 38 14 percent includes studies in which a large number of patients 15 were being sedated in order to prevent this from happening. 16 So, I mean, it begins to look like such an overwhelmingly 17 major factor even in the hands of Lilly itself. 18 Q. Continue, Doctor Breggin. 19 A. Now, at this time, other physicians as time went 20 on were beginning to get concerned about it, the clinical 21 investigators and other people and Doctor Heiligenstein, who 22 was involved in this process at Lilly, wrote in a memo that 23 doctors are getting concerned about giving Prozac to patients, 24 quote, who had significant agitation at baseline as a 25 component of their depression. In other words, doctors in 89 1 general, including I think probably his clinical 2 investigators, were beginning to get the same concern that 3 Kapit had, that this drug can worsen depression, especially in 4 the agitative form. And what the decision was, was to, quote, 5 to develop some studies and this could have been related to 6 the Beasley studies, quote, to reassure physicians that 7 fluoxetine could be used in populations of depressed and 8 agitated individuals. 9 Q. Do you know, Doctor Breggin, whether or not 10 there were any studies, any protocols ever done to 11 specifically examine this issue? 12 A. No. I don't believe they ever did it. I think 13 the only thing they did that I know was that in-house study by 14 Beasley with its very dramatic results and I don't believe 15 that was ever promulgated, sent out in any fashion that I'm 16 aware of. 17 Now, at this time, you know, some of the 18 clinical investigators of Lilly were coming, as I said, to 19 these same conclusions. Jan Fawcett, who was actually a Lilly 20 consultant, wrote in an article -- published article, that 21 benzodiazepines should be given with antidepressants if the 22 antidepressant causes jitteriness, and he put in parentheses, 23 fluoxetine. So what he said is you've got to give -- should 24 give sedatives along with antidepressants that when the 25 antidepressant, quote, causes -- this is the quote part, 90 1 causes jitteriness, parentheses, fluoxetine -- and this is 2 under the section on prevention of suicide. It's in the 3 section on preventing suicide in patients. He is suggesting 4 that benzodiazepines be given along with drugs that cause 5 jitteriness and he cites fluoxetine. 6 David Dunner, who was a clinical investigator 7 for Lilly and who in fact in his depo says he's given 50 8 speeches -- paid speeches for Lilly, said that a third to a 9 half of Prozac patients need concomitant medication for the 10 control of sleep and anxiety. 11 In the extreme, Prozac produces mania. The FDA 12 did a study on October 17th, 1986, where they compared the 13 rate of mania -- this is an update. This is an update -- 14 where they compared the rate of mania in Prozac patients to 15 the comparitors, to the other drugs. And they found that the 16 rate of mania in Prozac patients was 1.19 percent. That's 17 more than 1 out of 100 -- 100 people in this room, maybe a 18 little less, 1 on this drug would get psychotic, manic, and 19 all that goes along with that, including you can get very 20 violent on mania. Whereas in the comparitors only 0.3 percent 21 got manic. And one of the interesting observations they made 22 was that in patients who had no tendency to mania, just plain 23 depressed patients, the only ones who got manic were ones who 24 were receiving Prozac; that none of the patients who just got 25 a comparitor drug like Elavil, Tofranil, none of them it said 91 1 got manic if they didn't have a history of mania, but Prozac 2 was provoking manic or hypomanic behavior in patients who had 3 never had it. 4 And here's the quote, it's very important, about 5 the drug's specific tendency in comparison to other drugs. 6 One of the things they had said is all antidepressants produce 7 mania. Well, that's true in a certain percentage of patients, 8 all antidepressants that we know of can produce mania. But 9 here's the FDA's finding that the comparison under 10 scientifically controlled circumstances, over 1 percent, 11 1.19 percent are getting manic on Prozac and .3 on the 12 comparitors, and nobody is getting manic on the comparitors 13 unless they have a history; and on Prozac out of the blue. 14 And here's the quote: All unipolar patients -- 15 that's all patients who just get depressed, not manic. "All 16 unipolar patients who became manic, hypomanic or psychotic 17 were taking fluoxetine; none of those patients received a 18 comparitor substance." 19 Q. This is Lilly clinical trial data. 20 A. This is Lilly clinical trial data analyzed in an 21 update by the FDA on October 17th, 1986. They reviewed, 22 incidentally, 2,938 patients, so we're talking about a 23 substantial review. 24 Q. So this is being seen in the clinical trial 25 experience? 92 1 A. Yes. 2 Q. While the patients are taking the medication 3 under the rules and regulations designed by Lilly? 4 A. That's right. Including taking the sedatives. 5 Q. And being administered by investigators hired by 6 Lilly; is that right? 7 A. Oh, definitely. All this material is coming 8 from doctors who were being paid by Lilly, selected by Lilly 9 to do the research. 10 Q. Well, Doctor Breggin, when you see something 11 like 1.19 percent on Prozac patients versus 0.3 percent, those 12 seem like awfully small numbers to me. 13 A. It's interesting that you raised that because 14 the next card -- we haven't gone through this together because 15 the next card has the numbers, and let me quote you the 16 numbers. They add up. These are real breathing human beings 17 who are getting crazy. 18 Q. Is that a psychiatric term, Doctor Breggin? You 19 may go over our heads here. Be careful not to go over our 20 head. 21 A. It's a translation of the psychiatric term 22 psychotic, and this is what it said on Page 18. Quote, 33 23 reports of mania, hypomania, manic psychosis or psychotic 24 episodes among 2,938 patients treated with fluoxetine, 25 parentheses, 1.19 percent. In contrast, there were four such 93 1 reports among 1,398 patients treated with comparitor 2 substances, .3 percent. So we're talking about 2,938 3 patients, roughly 3,000 people, enough to fill an auditorium, 4 and in the very limited controlled studies by Lilly -- we're 5 talking about a very limited, we're not talking about 6 Wesbecker, who has a lot of history of agitation. We're 7 talking about people in their study. Out of that room of 8 3,000 given relatively short term, a few weeks of this drug, a 9 month or two of this drug, 33 -- 33 out of that almost 2,000 10 people are going to be get severely disturbed and with a 11 disorder that is sometimes associated with violence, whereas, 12 among 1,398 similarly depressed patients who don't get it but 13 who get another drug, only 4. I mean, there certainly is a 14 built-in potential for tragedy here. 15 Q. What should Lilly have done in that situation? 16 A. Well, I think as this data mounted the drug 17 should not have been approved. As you know, I'm not in favor 18 of having it withdrawn from the market now that so many are 19 using it. Many people think it helps. I think there needs to 20 be something else done in the way of warning people but, at 21 this point, we're dealing with a very dangerous substance. At 22 least more studies, more stringent labeling saying that this 23 drug produces this effect in the way that other 24 antidepressants don't. 25 Q. Doctor Thompson yesterday said that there were 94 1 six studies done on bipolar patients. Are you aware of six 2 depression studies done on bipolar patients? 3 A. I'm not. That doesn't mean they don't exist, 4 but I'm not aware of any of those studies. I haven't seen 5 them. I would like to see them. 6 Q. Go ahead. 7 A. Another way to look at what a drug's profile is, 8 what it does, is to look at overdose. If you overdose on a 9 sedative, the concomitant medication they're giving, you go 10 into a coma and you're unconscious and it's like a deep sleep 11 that eventually can lead to death. If you overdose on a 12 stimulant you get hyper and excited. So there, again, we have 13 this easy distinction to make in the extreme, like we did in 14 the animals. And in the 17 cases of overdose reviewed by the 15 FDA, all of whom recovered, incidentally, all recovered, 16 reviewed in late 1986, quote, most prominent findings were 17 hypomania, agitation, restlessness and other signs of central 18 nervous system stimulation. So we get the confirmation as we 19 did in the animal studies that this is the drug's direction. 20 I mean, this isn't even I don't think a debatable item. I 21 mean, the data I think is absolutely overwhelming. 22 Now, as a part of this, as physicians began to 23 get concerned, they began to pressure Lilly for a smaller size 24 pill. They began to say, "We need a smaller pill because 25 we're getting this problem with the usual dose." Lilly wanted 95 1 to maintain -- 2 Q. Well, let me ask you this, Doctor Breggin. Were 3 there provisions in the Lilly protocols themselves to allow 4 their own investigators to reduce dosage if agitation and 5 anxiety occurred during the clinical trials? 6 A. There was what I read to you, a definite 7 statement right in the protocol saying if your patient gets 8 agitated, reduce the dose. However, how are they going to 9 reduce it? It wouldn't be easy because they only had one size 10 pill. To reduce the dose, you'd have to give it every other 11 day, which is hard for people, or as doctors all over the 12 country began to do, empty half the capsule into orange juice, 13 shake it up and give half the dose. Lilly did not produce 14 until much later on after approval, a smaller dose. 15 Q. In September of 1989, there was only a 16 20-milligram pulvule available, isn't that correct, Doctor? 17 A. Yes, sir. 18 Q. The 10-milligram dosage pulvule didn't become 19 available until February of this year; is that right? 20 A. That sounds generally right. I don't have the 21 exact date in my head but it's recent, very recent. 22 Q. You need more water, Doctor Breggin? 23 A. I was just about to say that I'm getting a 24 little hoarse. I'm not used to recitation like that. And 25 partly to spare you and my voice, I had planned to skip some 96 1 of this. 2 Q. Yeah. Can you summarize something or do 3 anything to -- do anything to get the essence of what your 4 findings were in your review of this clinical -- and let's 5 limit it to the clinical trial process now on this syndrome of 6 agitation, anxiety, nervousness, irritability? Anything else? 7 A. Well, I have a bunch of confirmations from 8 within Lilly that doctors outside of Lilly were getting 9 worried about having to give the 20-milligram dose, that is 10 clearly documented within the organization. 11 Q. Now, was this documentation that was received 12 before or after the product was approved or both? 13 A. I believe it's both. Most of the references I 14 have are to just about the time of approval in 1988. In other 15 words, when doctors got some experience with it and it 16 proceeds up through 1990, their concern -- big concern, writes 17 Doctor Heiligenstein, big concern at this time and could 18 become more so, quote, "If there is more media activity that 19 they were concerned about this low-dose issue." 20 Q. All right. Do you have in your analysis -- 21 A. Here's a prior -- excuse me, sir. 22 Q. Excuse me. 23 A. Here's a prior to approval on January 23rd, 24 1987, that's just about a year prior to approval and exactly a 25 year prior to distribution, they have -- well, some discussion 97 1 of it, but I don't have good documentation until it gets out 2 in the public in 1988. 3 Q. Okay. Why don't we -- 4 A. There's one other FDA thing you were asking me 5 about if I could finish up with the FDA, and I'm actually 6 through then with the general discussion of stimulation. Not 7 of suicide and violence. I haven't gotten to that yet. 8 Q. Do that last FDA that you found concerning 9 stimulation and agitation that was found in the Prozac 10 clinical trials. 11 A. In 1986, late '86, the FDA asked to look at why 12 did patients stop taking Prozac because that's another good 13 way to look at what's the problem with the drug, what negative 14 effects does it have on people. 15 Q You mean why people on clinical trials 16 discontinued participating in the clinical trials? 17 A. Yes. There was a very high discontinuation 18 rate, up around 50 percent for the Prozac patients. It was 19 lower sometimes and higher, even with the higher doses, and 20 the most common reasons were the stimulant-like effects that 21 people discontinued, a very high rate of discontinuation, the 22 very high, especially in the light of so often it being 23 thought that Prozac has few side effects, they looked at 1500 24 patients who -- 1500 patients. They found 124, including 6 25 placebo, who they summarized. So now it's a little 98 1 complicated. You've got 1500 patients and now you're going to 2 look at 124 who dropped out for some seemingly serious reason. 3 Of the 124, 118 are on the drug and 6 are on placebo. In 4 other words, placebos, people aren't dropping out. You may 5 get something from placebo that looks like what you have on 6 the drug, but it won't be experienced with the same severity. 7 So placebos are rarely dropping out with serious side effects. 8 Q. What's the significance of that then? 9 A. That even when you look at a figure like 38 10 percent of patients on the drug get hyperactive and 19 percent 11 of the placebo, it doesn't mean the 19 percent of placebo are 12 getting it so severe that they would drop out, for example, 13 but they're getting it as severe as the drug people. 14 Now, of this group of 118 terminators, 44 of 15 them, a very big percent dropped out because of stimulation 16 and agitation. And this actually added up to 2.0 percent of 17 the whole population. So of the whole population of 1500, 2.9 18 percent were dropping out. 19 Q. Because of agitation? 20 A. With agitation or at least having symptoms 21 related to agitation. Many of them, .8 percent of the total, 22 .8 percent of the total, which is close to common; common is 1 23 percent. In the usual definition, if it happens 1 in 100 24 times or less it's called common. Point eight percent is real 25 close to common and I did this myself, by the way. This was 99 1 not done by the FDA. I went through and looked at each of the 2 little vignettes and categorized the people, and when I 3 categorized depression, suicidality, paranoia, mania and 4 irritability, there were 12 people who dropped out for that 5 reason. 6 Q. Out of the 3,000? 7 A. Out of the 1500, and that made almost 1 percent. 8 Again, the seriousness of now beginning to talk about issues 9 of... 10 Q. Now, that's not 1500 people that dropped out, is 11 it? 12 A. No. It's the 1500 that they studied who took 13 the drug, it's 124 who dropped out, 118 Prozac people who 14 dropped out and 12 of them, 12 of them had depression, 15 suicidality, paranoia, mania or irritability, a general 16 complex that we see in Mr. Wesbecker. 17 Q. Still, this is the clinical trials where there 18 is provisions during these clinical trials for if anxiety 19 occurs during the clinical trial to reduce the dosage, if 20 anxiety occurs during the clinical trials to administer 21 concomitant sedatives or sleeping pills; is that right, Doctor 22 Breggin? 23 A. Yes, sir. 24 Q. All right. You say you've examined suicidality 25 to come to some conclusions on this issue? 100 1 A. Yeah. 2 Q. Why would you do that, Doctor Breggin? This 3 needs to be explained to me because I don't understand, 4 because if I'm feeling depressed and worthless myself and 5 feeling like life's not worth living and I commit suicide -- 6 and I will commit suicide, that doesn't mean I'm going to lash 7 out and shoot you or, more significantly, I don't see how that 8 relates at all to what Joseph Wesbecker did when he committed 9 his violent act against other people, even though he committed 10 suicide at the end. What we're talking about here is 11 violence. How can suicide have anything to do with violence? 12 A. Well, there are several ways to look at it. The 13 research that Lilly used to justify developing Prozac, the 14 research on low or sluggish or relatively inactive 15 serotonergic neurotransmission, the theory I suggested to you 16 before that's in many, many, many papers, the theory almost 17 always says that what is going on with the low serotonin is 18 loss of impulse control; that human beings have built-in 19 impulses that control violent action and it's violence towards 20 self or others. I could go through what I just did earlier 21 and produce papers for you. I won't do that. 22 But it was a -- there's a consensus now, 23 particularly in the papers, the research used to justify 24 blocking serotonin, that it -- that that system, when it needs 25 artificial elevation, needs it because with lower impulse 101 1 control you get violence and you get suicide. So that's one 2 reason to be concerned about it. It was almost something that 3 Lilly -- it was something that Lilly should have thought of 4 from the beginning. If we're going to artificially jack up 5 the system, we're disrupting the system. If the system has to 6 do with impulse control maybe while we're helping people, some 7 people are going to react differently than others. They 8 should be very, very concerned especially when it showed up in 9 the animal studies. 10 Psychologically, we talk about violence inward 11 and violence outward; that suicide is a form of violence 12 inward and violence toward others is of similar phenomena, 13 simply directed outwardly and clinicians will say things like 14 behind every suicide is a murder, that is, that the person 15 that is killing themselves is enraged at others and is morally 16 or psychologically inhibited from taking it out on somebody 17 else or through training and education won't take it out or 18 religious principles won't take it out on anybody else, and 19 then breaks another set of principles that is seen as less bad 20 and takes it out on one's self. But it is common to see a 21 person go from one to the other in an inner struggle, and in 22 terms of psychodynamics, it's fairly easy to see the process 23 take place. In fact, one way you help a suicidal person in 24 the therapy setting is by also asking them who they're angry 25 at. And often what will come out is a vision of someone 102 1 they're very upset with being at the funeral and about feeling 2 bad or a parent or a loved one or a spouse who's left, often a 3 spouse who's left and the person saying, in effect, this is a 4 punishment for them when they see what I've done to myself. 5 So, psychologically, violence against self and 6 others often go together and, physiologically, the theory is 7 that they go together and, of course, as you know, from the 8 newspapers alone, mass murderers, people who commit atrocious 9 crimes often at the end turn the gun on themselves. 10 Q. All right. What evidence was there during the 11 clinical trials, Doctor Breggin, concerning whether or not the 12 drug caused individuals to commit suicide or become more 13 suicidal or was an aggravation or risk to some individuals 14 that had that potential to start with? 15 A. Okay. Let me go directly to Lilly's own 16 clinical study of this problem, and then maybe we could take 17 lunch because I'm starting to lose my voice and I would 18 need -- I wouldn't mind breaking soon. 19 Q. Yeah. That's -- 20 A. Go straight through? Go as long as I can. 21 Q. Well, you're going to be here this afternoon so 22 don't wear yourself totally out. 23 A. Let me take a minute first before we look at 24 this because what I'm going to show you is that Lilly knew 25 there was a statistically significant greater rate of suicide 103 1 attempts, physical attempts among the patients taking Prozac 2 than among the control groups of patients taking other drugs 3 and placebo; that, in fact, there was a very significant 4 disproportion. 5 Q. Wait a minute. Wait a minute. Lilly has denied 6 that and say they have statistics, facts to prove you totally 7 wrong, Doctor Breggin. 8 A. Well, I'm going to give you the data. 9 Q. All right. 10 A. I'm going to give you the data. I don't know 11 that this data ever -- I don't think this data ever got to the 12 FDA, maybe the conclusion did, I'm not sure, but the data I 13 don't think ever got there. But before we look at this let me 14 tell you that when we get a statistically significant fact or 15 even an indicator in a controlled trial, it is a hint of 16 disaster, a disaster. Why? Because it is very difficult to 17 pick up events like this in control trials. So if you pick 18 them up, it's a disaster. Let me kind of introduce you to 19 that idea first so that when we get to the facts that this is 20 significant, you'll get how significant it is. 21 Everyone that I have talked to at the FDA, 22 everyone who spoke at the full-day seminar I went to that was 23 put on by the FDA and every -- and a special government 24 analysis of the problem as well as textbooks of pharmocology 25 agree that the control trials don't mean a drug is safe; that 104 1 very serious problems frequently come up in controlled trials 2 after the controlled trials. For example, the government 3 accounting office, the GAO recently did a study of a number of 4 years of what happened before and after drug approval, and 5 they found that -- I think I got the figures exact in my head 6 here, that of 15 approved psychiatric drugs during that 7 period, 9 -- over more than half turned out to have serious 8 events associated with them that had not been realized before 9 and they required major label changes. 10 Q. You mean almost two-thirds of the psychiatric 11 drugs that were approved during that time based on clinical 12 trial data -- 13 MR. FREEMAN: Your Honor, may we approach the 14 bench? 15 Q. It was later determined that that data was 16 simply -- that there was other problems in relation to the 17 drug that caused label changes? 18 A. Yes. And drug withdrawal. 19 (BENCH DISCUSSION) 20 MR. FREEMAN: We object to this line of 21 questioning and move to strike the answer in response thereto 22 upon the grounds that this is not relevant or material and is 23 prejudiced to the case at hand in that the labeling issue has 24 specifically been dealt with by the FDA and has specifically 25 been made on the labeling issue on the subject. 105 1 JUDGE POTTER: If that's the basis for the 2 objection, it's overruled. Why don't you wind him up real 3 quick and we'll go to lunch, you know, on this part. 4 (BENCH DISCUSSION CONCLUDED) 5 Q. We're going to need to take a lunch break, but 6 can we in two or three minutes get to this status on suicide 7 in the Prozac clinical trials? 8 A. Yes. 9 Q. And then we'll come back and expand on that 10 after lunch. 11 A. The clinical investigators for Lilly, that is, 12 their own trained investigators found 12 suicide attempts, 13 reported 12 suicide attempts in the Prozac control groups and 14 2 in the comparitors, 1 in placebo, 1 in the other drugs that 15 were being tried. When they did an analysis of this, they got 16 a statistical value of P equaling .056 and another of P 17 equaling .051. Point 051 is in that statistically 18 positive-range correlation, and so is .056, a little less so. 19 Now, one of the interesting things about how they did this is 20 they didn't count all the patients. In other words, they got 21 a statistically significant-looking result even though they 22 went ahead and excluded 6 of the Prozac patients and 1 of the 23 comparitors, reducing the field from 12 to 2 to 1, which makes 24 it for statistical reasons much harder to show effect in that 25 small a group. So, in other words, they went through and they 106 1 knocked out 12 -- or 6 of the reports from their own clinical 2 investigators and said now we're not going to count them. 3 They didn't go back and ask the clinical investigators why did 4 they do that. 5 Q. Why they called it suicide? 6 A. Why they reported it as a suicide attempt. They 7 just knocked them out. How much data did they have to base 8 the number to knock out and not count 6 suicides. They had at 9 the most 2 lines, 10 words, 15 words. 10 Q. You mean as reported by the investigator on the 11 adverse-event form? 12 A. By the investigator. That's right. The 13 investigator obviously had all the data at his command to 14 decide if a patient had made a suicide attempt and to send it 15 in as such, but he only reports it on these forms in a couple 16 of lines, and that's what the doctors use to second-guess at 17 Lilly and overrule their other reporters. 18 Q. How do you know they didn't call their 19 investigators back and say, "Wait a minute, Mr. Investigator, 20 even though we hired you because you're supposed to be an 21 expert in this field, why did you call this a suicide and it's 22 really not a suicide." How do you know that didn't occur? 23 A. They've said they didn't do it. 24 Q. Oh, okay. 25 A. And it's not anywhere in the report. The thing 107 1 I know for sure is it's not in the report. They just 2 discussed it among themselves, just decided. 3 Q. Got the notes on who those doctors are? 4 A. Well, actually, yeah. I made a mistake. It's 5 actually two doctors who are consultants to Lilly. I 6 apologize. But it was passed through Lilly's offices and 7 approved. I apologize; it was a mistake. Doctor Wenacher, 8 who is a psychiatrist, and Robert Wilson, the consultants to 9 Lilly. 10 Q. All right. 11 A. Now, I want to read you in total the description 12 of two that they -- that the Lilly consultants in their wisdom 13 second-guessed the clinical investigators on and excluded. 14 I'll read it in total. One: This person had no suicidal 15 ideation at onset of study. The patient drank a bottle of rum 16 and then took ten fluoxetine capsules in divided doses of two- 17 hour intervals. 18 Q. So over a five-hour period of time an individual 19 drank a bottle of rum and consumed ten Prozac capsules? 20 A. At two-hour intervals. Now, keep in mind the 21 doctor has a lot more data than this and concluded this was a 22 suicide attempt and they excluded it on those lines. But 23 actually any clinician knows -- and I'm a bit reluctant to 24 have this on television or projected, but the clinician knows 25 that if you want to -- that patients who want to kill 108 1 themselves and have some knowledge of it will space the pills 2 they're taking when they're drinking so they don't vomit. In 3 other words, it shows intent, the careful spacing of the 4 pills, at least, it very likely could. It would certainly if 5 my patient walked in and told me they did this, I would assume 6 they had real intent. 7 The second one they excluded, but they excluded 8 six was -- and I'm going to read you the whole thing. "The 9 patient had suicidal ideation at the beginning of the study 10 and made a self-inflicted laceration of the skin with a razor 11 blade." In other words, all they know is the patient was 12 suicidal to start with and then during the study cut himself 13 with a razor blade. They excluded that one. But even with 14 the exclusions, they came up with statistically significant 15 correlations and, furthermore, one of the consultants, and it 16 was -- my guess is it's the psychiatrist, the chief 17 psychiatrist because that's Wenacher, and he's a very well 18 old-time experienced psychiatrist. Some of his work on 19 depression goes back to the '70s, published reports I've read 20 long before I got involved here by Wenacher going back to the 21 '70s on depression and suicide. He's been writing about this 22 a long time, and what does he say. He's suspicious clearly 23 that Prozac is causing suicide. 24 He writes in his memo to Lilly, quote, a 25 possibility which comes to mind is that fluoxetine might be 109 1 somewhat more stimulating as a drug and that individuals may 2 be slightly more impulsive although their thinking had not 3 changed. In other words, just what I've been explaining to 4 you. The person is thinking about suicide is the same as it 5 ever was. Like Mr. Wesbecker, we don't have any outburst of 6 new problems for him, but the drug is stimulating and lessens 7 impulse control. This is their own investigator, and let me 8 just read it again, because it's written, remember, for Lilly. 9 I mean, this is something they're saying to Lilly. "A 10 possibility which comes to mind is that fluoxetine might be 11 somewhat more stimulating as a drug and that individuals may 12 be slightly more impulsive although their thinking had not 13 changed." And this is in the context of, hey, we got a study 14 here with a lot of suicides in it. 15 Q. Does that complete your analysis of that 16 particular -- 17 A. Well, I just want to point out that, again, this 18 is a study of people who are being sedated when they're 19 agitated. This is a study where it's Lilly's clinical 20 investigators sending in the reports and, furthermore, it's a 21 study in which some of the investigators have even been told 22 by Lilly, by Doctor Beasley's own statements, not to report 23 symptoms of depression as drug effects. In other words, Lilly 24 has told some of its investigators if you get something that's 25 a depression phenomena, which would be like a suicide attempt, 110 1 don't report it as a drug effect. Assume it's the depression. 2 That's what the study is supposed to decide, but they're 3 assuming it, and Doctor Beasley says this in the second 4 volume, Page 155 of his deposition, and it's clear that 5 despite all of the restraints on these studies they didn't 6 even include suicidal patients in the studies. Heavily 7 suicidal, that was one of the things that was ruled out. 8 So we have a study that's not including heavily 9 suicidal patients or patients like Mr. Wesbecker who had some 10 real suicidality in the past, not generally including them; 11 not including people with paranoid psychoses in the past or 12 like Mr. Wesbecker with manic depressive disorder or 13 schizoaffective disorder; it's not including all the high risk 14 people that this drug will eventually be given to. It's 15 including a narrow group of people who are on concomitant 16 medications, many of them. And it still gets 12 suicides in 17 the drug group and only 2 in the comparitor group. And, by 18 the way, if you want to compare the sizes of these two groups, 19 giving Lilly the benefit of the best possible analysis, which 20 is comparing patients' hours on the drug, because, you know, 21 that really gives them the benefit, there were inpatient 22 hours, 3 times as many Prozac as placebo patient hours, yet 23 the rate of suicide is 6 to 1 instead of 3 to 1. That's why 24 it came out significant. 25 MR. SMITH: I think at this point, Your Honor, 111 1 maybe we can have a lunch. 2 JUDGE POTTER: Ladies and gentlemen, we're going 3 to take the lunch recess. As I've mentioned to you-all 4 before, do not permit anybody to communicate with you about 5 this case or any topic connected with this case. Do not 6 discuss the case among yourselves and do not form or express 7 opinions about it. We'll stand in recess till 2:00. 8 (JURORS EXCUSED; BENCH DISCUSSION) 9 JUDGE POTTER: Mr. Smith, what is No. 70? Or 10 Ms. Zettler. 11 MR. SMITH: This was something that was 12 introduced to us. 13 JUDGE POTTER: Wait. Wait. Wait. We've got a 14 Court Reporter that's trying to get this down. What do 15 you-all contend No. 70 is? Ms. Zettler, I'll address it to 16 you since you seem to know more about this. 17 MS. ZETTLER: What I was doing a little earlier 18 was I was examining our computerized testimony from the 19 deposition, it was Doctor Heiligenstein who testified and I'll 20 bring that back with me after lunch, and it was on the part of 21 Doctor Beasley on the actuation issue. I'll bring you the 22 exhibit we used on Doctor Heiligenstein's deposition, as well 23 as the portion of the deposition to establish what that 24 document is. 25 JUDGE POTTER: Is Doctor Beasley one of the 112 1 people that's going to be here live or not? 2 MS. ZETTLER: No. Neither is Doctor 3 Heiligenstein, no. 4 JUDGE POTTER: At this point, I've sustained 5 objections to it being introduced and as far as him just 6 testifying about it, again, I'm really not supposed to allow 7 him to testify about things that are not in evidence or 8 couldn't get in evidence unless I kind of feel they're 9 trustworthy. It kind of sounds like it was just straightening 10 things out about this document. Until I see more, will you 11 instruct him not to talk about this? And, Mr. Freeman, if you 12 want to go into it on your cross, you're certainly free to do 13 that. I don't want to hear the number 38 percent again until 14 I figure out where it came from. 15 MS. ZETTLER: I'll bring it. 16 MR. SMITH: I apologize. 17 MR. FREEMAN: We had a motion to strike all of 18 his testimony on the subject where he read from the document. 19 JUDGE POTTER: I really don't know how I do that 20 with the jury. It's in. You know, it may go away. They may 21 convince me that it's a reliable document, but right now I'm 22 not convinced it is a reliable document. Somebody said it was 23 published at one point. 24 MR. SMITH: Your Honor, what makes us think it's 25 a reliable document is the stamp of PZ number. It was Bates 113 1 stamped with their PZ number. I'm a little bit -- ds 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 113 1 JUDGE POTTER: Well, the point is is my memory 2 of it, and Ms. Zettler can probably confirm this, you got 3 everything from get-well cards; they went through these 4 people's desks and cleaned them out and PZ-stamped stuff. I 5 bet you've got notes from girlfriends and drafts. 6 MS. ZETTLER: Nothing exciting, Judge. 7 JUDGE POTTER: No, but what I mean is that -- I 8 don't know what you've got, but I was assuming at some point 9 somebody was going to show me a Xerox out of the journal of 10 something or another that would be 90 percent of that 11 publication. 12 MS. ZETTLER: After lunch I will bring you the 13 testimony from Doctor Heiligenstein that will establish that 14 as a reliable document. 15 JUDGE POTTER: I need that before I hear 38 16 percent again. 17 (LUNCH RECESS; BENCH DISCUSSION) 18 JUDGE POTTER: Over the lunch break my sheriff 19 got two more questions from the jurors, and it strikes me that 20 the one dealing with Exhibit No. 38 is probably not something 21 this witness can answer. 22 MR. SMITH: We're getting 38 out and, you know, 23 if it's apparent from the document... I think probably Doctor 24 Breggin will say he doesn't know, hasn't seen any. 25 JUDGE POTTER: What I'm going to do on that one 114 1 is both of you have it, and if you find an opportunity to ask 2 those questions, what are the effects of lithium and Restoril, 3 you can probably do that. But the first one, you-all will 4 just have to find an appropriate witness if you want to. 5 Mr. Smith, do you have any problems with asking 6 him about the animal studies or does he know? 7 MR. FREEMAN: No. That's fine. 8 MR. SMITH: See, this may not be unusual in 9 Kentucky but -- 10 MR. FREEMAN: I've never had this happen. I've 11 had one question in 30 years. 12 MR. SMITH: We always get questions in Texas 13 when the jury goes out to start deliberating. 14 JUDGE POTTER: We get those, too. And really I 15 wouldn't have said that much about it. I normally don't 16 mention it, but this is such a long trial. 17 MR. SMITH: And it's complicated. 18 JUDGE POTTER: But, quite frankly, I hoped I 19 would scare them out of doing it. But when they passed our 20 new evidence code they actually put it in the evidence code. 21 MR. SMITH: They have the absolute right to do 22 that. 23 JUDGE POTTER: Believe it or not, I have the 24 right to ask questions and call witnesses. You want me to 25 scare you to death? 115 1 MR. SMITH: You remember the famous line from 2 the verdict, don't you, where Paul Newman was having trouble 3 proving his medical malpractice case and the old cranky judge 4 hated him, just hated him. And the judge started asking 5 questions, and Paul Newman says, "Judge, if you're going to 6 try my case, please don't screw it up." 7 (BENCH DISCUSSION CONCLUDED) 8 SHERIFF CECIL: The jury is now entering. All 9 jurors are present. Court is back in session. 10 JUDGE POTTER: Please be seated. Ladies and 11 gentlemen of the jury, some of you have on occasion given me a 12 question, or given my sheriff a question. Sometimes I have, 13 you know, just asked the question myself, but what I do more 14 than -- often than not is I just give that piece of paper to 15 the attorneys and one or the other of them at some point 16 during the trial will try and answer that question through a 17 witness, because sometimes you've asked a question that maybe 18 this particular witness might not have any knowledge of. And 19 then it also might be a question that between the attorneys 20 and myself, we've decided it can't be asked and you'll never 21 hear the answer. But I just want to tell you that's the way 22 your questions are -- the few I've gotten, have been handled. 23 Some of them -- like I think it was yesterday or 24 the day before just right when we started I asked the witness 25 the questions because they were quick and simple. Some of 116 1 them have been handled to where I just turned it over to the 2 attorneys and one or the other of them said, "Judge, in the 3 appropriate time I will get that information in the record. I 4 just want you-all to know that's the way they've been handled. 5 Doctor, I remind you you're still under oath. 6 Mr. Smith. 7 Q. Doctor Breggin, since we've had these questions 8 from the jurors, I'd like to hand you three documents; one has 9 been marked Plaintiffs' Exhibit 37, which I believe is the dog 10 study -- yeah, dog study, I believe, that you referred to 11 earlier; the other is Exhibit 38, which refers to monkeys, I 12 believe on the third page; and the other is Doctor Slater's 13 cat study. And I'm going to give you those documents so maybe 14 with those documents totally in front of you -- and I 15 understand that your reference to your note cards you don't 16 have the entire document in front of you when you made that 17 notation earlier; is that right? 18 A. Yeah. I worked from the entire document but I 19 couldn't possibly bring them all here. 20 Q. All right. One of the questions is in 21 Exhibit 38 -- do you have that in front of you? 22 A. I have 37, 38. 23 Q. On the last page in the last paragraph it's 24 mentioned that blood tests on monkeys would be reviewed and 25 additional studies were planned. Do you see that? 117 1 A. Right. 2 Q. Do you know of your own personal knowledge or 3 from your review of the Prozac documents and the FDA files 4 whether or not, A, there were additional studies done on 5 monkeys and, B, what the results were? 6 A. No. I didn't look at just simple lab data; I 7 only looked mostly at the behavioral data. So I wouldn't know 8 whether they did additional studies of blood chemistries. I'm 9 not aware that they did any behavioral studies on monkeys. 10 Q. All right. So you were keying toward, when you 11 followed up on that, to see if there were any follow-up 12 studies that recorded the behavior of these higher primates? 13 A. Right. I have no idea whether they pursued the 14 blood chemistry studies further. No idea. 15 Q. Now, when they're talking about additional 16 studies there on monkeys, they're talking about something 17 pretty specific, aren't they, Doctor Breggin? 18 A. Yes. I mean, they seem to be talking about 19 something that might or might not have had any relevance to 20 the kinds of issues in the case. 21 Q. All right. Specifically, the white count? 22 A. Yeah. Excuse me. 23 Q. The next question, and I don't think you'll need 24 any of the documents for that. This question is to -- was, 25 what are the adverse effects, if any, of lithium and Restoril? 118 1 Obviously, I'm sure that question arose because, as we'll see 2 in the medical records, Mr. Wesbecker was, at the time of this 3 shooting, taking lithium for sure and potentially Restoril. 4 MR. FREEMAN: Could we have them one at a time, 5 Your Honor? 6 JUDGE POTTER: Okay. 7 Q. Start with lithium. Why don't you describe 8 generally basically what lithium is, Doctor Breggin. 9 A. All right. Lithium is a metallic salt. It 10 occurs in nature but not in the body in a functional way. The 11 only way it appears in the body is as, in a sense, a 12 contaminant from soil or something else. It doesn't have a 13 known function in the body. It's been known for a long time 14 as a toxic element. Then in the 1930s, it was discovered that 15 giving it to animals and then to people in mental hospitals 16 seemed to quiet them, seemed to control their moods or steady 17 the mood. And it's been used particularly in the last few 18 decades, particularly to control people who have manic 19 episodes, in particular to control them when the episodes 20 aren't so severe or in between the episodes. 21 If someone is in a very full-blown manic 22 episode, they might use a more hard-hitting drug to stop it, 23 like Haldol, a neuroleptic drug, but then try to keep the 24 person in a more even mood with less ups and downs by giving 25 the lithium. It is approved by the FDA for manic depressive 119 1 disorder. Some people think it also helps depressed people 2 just by not letting their moods get so intense. Some clinical 3 data, a little bit of research suggests it may help with 4 violent moods, that it might be -- just by I think by its 5 dampening effect may help the violent moods. There have been 6 some studies in prisons on that, for example. But it hasn't 7 been approved for that; there's not been overwhelming 8 evidence. I see it in my practice, though. 9 This is a drug that can take away the intensity. 10 It has many complex effects on the nervous system. It 11 replaces sodium and potassium. The brain confuses it with 12 sodium and potassium, and when it gets into the process of -- 13 and sodium and potassium are what help the electrical impulse. 14 They have to do with the electrical impulse going through the 15 nerves. And so you get a slowing down of neurotransmission in 16 general, not by hitting the receptors but by interfering with 17 the process of electrical movement down the long arm or axon. 18 Other effects, as well; it's a widely used drug. 19 The major side effects of the drug are there's 20 frequent skin problems, significant percentage of people will 21 have thyroid problems, get hypothyroid. There's a lot of 22 research and yet it's still debated about kidney disorder. 23 There are many reports of kidney disorders, some disagreement 24 about that. People can lose their hair taking lithium; that's 25 another one of the side effects of it. 120 1 Probably the most important side effect is the 2 fact that it's a drug that is borderline -- that makes the 3 patient often borderline toxic; that is, this is a drug that 4 you have to give to a level sufficiently high that you're also 5 risking going into a more toxic state; not a behaviorally 6 toxic state where you do anything, but a state in which the 7 central nervous system isn't functioning very well, and in 8 that process and also along with its other side effects, you 9 can get nausea and vomiting, which is also on the side 10 effects, and tremor, which is also on the side effects, but 11 then it can build up to a more serious state of depression, 12 pushing down. The opposite of stimulation phenomena, pushing 13 down on the central nervous system in overdose, and that can 14 be very serious. 15 So patients -- to avoid people from becoming 16 toxic on lithium, patients have their blood tested regularly 17 for a lithium level, and the generally sought level is .8 18 milliequivalents per liter in the blood, .8. And we'll see at 19 one point he gets to a 1.5, which is considered in a toxic 20 range. 21 Q. When you say "he", you mean Mr. Wesbecker? 22 A. Mr. Wesbecker gets a 1.5 when he's taking Prozac 23 the first time. Many people take this drug for years and 24 years and years and, recently, I've been seeing patients in my 25 practice having concern about they may get some memory 121 1 problems for being on the drug for a long, long time. 2 That's maybe too much information, but that's 3 the general picture of what the drug does. It's not exactly 4 sedating, although it can have a sedating affect. It's more 5 like clamping on the mood, controlling the range of mood. 6 Q. Why don't we just address the question now, 7 since it's been raised. Was Mr. Wesbecker's lithium levels 8 that I believe were reviewed in tox findings at his death, 9 were they out of kilter or abnormal or is there any reason to 10 believe that the lithium had anything to do with Mr. 11 Wesbecker's actions? 12 A. Oh, it definitely didn't have anything to do 13 with worsening them, I mean, absolutely not. If it did 14 anything, it helped keep him from getting so agitated. In 15 other words, there would have been a tension, perhaps, 16 between -- a tension between the stimulant effects of the 17 Prozac and the quieting effect of the lithium. But if I get a 18 chance, when I take you through some of the clinical studies 19 on what happens to patients, you'll see some patients get very 20 out of control on Prozac, even though they're taking lithium. 21 So there's actually literature reports of people getting very, 22 very angry and hostile and disturbed that seem due, in the 23 investigator's minds, to Prozac, but they were on lithium. So 24 lithium has its limits; it's just not a total control 25 mechanism, but it would go in the direction of containing the 122 1 mood rather than stimulating. 2 Q. And is it your recollection that Mr. Wesbecker's 3 lithium levels were in the appropriate ranges at the time of 4 his death? 5 A. Yes, the lithium level. He seemed to always 6 take his medicine pretty much as prescribed. Even when he was 7 very upset, he often took it as prescribed, I'm sure not 8 always. And he seems to have had a normal range for the 9 lithium level, acceptable range. 10 Q. Restoril. Describe to the jury what Restoril is 11 and the question is what are the adverse effects of Restoril, 12 or is it Restoril? 13 A. Restoril, temazepam. This is a drug that is 14 designed as a sleeping pill, hypnotic in the technical 15 language. It is a drug that depresses central nervous system 16 functioning, as a general way of putting it. And you can 17 think of it in some ways, well, just like your general 18 knowledge of a sleeping pill would be, that you take it and it 19 tends to relax you and ultimately to puts you to sleep; in 20 fact, injectable short-acting forms are used to put people to 21 sleep at the start of surgery. You have closely related drugs 22 just to give you an injection and put you to sleep. It's a 23 classic sedative -- it's a classic hypnotic, sleep-inducing 24 medicine in that regard. It was tailored to have a short 25 half-life. It has a half-life of nine hours. 123 1 Q. What's the importance of that, Doctor Breggin? 2 A. It means that within the time you've been 3 sleeping -- say if you take the pill an hour before you go to 4 bed and you get up after an eight-hour sleep, you've had about 5 nine hours of pill, and roughly half of it only would be left 6 in your bloodstream, so by the time you're supposed to wake up 7 and go to work, you can hopefully drive, shave yourself 8 without cutting yourself, not have the problems that go along 9 with being sedated, which can be incoordination, lack of 10 quickness. This is the classic where they put the sticker on 11 your bottle, don't use machinery and don't drive your car, or 12 at least think about driving your car beforehand before you do 13 this, because it produces varying degrees of this kind of an 14 incoordination, slowing down and sleepiness. But it was 15 tailored specifically not to go through the rest of the day 16 and reduce anxiety. It's purposely not tailored for that; 17 it's purposely tailored to have a shorter acting time. 18 The dose that he took was either 15 milligrams 19 if he was taking one pill, and that's your starter dose, and 20 that's what it was recommended for. When the doctor wrote the 21 prescription, he said one pill at night; h.s. is the Latin for 22 at night or before sleep, and it was written to take one. 23 I looked over the prescriptions and it looks 24 like he might have used them at the rate of two sometimes, and 25 that would be typical, even though the doctor only writes one 124 1 at night, for the doctor to say one or two to the patient. So 2 I wasn't surprised to see that it looked like some nights he 3 might have been taking two. Two would have brought him to the 4 30 milligrams, which is also a normal sleeping dose for the 5 drug, and we would expect by the next day that he would not be 6 getting an anti-anxiety effect. 7 We've been talking about concomitant 8 medications, taking tranquilizing drugs. He would have to be 9 taking that drug four times a day to maintain a tranquilizing 10 effect during the day because it's tailored for that nine-hour 11 period at night and is marketed -- and this is important -- it 12 is strictly marketed as a sleeping pill, not a daytime 13 quieting agent, very specifically marketed in that manner and 14 classified in that manner in pharmacology texts. 15 I've told you a lot already about the basic side 16 effects of the drug. It is habit forming. It is in larger 17 doses addictive, and in larger doses it can be abused and can 18 give you withdrawal symptoms. At a dose level of 15 or 30 19 milligrams a night, the most likely negative effect is simply 20 that its effect wears off so that you get -- it's helpful for 21 a few weeks, but after a while you really may not get that 22 much help from the pill. They're actually usually recommended 23 only for two or three weeks at a time because there is the 24 tendency for the brain to react. Remember I told you about 25 how the brain reacts against Prozac? It also reacts against 125 1 this kind of a heavy medication. But many people just take it 2 for years on end with no seemingly bad effects. 3 Q. Well, I guess the question is, is it your 4 opinion whether or not it was Prozac that caused Joseph 5 Wesbecker to do what he did on September 14th, 1989, or a 6 combination of Prozac, Restoril and lithium? 7 A. I would say with certainty or near certainty 8 that the drugs he was taking, if anything, helped a little not 9 to react to the Prozac. They certainly didn't cause the 10 problem. In the clinical studies, many patients on Prozac 11 were taking a sleeping pill, because it causes insomnia. So, 12 in effect, he's getting a pill for his insomnia which could 13 have been worsened by the Prozac. And we'll get evidence 14 later that despite the Restoril, his insomnia got worse on the 15 Prozac. Not really surprising. The lithium again, would 16 have, if anything, evened him out some. Neither one is 17 contributing to what happened to him. 18 Q. All right. The other questions are what dose 19 was given to the animals, large dose versus low dose. And I 20 believe this has to do with the -- well, why don't you 21 identify it in the cat studies and the dog studies. 22 A. And the rat and the mouse studies. The dog 23 studies were, as I mentioned to you, high doses. The dogs 24 were getting 20 milligrams per kilogram. A kilogram, if my 25 memory doesn't fail me, is 2.2 pounds? 126 1 Q. Don't ask me. 2 A. I'll go with 2.2 pounds per kilo. So that means 3 that if the dog is a relatively small dog, a ten-pound dog or 4 let's say a five-kilo dog, he's already getting five times the 5 dose of a human being's starting Prozac dose. He's getting a 6 big dose. 7 I don't have data on all the mice and rat 8 studies. The rat study was described as a high dose. I think 9 it was a toxic study, again. The mouse study I think was 10 lower, as I recall. The mouse study was being fed in food, 11 and I don't think it was toxic, but I'm not absolutely clear. 12 And I have to review the Slater study to tell you what the cat 13 dose is. So if you give me a moment, I'll look at the Slater 14 study. 15 Q. If you can find it real briefly; otherwise, 16 we'll have you take a look at it either at the break or 17 tonight. 18 A. Here we are. A five-day course of 1.25 19 milligrams per kilogram and 5 milligrams per kilogram. 20 Remember I told you earlier that the cat study where they got 21 angry -- inexplicitly angry and menacing was not a toxic 22 high-dose level, so some of these cats at least are getting 23 a -- are getting doses of 1 per kilogram and another time 2.5 24 and another time at 5. The cat studies were not high-dose 25 studies, though I could probably spend more time getting it 127 1 more exactly. 2 Q. Was this increase in dosage that we've seen in 3 some of these animal studies, was this due to the size of the 4 animals, that some animals were getting larger doses, or were 5 the Lilly scientists moving up into toxic points with this 6 dosage? 7 A. Well, the FDA requires toxic dose studies to 8 find out what the toxic dose is. In the case of Prozac, it is 9 a relatively safe drug in that regard in terms of killing 10 yourself with it. That's one of the things that wanted to be 11 found out. And also you want to see what's the effect on the 12 liver and the spleen and other organs. And just as I said to 13 you, that in behavioral studies with a larger dose, sometimes 14 you can see an effect you might miss with the smaller; 15 similarly, by giving the larger physical doses you may see an 16 effect on the liver that otherwise might have taken you ten 17 years to find in the lower animal studies, so they're 18 purposely giving large doses to the animals. In none of these 19 studies were they particularly trying to find out if the 20 animals got aggressive or irritable; that just happened to 21 turn up and get reported. 22 Q. Were these doses -- this is the last question, I 23 believe. Were these normal or abnormal dosages? 24 A. In the dog study, very abnormal, abnormally high 25 studies; in the cat study, it's more in the normal range. 128 1 Q. All right. Now, I believe, Doctor Breggin, 2 before lunch we were talking about suicide and the incidence 3 of suicide in the Prozac clinical trials and the significance 4 of that. Where are you? Are you ready to tell us about some 5 more studies, or where should we go next? 6 A. Well, I would like to ask your patience for one 7 more brief session of note cards, because it's one more area 8 that I want you to get detail in, and that's Germany and 9 England's evaluation. I've shown you that the FDA's main 10 investigator compared the drug to amphetamine and that he and 11 his boss both saw this drug as having very stimulant and 12 agitating qualities, including irritability in the definition 13 of agitation. In Germany -- and also that Doctor Kapit saw 14 that the drug could worsen depression or at least predicted 15 that it was likely to worsen depression, enough so, he wanted 16 it in the label at one point. 17 Well, the same things seemed to have happened in 18 Germany and in England, except in Germany it resulted in a 19 label change, in a very specific requirement recommended, not 20 enforced necessarily, but recommended. It resulted in the 21 recommendation that in the early weeks, patients at suicidal 22 risk should be given benzodiazepines on a regular -- for 23 anxiety. Now, that doesn't mean for sleep. Restoril is a 24 benzodiazepine but short acting, tailored for sleep, given at 25 night. They're talking about something more like Valium, and 129 1 they're talking about several times a day, because that's how 2 you treat anxiety, by giving the drug several times a day to 3 keep the level up. 4 Germany's FDA equivalent is called the BGA. I 5 don't read German and my access to files on this one is much 6 more limited than the FDA, where I had cartons and cartons of 7 material. Here I have English language memos, all of which I 8 believe were produced from Eli Lilly corporation at the 9 request of the attorneys, as far as I know virtually all of 10 them were. And I had not seen these, incidentally, this 11 material at the time that I concluded it was a stimulant. In 12 fact, I hadn't seen the FDA internal studies at the time I 13 concluded it. I concluded it was a stimulant; Kapit concluded 14 it was a stimulant; Germany concluded, all separately. In 15 fact, I don't think any of us knew about each other. I don't 16 think Kapit knew about Germany, even though this happened 17 beforehand. I'm not certain of that. 18 The one piece of data is a memo from Doctor 19 Schenk, who is an employee of Lilly corporation in Germany, 20 and it's -- and it's also Doctor Weber, who is an employee, 21 and it's in 1984, early in '84. And they're talking about 22 problems they're having with the BGA, what the BGA is saying 23 to them. First of all, the BGA is saying there's a 24 disagreement between patients and doctors in the evaluations, 25 that the patients tend not to approve of the drug, while the 130 1 doctors do in their rating sheets. 2 And then it says, quote, there have been a few 3 patients complaining of psychosis and hallucinations, end 4 quote. And then, quote -- this is the Lilly German employee 5 in 1984. "The BGA suspects fluoxetine to be a stimulating 6 activating drug (side-effect profile, suicides, suicide 7 attempts)." And it says, talking about suicide from Prozac it 8 says, "This is a very serious issue in the opinion of the 9 BGA." And back in '84, it says it may well be that we will 10 have to recommend concomitant tranquilizer intake for the 11 first two or three weeks in the practice literature, that is, 12 in the literature about how to practice in Germany. 13 In another memo, May '84 -- I'm sorry. This is 14 a direct continuation, and it talks about the concern that 15 there is an increased suicide rate and that the drug may be 16 worse -- I'm paraphrasing now -- and that the drug may be 17 worsening the condition, producing, quote, a deterioration of 18 the clinical condition. 19 At this point the BGA is very worried and it 20 says that -- it says, quote, considering the benefit and the 21 risk, we think this preparation totally unsuitable for the 22 treatment of depression. Now, eventually they would change 23 their minds, but this is in 1984. 24 In another Schenk memo, this time to Zerbe, who 25 is with Lilly in Indianapolis, this is a memo from German 131 1 Lilly to American Lilly, and it concludes, quote, if the drug 2 is used according to the revised package literature; i.e., in 3 agitated and suicidal patients only together with concomitant 4 sedative drugs, there should be no doubt on fluoxetine's 5 positive benefit/risk ratio in the treatment of depression. 6 So the Lilly people are saying we should erase the doubts the 7 Germans have if we agree to this. 8 Now, interestingly enough, Doctor Beasley, who 9 was making -- later makes an analysis of suicidality in Lilly 10 in America, says he didn't know about this stuff, at least 11 that's how I understand what he's saying in Volume II, 12 Page 192 of his depo. 13 And the discussion continues to talk about the 14 danger of activating antidepressants and how they should, 15 quote, only be used with caution in suicidal patients, at best 16 with concomitant administration of sedating drugs. The latter 17 can be omitted at the time of sufficient mood elevation. This 18 is the memo by the German Lilly employee. 19 Another memo by a BGA employee, Doctor Schmidt 20 in '85, about a year later now, and it's a letter that's 21 called an intend-to-refuse registration letter. They're 22 intending to refuse to allow the drug and they raise the 23 issues we're talking about. They say it's been insufficiently 24 tested, the profile of action, not been characterized in 25 hospitalized patients. That's the same in the U. S., but it's 132 1 approved in the U. S. without its being tested, by I think 2 two, that I could find, two protocols, and they weren't 3 placebo controlled and they weren't used by the FDA for 4 approval. It says long-term effect is not established -- and 5 I don't believe there ever was -- and then they talk about 6 the, quote, the justified suspicion that they have 7 unacceptable damaging effects. 8 And this is what is said on 2.1 paragraph, the 9 Paragraph 2.1, memo from the BGA, the use of the preparation 10 seems objectionable as the increase in agitating effect occurs 11 earlier than the mood-elevating effect and, therefore, an 12 increased risk of suicide exists, end quote. So, in other 13 words, the drug agitates fast before the person feels less 14 depressed, increased risk of suicide. 15 And then it says what Kapit was saying about the 16 worsening of depression, Paragraph 2.2. Quote, during 17 treatment with the drug, some symptoms of the underlying 18 disease (anxiety, insomnia, agitation) increase, which as 19 adverse effects exceed those which are considered acceptable 20 by medical standards, just too agitating by medical standards. 21 Seven years later the problem has continued. 22 Q. Wait a minute. Seven years later? 23 A. 1991. 24 Q. So this would be after the BGA had in fact 25 approved Fluctin, or Prozac, in Germany? 133 1 A. I have off the top of my head that the approval 2 date is 1992, but I could be off on that. 3 Q. I think actually we've already -- it's already 4 been established that it was approved in 1990. 5 A. 1990. 6 Q. Late '89, put on the market early '90. 7 A. Okay. 8 Q. But it may have been that -- 9 A. Well, this is more striking then, because in 10 1991 they're now wondering if it's an amphetamine. 11 Q. What do they say about that? 12 A. This is from Hans Weber, the Lilly person in 13 Germany, to Ray Fuller, the highest ranking scientist at 14 Lilly. It's dated February 6th, 1991, and it's about a BGA 15 meeting. And it talks about the concern about suicidality. 16 And it says, quote, the question was raised whether fluoxetine 17 could be an amphetamine like drug, which may explain 18 stimulating and anorexic effects. Anorexia means loss of 19 appetite. It turned out that not enough was known about the 20 pharmacology in this respect. 21 I think that what Doctor Weber is saying is that 22 he doesn't agree and he's going to explain to them all these 23 years later why it's not an amphetamine, and an argument 24 follows about it that he makes, saying that, well, the way it 25 suppresses food is somewhat different from the way -- food 134 1 intake is somewhat different from the way the amphetamine 2 suppress it; chemical structure is different, that's certain. 3 Q. You say that's certain that the chemical 4 structure is different? 5 A. Yeah. Robert Thompson writing to the top 6 scientists, Fuller and Wong, in February 1991, again about the 7 BGA, confirms that there is, quote, question/concern that 8 fluoxetine may have an amphetamine like activity. 9 Now, with all of this data now, BGA, U.S.A., and 10 I might throw in that England, their CSM raised the same sort 11 of issue. They were thinking about contraindicating it in 12 underweight, agitated or anorexic patients, though they did 13 not. There was concern everywhere, that it seemed to me that 14 Lilly should have, but I find no evidence, really, really done 15 an investigation of whether this was a stimulating agitating 16 drug and what the dangers were. 17 Q. Well, what kind of investigation? Why couldn't 18 they just go back and look at their clinical trials? 19 A. Well, they did go back and look at their 20 clinical trials, and Doctor Beasley concluded that it was a 21 very activating drug, and then didn't apparently do anything 22 about data. But they also should have been looking at, hey, 23 what if we didn't have the concomitants? Because not 24 everybody, like in Mr. Wesbecker's case, the doctor is going 25 to -- Doctor Coleman knew that it was a somewhat stimulating 135 1 drug so he was probably glad the patient was on Restoril at 2 night for sleep, but he didn't know that Germany had 3 recommended it as a daytime anti-anxiety drug to be given to 4 patients who had any potential like this. He didn't know 5 that -- 6 MR. FREEMAN: Your Honor, I think it's improper 7 to say what Doctor Coleman thought. Can we move to strike? 8 JUDGE POTTER: Well, sustained. 9 A. Excuse me. The final BGA information concerning 10 use says, under risk patients, risk of suicide, Fluctin, 11 that's Prozac, does not have a general sedative effect on the 12 central nervous system; therefore, for his or her own safety, 13 the patient must be sufficiently observed until the 14 antidepressant effect of Fluctin sets in. Taking an 15 additional sedative may be necessary. This also applies in 16 cases of extreme sleep disturbance or excitability. I've 17 already cited what the CSM in England at least considered and, 18 honestly, I just was not able to obtain any further data on 19 England; I just wasn't able to get it. 20 Q. All right. 21 A. I think that should conclude the general 22 presentation on the subject that this is a stimulating, 23 amphetamine like drug that the FDA's most knowledgeable person 24 concluded this; that the BGA pretty much seems to have 25 concluded it; that England was worried about it; that 136 1 clinicians are acting as if it is, including clinicians who 2 know something, who are experienced through Eli Lilly as 3 clinical investigators and, also, that animal and human 4 studies are confirming this whole package, including some 5 hints -- and we'll get more data now as we go along -- some 6 hints, suggestions that it produces aggression as stimulant 7 drugs tend to. 8 Q. All right. Have you prepared a chart to 9 demonstrate the stimulant profile? 10 A. Yes. I developed two charts, one to develop a 11 stimulant profile to show what it looks like, and the other -- 12 Q. Don't you think we should do that first? 13 A. Yeah. Okay. 14 Q. Or do you? 15 A. No. That's fine. Let's do that first. 16 MR. FREEMAN: We've never been shown this 17 document, Your Honor. 18 MR. SMITH: Before we do that, can you identify 19 the handout, Exhibit -- 20 JUDGE POTTER: Wait just a second, Mr. Smith. 21 (BENCH DISCUSSION) 22 JUDGE POTTER: Mr. Freeman? 23 MR. MYERS: Judge, I don't believe that this was 24 in the package of materials for enlargements and demonstrative 25 evidence that was given to us before the trial as something 137 1 they were going to put into evidence, and that's what they're 2 trying to do. 3 MR. SMITH: It's something that he just prepared 4 last night, same way they've been doing with demonstrative 5 evidence that they've never submitted to us, like you did 6 yesterday with Doctor Thompson. No difference. 7 MR. MYERS: Like what? 8 MR. SMITH: All of those charts that you had 9 that you were displaying to the jury. 10 MR. MYERS: Those were given to the Plaintiffs 11 before the trial started. 12 JUDGE POTTER: Is it -- 13 MR. SMITH: It's merely a summary of the data. 14 MR. MYERS: It doesn't say where it's from, 15 Judge. 16 JUDGE POTTER: Where is it from, Mr. Smith? 17 Where does 14.9 percent come from? 18 MR. SMITH: These figures are from the PDR. 19 JUDGE POTTER: I tell you what, these things 20 have not been produced to the Plaintiffs (sic) ahead of time; 21 is that right? 22 MR. MYERS: I've not seen this before. If he 23 says they come from the PDR, I guess we'll see. 24 JUDGE POTTER: Put your enlargement up and let 25 him talk from it, but as far as giving it to the jury, I'm 138 1 going to sustain the objection. 2 (BENCH DISCUSSION CONCLUDED) 3 Q. What we're going to do, Doctor Breggin, is just 4 go through this chart at this time. Come down here. 5 Q. Do you have a stimulant profile described there, 6 Doctor Breggin? 7 A. Yes. This is a chart that I made to show the 8 stimulant profile of the drug. All of the data on this 9 particular chart where I have numbers are taken from the 10 clinical trials. And kep in mind that numbers in the clinical 11 trials are going to be much more -- much lower for this than 12 in actual practice. 13 Q. Now, where did you get the clinical trial 14 numbers? 15 A. The clinical trials numbers are taken right from 16 the label. I think I got all these from the label. That is 17 from the -- from the label that Lilly and the FDA worked out 18 together, and that was approved by the FDA. 19 Q. All right. Why don't we just -- 20 A. Why don't you hold up on that a minute. 21 Q. I'm asking the questions here, Doctor. I just 22 want to hold this up so we can confirm -- 23 A. Oh, that's good. 24 Q. -- that we're using the same percentages. 25 A. It's such a serious matter, I apologize. 139 1 Q. I apologize. 2 A. It's hard to deal with and it's easy to have a 3 little break, but it's so serious. This is the Lilly chart 4 that on many occasions was said by the FDA to be too full of 5 noise; that is, that a Doctor looking at this chart would have 6 a terrible time realizing what was going on, and you can see 7 the noise. You can see -- here are -- let me explain this 8 chart. Here's placebo, 799 patients in the controlled studies 9 and here's Prozac, 1,730 patients in the controlled studies. 10 Q. To get this clear, this is not your chart? 11 A. This is from the label. By the way, an 12 interesting bit of information that pops up that I didn't show 13 you before, you can see that this 800 and 1700 is roughly half 14 as many people got placebo but suicides were six times as 15 much. 16 Q. Say that again? 17 A. Suicide attempts in that report I looked at with 18 you were six times more frequent in the group of 1730 than in 19 the group of 799; in other words, very disproportionately 20 high, because I remembered I hadn't given you those numbers. 21 so Lilly created this chart with a lot of back and forth and 22 back and forth and with the FDA saying I wish you'd make it 23 simpler and at times suggesting they do a stimulant chart. 24 Finally this is what went in. 25 And you'll notice that it has a lot of stuff 140 1 that is insignificant where there's no difference essentially 2 between the drug and the placebo. In fact, except for 3 asthenia, which means lack of will and vitality, very closely 4 related to depression -- if you had asthenia you could just 5 simply think you were depressed -- except for asthenia, all 6 these numbers are basically alike. They're not significant. 7 If you did a study of significance, this would be a random 8 distribution, yet they're all in here. 9 Q. All right. Let's just take, for instance, 10 laryngitis. 11 A. Pharyngitis. Pharyngitis is inflammation of the 12 throat. I have a bit of that from talking so much more than 13 I'm used to. Pharyngitis is in 2.7 and 1.3. It's, as I 14 recall it, was not -- they ran some tests of all this stuff, 15 sinusitis. 16 Q. Does Prozac cause sinusitis? 17 A. Nor pharyngitis or nasal congestion or headache, 18 specifically sinus headache. 19 Q. Why would they be putting something in the label 20 concerning those type of symptoms, these type of conditions 21 that are clearly not related to the use of Prozac? 22 A. All I can say is that the effect of it is that 23 you don't see this. 24 Q. All right. Now, describe what you have there, 25 Doctor. 141 1 A. What I have done here, with the exception of 2 akathisia, is to take the significant side effects, the ones 3 that showed up significantly, and every one of them -- I don't 4 think we have a significant -- I don't know that I've left out 5 any side effects with significance from here except maybe 6 fatigue. Basely I've got all the significant ones and they 7 all fit the profile of a stimulant drug. That's what should 8 have been separated out. 9 If we go over here you see, well, headache. 10 Headache is often seen with stimulant drugs and in fact was 11 included in the potential syndrome by the FDA when they were 12 looking at the question of what was a syndrome being 13 proceeded. And nervousness, insomnia, drowsiness, 14 surprisingly enough does occur with stimulant drugs. It's 15 seen with amphetamines; the brain comes fighting back, 16 remember. The brain gets stimulateed, the brain fights back. 17 It's like I get drowsy at four in the afternoon because I 18 drink coffee all morning. I drink coffee all morning, and the 19 price I pay is the brain fighting back and I'm drowsy in the 20 afternoon. So it's not surprising you get some of that. 21 But the basic pattern is this. and akathisia is 22 something that after the drug is approved begins -- you'll see 23 there starts to be a lot of reports about it. 24 Q. What is that? 25 A. Akathisia is motor jitteriness kinds of 142 1 movement, the inability to stand still or sit still, 2 ants-in-your-pants kind of phenomena, got to keep moving. And 3 it's accompanied by an internal anxiety. It can vary from 4 mild, like I just don't feel right I've got to kind of move, 5 to all the way up to really driving a person to total 6 distraction in extreme cases, and has been associated with 7 violence and suicide. I'm jumping a little bit ahead. 8 Q. Is akathisia a serious condition for the 9 patient? 10 A. It can be mild to very serious. It's a major 11 reason why patients stop taking drugs. Well, akathisia was 12 not particularly noted during the clinical trials and yet some 13 studies afterwards are attributing 5, 10, 20 percent of 14 patients complaining of akathisia. It's undetermined because 15 anticipated with the condition is akathisia. It fits in. 16 In fact, it's very hard to tell a difference 17 between akathisia and agitation because agitation is defined 18 as anxiety and irritability accompanied by some display of it. 19 Agitated, you're displaying it in some way with your movement, 20 pacing. Akathisia is almost the same thing. You can try to 21 you make fine clinical distinctions, like sometimes people who 22 have akathisia have a very particular way they shuffle their 23 feet or whatever. But it's very hard to tell. You can almost 24 say that akathisia is drug-induced agitation. You can almost 25 say that; it's not quite true. 143 1 Q. Did you see any evidence of akathisia is Joseph 2 Wesbecker on Prozac? 3 A. Well, it's either akathisia or agitation, when 4 he's pacing up and down the doctor's office; when his son says 5 that he's jumpy; when he can't sleep in the same bed with his 6 ex-wife with whom he's living, with Brenda; when she says he's 7 been jittery since he got on the drug. We're looking at 8 either akathisia or agitation. For our purposes it doesn't 9 make a great deal of difference in trying to understand what 10 happened, because they're both associated with violent 11 activities, although, if anything, akathisia has been in some 12 ways more written about as producing violence and suicide. 13 At any rate, no one disagrees, I don't think any 14 of the Lilly experts that I read disagree that at least occurs 15 in a few percent of people and others think that the rates are 16 higher. I don't have a position on it. I don't think the 17 data is in yet on the difference between akathisia and 18 agitation, but I added it because it shows up in 19 postmarketing. 20 Q. But you don't have the percentages to prove it? 21 A. I don't. All of these percentages were right 22 out of these studies, but remember, again, these are studies 23 with people who don't have a tendency to be manic, studies of 24 people who aren't heavily suicidal, people getting sedating 25 drugs. So you really should imagine in that these are 144 1 actually in reality, you're higher in the normal psychiatric 2 population being given these drugs. 3 Q. Again, this is clinical trial data; this is not 4 postmarketing data. 5 A. This is, akathisia is postmarketing. Now, in 6 the clinical data, just to round it out, in the trials, it is 7 very clear that an overdose, that is extreme stimulation and 8 seizures is again part of the profile on Prozac. One percent 9 of mania, and it's important that I read to you how the final 10 conclusion that mania is much more commonly induced by Prozac 11 than by the comparitor, much more that if a person wasn't 12 manic earlier in life, then the only time that the studies 13 that he was driven to mania was by Prozac. So if you just say 14 somebody -- say I had been depressed on and off and I had been 15 treated for depression, I didn't get manic in the study from 16 any drug except Prozac. Very important. It shows the power of 17 that drug. Now, we've got reports of violence and paranoia 18 and depression and suicide, but they did not get discussed in 19 the label, and you remember my point that, in effect, suicide 20 attempts occurred at a significantly higher rate in the 21 controlled studies but did not make it into the label. 22 Q. It even occurred at a significantly higher rate 23 than items that did make it into the label? 24 A. Well, of course, a lot of items that didn't even 25 occur at a significantly elevated rate made it into the 145 1 labeling, and it certainly was occurring at a higher rate than 2 many, many of these items here. Absolutely. 3 Q. Okay. So what do we have? 4 A. We have one more step, which is to look now at 5 the postmarketing data. 6 Q. Why don't you sit down for a minute and describe 7 that information for a minute. The jury has been give some 8 information on postmarketing adverse events, SRS data. What 9 is the SRS system and the FDA postmarketing surveillance 10 purpose? 11 A. The FDA has a computerized system now called 12 MedWatch, at the time not called MedWatch, whereby anyone, but 13 they're almost all health professionals, can send in a report 14 about an adverse reaction from a drug. And the FDA encourages 15 -- very much encourages people, doctors, to send this 16 information in. 17 Q. Do they do that? 18 A. Rarely. The -- at the conference I was at just 19 this year, they reported that vast numbers of members they 20 said of industry and the academia and general practice did not 21 even know the system existed, so they couldn't be sending it 22 in. Goodman and Gillman in the classic textbook of 23 pharmacology says that up to 40 percent of physicians don't 24 know the system exists. So when you're seeing this data come 25 flooding in, it's coming flooding in from a professional that 146 1 is not particularly oriented to sending in the reports. I 2 never sent one in in my whole experience until I had one case 3 that -- 4 MR. FREEMAN: Objection, Your Honor. The 5 Witness doesn't even give medicine. 6 JUDGE POTTER: Sustained. 7 A. That's not true. 8 JUDGE POTTER: Well, Doctor... 9 Q. Go ahead and explain the system. 10 A. There's a form, and the form is sent in to the 11 FDA. The FDA then logs it and computerizes it. A lot is 12 coming in directly from health professionals, but a lot of it 13 is also coming in from the drug companies. 14 Q. How do the drug companies learn about this? 15 A. The drug companies get the information through a 16 wide variety of sources. Doctors often prefer to send the 17 information into the drug company rather than the FDA or the 18 people who are selling the drug, the drug to doctors, the drug 19 salesmen. Here's a report; they're supposed to send it in. 20 Or in the scanning of the literature that's involved that the 21 drug company does, if they come up with something, they're 22 supposed to send it in. So the drug company has its own 23 active way of developing this data. It's also getting it from 24 the public and then the FDA is getting it -- not the public, 25 but the profession, and the FDA is also getting it from the 147 1 profession and the drug company. So it's -- the FDA's system 2 includes what the drug companies are sending in. It's the 3 larger system of what's called spontaneous reports, 4 unsolicited spontaneously given reports. 5 Q. Have you seen any physician or are you aware, 6 Doctor Breggin, of the percentage of adverse events that are 7 experienced by physicians in practice that are actually 8 reported either to the drug manufacturer or to the FDA 9 directly? 10 A. I have heard estimates that the FDA estimates 11 that maybe ten percent of serious adverse reactions are sent 12 in. I've never seen it documented so I can't -- I mean, 13 everything I've given you today except that figure I have 14 documented. I've heard that figure repeated. I would guess 15 it's much smaller than that. Doctors are busy. Doctors 16 hate -- we pathologically hate paper work. Many doctors don't 17 know about the system. I think a tiny fraction of actual 18 serious reports are sent in. 19 Q. Okay. That brings me to the next question on 20 this SRS data. Much has been said that this data submitted by 21 medical doctors to the FDA either directly or via the 22 pharmaceutical companies is not causally related, in other 23 words, there's no placebo controlled double-blind trial and 24 that there may be reports of something that's not related at 25 all. What's your opinion on that as to whether or not doctors 148 1 are relating these reports in the field as being caused by the 2 drug? 3 MR. FREEMAN: Objection, Your Honor. No 4 foundation. 5 JUDGE POTTER: Sustained. 6 Q. Well, have you attended any particular seminars 7 specifically on this subject? 8 A. Yes, sir. 9 MR. FREEMAN: Objection, hearsay. 10 JUDGE POTTER: Mr. Smith, let me see you-all up 11 here a second. 12 (BENCH DISCUSSION) 13 JUDGE POTTER: Mr. Smith, where are we going? 14 MR. SMITH: Lilly has made a big deal that the 15 1639s there's been no causal relationship and that none of 16 these related to the use of the drug. Doctor Breggin has been 17 to seminars and has heard presentations made by the FDA 18 concerning the importance of the system. Doctor Breggin is a 19 practicing physician who has spent years talking with other 20 doctors in becoming knowledgeable about the SRS reporting 21 system and whether or not doctors are generally relating those 22 events to the particular drug involved. 23 JUDGE POTTER: Okay. Mr. Freeman. 24 MR. FREEMAN: First of all, it's based on 25 hearsay. He can't testify that something he heard at some 149 1 seminar led him to come to the conclusion that the FDA doesn't 2 believe that it's causally connected when their direct 3 instructions say there is no causal connection when making the 4 report. 5 MR. SMITH: That's an incorrect statement, Your 6 Honor. 7 JUDGE POTTER: What I'm ruling is, if he says 8 he's been to seminars where they tell him how to fill them 9 out, he's a doctor that hasn't filled them out. 10 MR. SMITH: He started to say, "I'll tell you 11 one" he has filled out until there was an objection. 12 MR. FREEMAN: He said he never sent one in. 13 MR. SMITH: Until he had had an adverse event 14 with Prozac. 15 JUDGE POTTER: Okay. I'm going to allow him to 16 testify what he believes the general practitioners think when 17 they should send one in. If he's been to these seminars and 18 he's part of the medical community; he can testify to that. 19 (BENCH DISCUSSION CONCLUDED) 20 Q. All right. Doctor Breggin, based upon your 21 attendance at these seminars and based on -- put on by the 22 FDA; is that right? 23 A. Yes, sir. 24 Q. And based on your medical experience, not only 25 in your own practice but in discussing these matters with 150 1 experts in the field and other physicians in the field, do you 2 have an opinion or have you come to a conclusion based on that 3 data and those seminars as to whether or not doctors are 4 indeed making some connection of the use of the drug with the 5 reaction of reporting? 6 MR. FREEMAN: Objection. This is not an opinion 7 that was ever disclosed in any of the pretrial proceedings. 8 JUDGE POTTER: Overruled. 9 A. I have an opinion, yes, very much so. 10 Q. All right. What is that? 11 A. That when a doctor takes time out from his 12 practice to write down that he's seen a drug reaction that he 13 thinks could be related, like suicide or serious depression 14 from taking a drug, that he wouldn't do that or she -- or she 15 wouldn't do that without an awful lot of conviction that it 16 was worth the time and effort of notifying a federal agency or 17 the drug company; that he would have to have a lot of sense 18 that this was an important thing to do, would not do it if 19 there was huge doubt, or at least a lot of the doctors must be 20 feeling it is a real connection if they're sending in this 21 data. 22 Q. Is it more than a smoke signal? 23 A. It's much more than a smoke signal but it's not 24 a proof. We need to look at that. It isn't a proof that a 25 lot of -- when a lot of doctors are sending in these clinical 151 1 reports, it's not a proof, but it's a lot more than a smoke 2 signal. Could I just take a couple minutes to try to explain 3 that to you? 4 Q. Please. 5 A. When there were press reports of murder and 6 suicide on Prozac, the reports from the profession, 7 spontaneous reports, also increased in number. That didn't 8 mean that there was an actual increase in what was happening 9 but, rather, that people were getting interested in the 10 problem. The doctors were seeing a problem, hearing about it 11 in the newspapers and the television, and then noticing it 12 with their patients and sending it in. So when you see, as 13 we'll see, big peaks of reports from doctors, some of them 14 coincide with either a medical report, Teischer's very famous 15 report on suicidality, or with the Wesbecker case, that was 16 also an another peak of reports. 17 Now, it doesn't mean those reports are not based 18 on anything sound; it just means that the rate of reporting 19 has a lot to do with what doctors are aware of and 20 pharmacists. A lot of these reports come from hospital 21 pharmacists, too. It just shows an increased awareness; it 22 doesn't prove causality. Causality has to come from seeing 23 the constant association being made plus does it make medical 24 sense or is there a better explanation. 25 Q. Does it make medical sense or is there a better 152 1 explanation? 2 A. I mean, that's what we're faced with. Now, in 3 fact, I mentioned to you earlier that 9 out of 15 psychiatric 4 drugs over a several-year period ended up getting much 5 stronger labels, and one was actually withdrawn from the 6 market. I've looked at those cases case by case. As far as I 7 can tell, every single decision came from spontaneous 8 reporting. 9 Now, why is that? Because these were rare 10 enough events to come up after the control trials or they just 11 got missed, and when they came up, doctors looked at it and 12 said, "Well, this is the spontaneous reporting system, but it 13 makes medical sense that the drug would do this and we don't 14 see another explanation," and that literally leads to the 15 withdrawal of drugs from the market. Most of what happens 16 after a drug is marketed in terms of changing the label and 17 withdrawing it is done on the basis of the postmarketing 18 reports of one individual case after another. 19 Q. All right. 20 A. I could give you many examples of that, but I 21 will spare that at the present time. 22 Q. Have you seen this chart before, Doctor Breggin? 23 A. Yes. That was a handout this big by the FDA at 24 the MedWatch meetings. It's in a very dramatic black. They 25 obviously wanted people, if they got nothing else from that 153 1 full day, to get the message. 2 Q. Did you write this, Doctor Breggin? 3 A. No. Obviously not. 4 Q. Is this having to do with this spontaneous 5 reporting system? 6 A. Yes. It was given out at a conference that was 7 devoted entirely to the spontaneous reporting system and it 8 was given out by the FDA. 9 Q. The FDA published this statement; is that right? 10 A. Yes. 11 Q. It says, "When a drug goes to market, we know 12 everything about its safety. Wrong." 13 A. And then it gives an 800 number, and it's an 14 urge for physicians and pharmacists and other professionals to 15 please report and to not rely on the mere fact of approval as 16 showing a drug is safe. Time and again that has shown not to 17 be the case. 18 Q. With this number you would get the FDA in 19 Washington if I call that number? 20 A. Yes. Yes, you would. 21 Q. And would I be instructed -- would they get 22 information about the particular adverse event or would they 23 send me a 1639 to fill out or do you know? 24 A. I've never called them, that number. What I do 25 know that they do do is they will -- I know they provide 154 1 forms. They'll also let you fax. My guess is they might give 2 you the fax number rather than take information on the phone, 3 but I don't know what they do. 4 Q. And it says on the bottom, "If it's serious we 5 need to know"? 6 A. Yes. 7 Q. All right. 8 A. Maybe we should jump ahead where I plan to be 9 and show what happened at the 1991 PDAC meeting. 10 MR. FREEMAN: Your Honor, it's very difficult to 11 make any sort of determination of where we're going if the 12 Witness never waits for a question. 13 JUDGE POTTER: You need to wait for a question. 14 A. Excuse me. I apologize. 15 Q. While we're on the spontaneous reporting data, 16 let me ask you if there were or if you've accumulated any 17 reports in connection with what's happened to Prozac in these 18 adverse events since 1988, when the drug's gone to market. 19 A. Well, what I had at my command was something I 20 believe that you obtained through Freedom of Information, 21 which the attorney Mr. Smith obtained the complete reporting 22 system from the FDA through -- I have it written down, 1991; 23 A. July '93, wasn't it? 24 MS. ZETTLER: Yeah. July of '93. 25 A. Very recent. July '93. And they then took that 155 1 information which was provided in a way that it could be 2 handled, computerized and provided it to me. I then took the 3 information and reorganized it. I didn't change any numbers; 4 I just put things together that belonged together so that you 5 could more easily see some of the groupings that related to 6 adverse behavioral reactions. And I asked to have a poster 7 made up, so I could show you these groupings. 8 JUDGE POTTER: We're going to need an afternoon 9 recess. Why don't we go ahead and take it now. It will be 15 10 minutes. Ladies and gentlemen, I remind you again, don't talk 11 to anybody about any topic connected with this case. Don't 12 discuss it among yourselves. We'll stand in recess for 15 13 minutes. 14 (RECESS) 15 SHERIFF CECIL: The jury is now entering. All 16 jurors are present. Court is back in session. 17 JUDGE POTTER: Please be seated. 18 Doctor, I'll remind you you're still under oath. 19 Mr. Smith. 20 MR. SMITH: Your Honor, at this time -- Exhibits 21 124 through 150 were offered and admitted into evidence 22 yesterday. We have, overnight, copied those for the jury and 23 I think it will be useful in connection with Doctor Breggin's 24 testimony. 25 MR. FREEMAN: You've already ruled on that, 156 1 Judge, but we have the same objection. 2 JUDGE POTTER: Well, they're in. 3 I tell you what, have you got that box of big 4 rubber bands? Why don't you go get them, Madame Sheriff; that 5 way you can put a rubber band around each package. 6 MR. SMITH: Maybe Ms. Putnam and Ms. Carey can 7 be rubber banding them while I proceed with the totals. 8 JUDGE POTTER: Let's just get them taken care of 9 because some jurors will be listening and some won't. They 10 can help my sheriff, I just... Give her two and then you pass 11 it out. 12 MR. SMITH: They're not collated, Your Honor. 13 JUDGE POTTER: They can take them in one of the 14 jury rooms there and collate them while you're doing that, if 15 they want to. 16 Q. All right. Doctor Breggin, previously as you've 17 discussed, we entered into evidence the numbers of adverse 18 events from the Spontaneous Reporting System through 1983. 19 And the jury will have each report through the computerized 20 summary of the data. They will have each specific one, but 21 they just have a breakdown like suicide attempt, suicide 22 attempt, suicide attempt. Would you go through these for the 23 jury and explain what we have here and what their significance 24 is, sir? 25 A. Again, this is taken from the large data base, 157 1 all the spontaneous reports that came flooding in on Prozac. 2 Prozac is the most popular psychiatric drug. It is not 3 surprising it has the most side effects being reported in the 4 record, I guess, from what I understand. But the patterns are 5 important, the particular pattern, and we could look at that 6 in different ways. 7 THE REPORTER: Excuse me. Could you please 8 speak up? 9 JUDGE POTTER: I tell you what, Mr. Smith. 10 That's plenty big enough; why don't you scoot it back some. 11 DOCTOR BREGGIN: Thank you. I don't mind at all 12 being interrupted. 13 The stimulant effect speaks for itself. I've 14 talked a lot about that. I just put together a group that 15 goes along with the stimulant continuum. The only 16 controversial cite is perhaps abnormal dreams, relatively 17 small one. I believe it's a part of insomnia and a part of 18 stimulation, so I've included it, but the others are clearly 19 stimulant agitation phenomenon. We would not expect a lot of 20 these to be reported because of the fact they're already 21 mentioned in the label. Doctors have some awareness, 22 agitation is mentioned in one place; it's just spread out. 23 It's not presented in the label as I'm presenting it as a 24 phenomena to be reckoned with in a table where you can see it 25 all, but there's one place where agitation is mentioned, and 158 1 so on. Manic reaction was mentioned and insomnia, so you 2 don't expect a lot of reports on this; nonetheless, a lot are 3 coming in. 4 Q. Well, there's a total of 4,128 reports in this 5 group? 6 A. In this group. 7 Q. If there were 10 percent only of these type of 8 reactions being reported, then would you mean maybe could we 9 say in actual practice there might have been 40,000 instances 10 where this -- 11 A. I think it's much higher than that. I don't 12 think 10 percent of these are getting reported. My guess is 13 less than 1 percent of anxiety or insomnia, hardly any 14 insomnia is getting reported. It's common with the drug. The 15 doctor wouldn't bother. 16 MR. FREEMAN: Your Honor, this is the grossest 17 kind of speculation. 18 JUDGE POTTER: Okay. Sustained. 19 Q. How about the depression and suicide totals? 20 A. Here's a pattern again, high numbers, 4,830. 21 Now, I put in depression and psychotic depression because 22 that's a part of the collection that I'm concerned about here, 23 which is the production of a worsening of depression. But 24 keep in mind, also, that when Lilly got reports of 25 suicidality, of a person feeling more suicidal from the drug, 159 1 Lilly was likely to put it under depression. So this is 2 including reports they got of people getting more suicidal, 3 people getting more suicidal are listed some under depression. 4 I wanted to show there's a significant number. It's hard to 5 judge the significance. 6 As I said earlier, many things control this flow 7 of information, but doctors are reporting aggravation 8 reactions, antisocial behavior, hostility, irritability, 9 paranoid reaction, intentional injury. Later we'll look at 10 what happens when Lilly decides to investigate whether there's 11 an increase in violence and aggression in their controlled 12 studies. When they go to investigate, they don't even pull 13 out some of these to look at, but I think this is a complex 14 issue that's all related to violence and aggression. 15 And, finally, here's duplications from the other 16 charts. I just wanted to put together the various ways in 17 which doctors are reporting and pharmacists; those are the two 18 big groups, hospital pharmacists, physicians are reporting. 19 The variety, you have, mental disturbances that could be 20 called either psychosis or severe mental dysfunction. In this 21 group, the only ones which might not necessarily be severe are 22 likely to be personality disorder or thinking abnormal or 23 depersonalization. Thinking abnormal is really not a 24 psychiatric term, it sort of means what you, think that 25 somebody decided these thoughts were abnormal but hadn't 160 1 reached some level of being psychotic. 2 Personality disorder refers to a change in self, 3 a way of relating; it's sort of lasting. It has to do with 4 kind of what your personality or character is going to be. 5 Paranoid reaction speaks for itself. It's where 6 you get distrustful and blaming and usually very angry at 7 people. 8 Depersonalization refers to a sense of not 9 knowing self anymore. I've heard many, many people say this 10 from Prozac that they'll get a -- they just don't feel like 11 they're in touch with themselves anymore, that they're not the 12 same person or they're not the person that they think they 13 are. 14 And the other thing, psychotic depression, acute 15 brain syndrome. Acute brain syndrome is a very serious 16 phenomena. That means your brain is now in a delirious state. 17 You're confused, puzzled, can't think straight. You're 18 disoriented, your judgment or your emotions are out of whack. 19 That's an acute brain syndrome. Confusion is an aspect of 20 acute brain syndrome. 21 Delirium is almost synonymous. Nowadays they 22 tend to be used synonymous, delirium and acute brain syndrome. 23 Delusion, where he imagines remembering being forced to 24 perform humiliating sexual acts in front of other men by his 25 supervisor, an extremely unlikely event; saying he reported 161 1 it, in fact, to some agency, telling it to the doctor on his 2 last visit to Doctor Coleman almost surely as indeed one of 3 the -- at least one of the experts with Lilly has said almost 4 surely a delusion. Manic depressive reaction and manic 5 reaction, psychosis, schizophrenic reaction and so on. 6 Now, I won't put much stock in a report of 16 or 7 4, but when you begin to see these patterns, they are -- they 8 are powerful signals, and what the doctor has to ask is, given 9 the signal, does it make sense. Is there other evidence to be 10 brought to bear on that. Now, one of the big questions is 11 would other drugs show up with, say, the same amount of 12 violence and aggression proportionately so if you take a drug 13 that's only a tenth as popular as Prozac, if you take that 14 drug, would it show up proportionately to be doing the same 15 amount of violence. So let's say, in other words, if you got 16 ten acts of violence on Prozac and only one on Trazodone but 17 Prozac was ten times more popular you'd say, well, they're 18 both doing it or maybe they're neither doing it. It doesn't 19 tell us exactly what's going on. There's no difference 20 between the drugs. 21 Q. We have some charts on comparisons with Prozac 22 and Trazodone. Would it be helpful now to explain those? 23 A. This material has an interesting history for me. 24 JUDGE POTTER: Doctor, why don't you wait for a 25 question. 162 1 MR. SMITH: Could we maybe pass those out while 2 we're getting the next chart, Your Honor? 3 SHERIFF CECIL: There's 15. 4 JUDGE POTTER: Is that an extra one there on the 5 table? 6 Doctor, I'm going to ask you if you and Mr. 7 Smith will change places, and that way my Court Reporter will 8 be able to hear you better. 9 Q. Okay. Now, I believe this is already in 10 evidence, Doctor Breggin, as plaintiffs' exhibit -- it's 11 already in evidence. I know that. This compares hostility 12 and intentional injury, two factors that might be considered. 13 Is that all the factors that might be considered in whether or 14 not Prozac is producing violent-aggressive behavior? 15 A. As I mentioned earlier, there's many factors 16 that would go into it, but there is certainly a huge signal 17 given that Prozac is a very popular drug, it certainly isn't 18 proportionately and I'd have to go and look at the data, but 19 it's not proportionately that much more popular when you add 20 up figures for the most popular drug prior to Prozac, for 21 example. 22 Q. Well, also, Doctor Breggin, this chart takes 23 into account 1982 until 1991. We know that Prozac didn't come 24 on the market until 1988, and that these other antidepressants 25 were on the market for five years or six years before Prozac 163 1 and, in effect, had a six-year medical start in reporting it. 2 Would that be correct? 3 A. Yeah. There's no doubt for whatever reason that 4 hostility, intentional injury is being disproportionately 5 reported with Prozac. I think these figures make that 6 100-percent clear. The question, though, is, well, could that 7 just be publicity. Could that just be that there have been so 8 many reports in the press that doctors and pharmacists are 9 being influenced. Now, remember, the people who we're talking 10 about being influenced are not nonprofessionals. The doctors 11 may be seeing the media, but are they being nonetheless 12 influenced to suddenly say something which occurred all along 13 with all those other drugs and is now occurring on Prozac and 14 they're just now reporting it. 15 Q. What's your opinion on that, Doctor? 16 A. I don't think so. Nor do I think the doctor 17 would be imagining the phenomena because they've heard it in 18 the media nor in the reports, because there are many reports 19 on particularly suicide in the medical literature and in the 20 media of the violence. So it's hard to imagine hospital 21 pharmacsts and physicians being so motivated to produce this 22 distorted picture. 23 We can, however, focus in on the question in 24 another way, which is to look at the time line of reports of 25 hostility and intentional injury before it became a national 164 1 issue and to compare it actual percentagewise of prescriptions 2 to the other drugs. Let me show you that. Should I mention 3 the numbers so that they're on the record? 4 Q. They're in evidence in Plaintiffs' Exhibit 120. 5 Is this the chart you want? 6 A. Yes. 7 Q. All right. Now, come over here, Doctor Breggin, 8 on the other side so that the Court Reporter can hear you. 9 This appears to be in reports per million, so we've got the 10 disparity of popularity of the drugs accounted for; is that 11 correct? 12 A. Yeah. Well, let me explain where this data is 13 from. 14 Q. Okay. 15 A. In 1991, there was a hearing held on this by the 16 FDA, and when I read the transcript of the hearing I noticed 17 something which was very surprising to me which wasn't paid 18 attention to, which was that the physician in charge of 19 collecting the data -- this data is collected by the FDA and 20 analyzed by the FDA; that he had said that, in fact, violence 21 was disproportionately represented even taking into account 22 the popularity of Prozac. And I read through this transcript 23 and I waited for others to pick up on it and I couldn't. I 24 called the doctor in charge of this program and asked if I 25 could get ahold of his data and I couldn't, and so I did a 165 1 Freedom of Information Act and they still wouldn't produce 2 their data. 3 MR. FREEMAN: The transcript itself would be the 4 highest and best evidence, and to try to characterize it is 5 not a proper way to go about it. 6 JUDGE POTTER: I think how he comes to where he 7 is is probably not very important. He needs to deal with the 8 question. 9 A. This was produced through Eli Lilly through the 10 request for information by the attorneys. This is the chart 11 that I was looking for from the FDA, and what we see here is a 12 comparison between fluoxetine and Trazodone. They picked 13 Trazodone because it's relatively newly approved during the 14 period when the system is working about as smoothly as it is 15 now. It's not a very old drug and it is an antidepressant. 16 And you'll notice the comparison is per prescription. So, in 17 other words, this is taking into account that Prozac 18 prescriptions are written as a much higher rate than 19 Trazodone. It's taking that into account and then showing 20 you, given that Prozac is used much more and prescribed much 21 more, what's the proportion of reports we're getting. 22 Q. Of course, there's none from 1982 to 1987 23 because Prozac is not on the market; correct? 24 A. Yes. Now, we start here and we see a little 25 tiny blip of reports in the first year. 166 1 Q. That would be Trazodone, wouldn't it? 2 A. In Trazodone, not uncommon. First year of a 3 drug is when doctors get interested and think something's new 4 and they're going to send reports. It's a well-known fact 5 that in the beginning, the first year or two, is when you get 6 most of your spontaneous reports. By the time it's been out 7 two or three years, it's proportionately quite low. The first 8 year, 1988, of Prozac before there's any publicity shows a 9 proportionately high rate of reporting. 10 Q. All right. Go ahead. 11 A. 1989, still very high proportion. I didn't 12 measure this out. It's -- it looks like about four to 13 one-half, maybe eight to one more reports based on taking into 14 account that the drug is being used more. 15 Q. And it's equalized because it's reports per 16 million? 17 A. Per million prescriptions. And we get to 1990 18 and we see a jump, and that's probably because we're seeing 19 the results along the way of what happened with Mr. Wesbecker 20 and other reports in the media. There were dozens and dozens 21 of reports in the media of violence from Prozac. Then in 22 1991, a paper is published on suicide, not on violence, on 23 suicide, that draws people's attention, and notice the 24 violence reports are going up, violence and intentional 25 injury. Some of this is definitely the product of media 167 1 attention, but it doesn't mean it's wrong. 2 Q. Okay. What do you mean by that? Let's analyze 3 that. Because Lilly said the only reason you're getting any 4 reports of hostility, intentional injury or suicide is because 5 all this publicity. 6 A. Well, clearly it's not there in 1988. 7 Q. All right. What was what, eight to one? 8 A. Oh, at least. Yeah. Oh, gosh, it could be much 9 more than eight to one. Do we have that as a number? I don't 10 know. But, anyway, you can see it; it's very visual. And in 11 '89 it's also very high, again not accountable strictly by the 12 media at all. 13 Now, in 1990 when the burst comes, we could say, 14 okay, the reason you get a burst is that people are paying 15 more attention to the issue. But, nonetheless, it doesn't 16 mean that the doctors and the pharmacists are making up the 17 connection, it just means they're reporting more; they're 18 seeing it more; they're taking it more seriously. But I think 19 that the really important -- most important point here is the 20 fact that, A, this happens before there is media attention at 21 all to this issue and, B, it happens at a much higher rate 22 than to be expected merely from the fact this drug is 23 prescribed more often. 24 Q. Well, would you expect to see, even though 25 Prozac was the center of controversy, more doctors were 168 1 becoming more attuned to hostility and violence in connection 2 with antidepressant treatment, that they would be reporting 3 similar acts of hostility and violence with any antidepressant 4 treatment, including Trazodone which is mentioned here? 5 A. Certainly I looked for that and I have looked 6 for that in data, but also when I've traveled I've waited for 7 the reports to start coming in from Elavil or Tofranil or 8 other antidepressants and they aren't coming in the 9 literature, they aren't coming in in this spontaneous 10 reporting system. 11 MR. FREEMAN: Your Honor, this is again very 12 much conclusionary, not based on any scientific evidence at 13 all. 14 JUDGE POTTER: Sustained. He can cite his 15 sources. 16 A. Well, we have a source. 17 Q. Just confine yourself to this chart alone. 18 A. The chart confirms there's no piggybacking of 19 Trazodone. It's not like people are now noticing, hey, 20 Trazodone is doing it, too. They are not doing that 21 reporting; what's going up is the Prozac. 22 Q. All right. 23 A. May I sit down? 24 Q. Sure. 25 All right, Doctor Breggin. It appears that you 169 1 have pretty well in depth reviewed with us the animal studies, 2 the early Phase 1 studies, and the Lilly clinical trials in 3 connection with the stimulant agitation nervousness profile 4 and in connection with the profile of increased suicidality 5 and increased incidence of violent and aggressive behavior and 6 followed that up with the postmarketing data that I would 7 assume you conclude supports what was seen in the clinical 8 trials? 9 A. Yes. Very, very much so. 10 Q. Now, is there any specific literature in 11 connection with whether or not other than what we've seen 12 already in the animal studies reported of violent, you know, 13 cats growling and hissing, people becoming hostile, is there 14 any other literature linking Prozac or the reuptake of 15 serotonin to violent-aggressive behavior? 16 A. I made a little summary card to spare you the 17 big cards and just to go over briefly, but I'm having a little 18 trouble locating it. Basically let me just say without going 19 into detail that there are many reports in the literature on 20 suicide in association with Prozac; the first of the big ones 21 was in 1990. 22 MR. FREEMAN: The answer is not responsive to 23 the question. The question was about violent and aggressive 24 behavior, as I listened to it. 25 Q. That's what he's answering, Your Honor. 170 1 JUDGE POTTER: Objection is overruled. 2 A. We'll start with the suicidal aspect of violence 3 and then I'll go to the literature on externally directed 4 violence. We have both in this case, obviously. Teischer 5 reported on six patients -- he's a Harvard professor -- and he 6 was reporting with Jonathan Coale, who has been an 7 investigator with Lilly; two very, very respected 8 psychiatrists. Coale is the kind of person who's always 9 getting packed houses at the national psychiatric meetings on 10 pharmacology, very prestigious, Jonathan Coale, older man, 11 Harvard. And they reported that six patients of theirs got 12 compulsively suicidal in a way that had never been seen before 13 on Prozac. 14 This is complicated. Many of the patients had 15 other drugs, not all of them. The patients had been somewhat 16 suicidal before, but they saw this as a very important 17 significant phenomena, compulsive suicidality, and it was 18 published in the American Journal of Psychiatry, the official 19 journal of the American Psychiatric Association. Doctor 20 Teischer also reported that a Barbara Geller, a psychiatrist 21 from South Carolina, whom he said had some other cases which 22 involved both violence and suicid -- 23 MR. FREEMAN: Your Honor, may I approach the 24 bench, please? 25 JUDGE POTTER: Okay. 171 1 (BENCH DISCUSSION) 2 MR. FREEMAN: The Doctor is attempting to 3 regurgitate the contents of the report, which is not 4 accurately done in many cases, particularly with respect to 5 compulsive suicidality and characterizations like that that 6 are not either contained in the reports or otherwise. We 7 object to him continuing to regurgitate what things are 8 reported to say, rather than going to the highest and best 9 evidence, which is the articles themselves. 10 JUDGE POTTER: Mr. Smith. 11 MR. SMITH: He's quoting from the articles. 12 He's quoting to the articles. He is an expert giving the 13 summary of the scientific literature in connection with Prozac 14 and suicide and violent-aggressive behavior. Obviously, if 15 you want to cross-examine him about each and every item, 16 that's something you can do, but I don't have to have him read 17 each and every report. 18 JUDGE POTTER: I don't think he's quoting from 19 them; he's summarizing them. How many of these things have 20 you got, Mr. Smith? 21 MR. SMITH: Half a dozen is all. It's not going 22 to take two more minutes, I don't think. 23 JUDGE POTTER: And they're all things that are 24 available for these people on cross-examination? 25 MR. SMITH: Absolutely. 172 1 JUDGE POTTER: If he wants to summarize the 2 articles that he's relied on, I'm going to allow him to do it. 3 (BENCH DISCUSSION CONCLUDED) 4 Q. Go ahead in your summary of the articles linking 5 Prozac to either suicidality or violent-aggressive behavior, 6 Doctor Breggin. 7 A. Doctor Geller's observations according to Doctor 8 Teischer were very important and occurred during a clinical 9 study. 10 Q. A Prozac clinical study? 11 A. A Prozac clinical study. Doctor Geller then 12 wrote to the American Journal of Psychiatry in seeming 13 criticism of Doctor Steiner saying that Doctor Teischer was 14 mistaken, these had not occurred in a clinical study, and she 15 said his work was nonetheless worth supporting; very, very 16 short. Through Lilly we were able to obtain -- Mr. Smith was 17 able to obtain the original letter from Geller to the American 18 Journal of Psychiatry, which was also shared with Lilly before 19 publication, apparently, which is stripped -- the original 20 letter has all this clinical data which just never gets 21 published and here's some of the data; it's extremely 22 pertinent to this case so I will again go to the card. This 23 is a letter on January 19th, 1991, for publication to the 24 American Journal of Psychiatry by a team involving Doctor 25 Geller and two other people. And in it they give the data 173 1 that Doctor Teischer was talking about that never made it into 2 print. 3 A 13-year-old man, boy, was given 20 milligrams 4 of Prozac, seemed to improve, and in a month, one month, same 5 general period as Mr. Wesbecker, became irritable and angry. 6 The school could no longer handle him due to, quote, increased 7 agitation which appeared to the parents and the school to be 8 substantially worse than they noted at prior times. He then 9 recovered well without Prozac. 10 Case Number Two: It's a 13-year-old male again 11 on Prozac and lithium -- so again we have a comparison to Mr. 12 Wesbecker -- for nine months. Quote, became more markedly 13 agitated than he had previously been and was verbally 14 threatening to kill everyone in sight. Here's a boy suddenly 15 threatening to kill everyone in sight. Quote, he recovered 16 from the extreme agitation after fluoxetine was discontinued 17 and while continuing to receive lithium. This seems, although 18 it's months later, very close to the kind of phenomena with 19 Mr. Wesbecker, although this is a child and Mr. Wesbecker 20 obviously acts upon this wish to kill everyone around him, it 21 seems. 22 Another case, and that's a 17-year-old, a 23 female, after she had received fluoxetine for six months she 24 developed severe acute suicidal ideation that was worse than 25 she had ever experienced in any prior time. The symptoms went 174 1 away when Prozac was stopped and then, interestingly enough, 2 they tried Prozac three months later and in this case they 3 didn't come back. We'll see some other cases where they come 4 back. 5 Another, a fourth case on lithium and Prozac 6 that initially helped her feel better -- again, Mr. Wesbecker 7 thought it was helping him -- and she on 40 milligrams 8 developed severe and persistent suicidal ideation and behavior 9 described as more suicidal than she had ever been. Lithium 10 was increased. 11 JUDGE POTTER: Mr. Smith, let me see you up 12 here, please. 13 (BENCH DISCUSSION) 14 MR. SMITH: I'm sorry. I didn't know he was 15 going to go into detail. 16 JUDGE POTTER: If he wants to tell an article 17 and cite if Doctor Smith in his article said in his article 18 thus and so, but now he's reading anecdotal reports. Maybe my 19 ruling wasn't clear. 20 MR. SMITH: He's reading from the article. 21 JUDGE POTTER: As I understand he's reading some 22 letter that he found in his files. 23 MR. SMITH: Okay. But he was -- all right. 24 JUDGE POTTER: And if he wants to, you know, 25 there's no point in reading all these anecdotal things. If he 175 1 wants to say the Doctor believed that it was connected and 2 then go on... 3 (BENCH DISCUSSION CONCLUDED) 4 Q. Doctor Breggin, as I understand it, those 5 anecdotal reports were reported by Doctor Geller in a letter? 6 A. The team of Doctor Geller; two other doctors, 7 too. 8 Q. In a letter to the American Psychiatric 9 Association or was it to Lilly? 10 A. This is to the American Psychiatric Association 11 for publication in the journal; however, it was obtained by 12 Lilly according to the markings on the document seemingly 13 before it was published and it was published without any of 14 the data. 15 Q. All right. That's then -- since it was not 16 published with that data, just -- let's go on to the next 17 article that was actually published leading to or supporting 18 the conclusion of violence or suicidality being associated 19 with Prozac. 20 A. Okay. And I'm going to go a little faster now, 21 I'm hoping the pattern is clear. Doctors King and Riddle and 22 others from Yale, as I recall, published a paper in a major 23 academic journal on the emergence of several destructive 24 phenomena in children and adolescence during fluoxetine 25 trials. Six of forty-two children in one of their studies 176 1 developed self-destructive and agitated phenomena. 2 In a retrospective study, it was found that 3 fluoxetine produced more suicidal behavior than another 4 antidepressant and this study came out of Taiwan. 5 Q. All right. What was the -- do you have the 6 numbers of the individuals who attempted or committed suicide 7 in that study on Prozac versus the other antidepressant? 8 MR. FREEMAN: This is another nonpublished 9 article, Your Honor. 10 A. Some of this was published. 11 JUDGE POTTER: I'm sorry. Doctor, is that a 12 published article? 13 A. I have the information from two sources. One 14 seems to be a published abstract that looks like a publication 15 in an abstract, and the other information is from an FDA 16 report, as well. But this information I'm giving you is an 17 abstract and it looks published to me. 18 JUDGE POTTER: Objection is overruled. 19 Q. What were the numbers on that? 20 A. Of completers, people who finished the studies, 21 and this is retrospective looking at them, of 46 fluoxetine 22 completers, a little more than 15 percent developed suicide -- 23 made suicide attempts. Fifteen percent made suicide attempts 24 and zero of thirty maprotiline, another antidepressant, zero 25 in that group, and this was thought to be statistically 177 1 significant. 2 In a very interesting study in the Journal of 3 Analytic Toxicology, two toxicologists working in a coroner's 4 office in Texas, I believe, attempted to notice that they 5 thought they were getting a disproportionate number of 6 completed suicides on Prozac and they wrote, "Recently, case 7 reports have suggested that it may produce suicidal tendencies 8 in some patients." Recently, however, they say, "The report 9 provides data from a medical examiner regarding a number of 10 cases in which fluoxetine has been depicted and the 11 proportions certified as suicides." And then later they say, 12 "This data shows that suicide occurs in a significant 13 proportion of people who are while taking antidepressant -- 14 you have people who are taking antidepressant drugs; however, 15 it is apparent that the proportion taking fluoxetine -- it is 16 apparent that the proportion taking fluoxetine is higher by an 17 amount to be of concern to medical examiners and also to 18 health-care givers." And it concludes, "All physicians who 19 consider utilization of fluoxetine for their patients must be 20 knowledgeable about this possible association and alerted to 21 possible adverse effects in their patients." 22 Q. Where was that study published? 23 A. The Journal of Analytic Toxicology, 24 March/April 1992. They had 15 cases. 25 You see, this is hard for people to figure out 178 1 how to measure this so people are trying indirect ways. And 2 another interesting method was by a Seymour Fischer, and 3 Bryant and another group of people, physicians and 4 pharmacologists, in the Journal of Clinical Psychology in '93. 5 And what they did was to give patients at the pharmacy the 6 opportunity to call in -- I believe it was call in side 7 effects of drugs. Say, here, do this research project. So 8 it's controlled. They're giving it to patients taking 9 fluoxetine and patients taking, as I recall, Trazodone, and I 10 have a very skimpy summary here of Trazodone. And what they 11 concluded was that data are presented indicating a higher 12 incidence of various psychological and psychiatric adverse 13 clinical events, including delusions and hallucinations, 14 aggression and suicidal ideation. 15 In addition, I have a stack of individual 16 clinical reports. There are many in the literature on suicide 17 associated with the drug. 18 Q. When you say individual clinical reports, would 19 that be where a doctor wrote to a particular medical journal, 20 the Journal of the American Medical Association, New England 21 Journal of Medicine, and just did a letter to that journal 22 which was published describing a particular event in 23 connection with Prozac? 24 A. Well, they're not just letters. They're reports 25 and in some cases just extrapolating information out. You 179 1 have a report which was not intended for that purpose going 2 back and noticing, look at this control trial. We've got a 3 number of suicides or suicidal attempts, it was overlooked, 4 and then going back and finding that data, so it was a variety 5 of different things. 6 Q. All right. Let's don't go through each one of 7 those individually. 8 A. No. We'll skip them. 9 Q. But have you got any count on how many there 10 would be? Is it more than a dozen? 11 A. It's probably in that range. 12 Q. All right. Next, do you have another category 13 of scientific literature or documentation in addition to the 14 Lilly animal studies, in addition to the Lilly clinical 15 trials, in addition to the postmarketing experience describing 16 this phenomenon of Prozac and its connection with 17 violent-aggressive behavior? 18 A. Yes. One of the phenonema that I mentioned to 19 you earlier that didn't come up in the original trials very 20 much but which later has become a major issue, is akathisia 21 produced by Prozac. Now, akathisia, remember, is a phenomena 22 of an inner irritability which can progress to a terrible 23 inner torture. Quite literally, you feel like you're being 24 tortured inside out with a driveness to move about. You have 25 to get out of your seat and have to move about. This is a 180 1 very, very well-documented phenomena. It has been known 2 clinically for some time that akathisia can produce dysphoria, 3 that is, emotional pain, irritability, aggression and suicide. 4 It is so generally accepted that it's listed in the DSM-IV, 5 the Diagnostic and Statistical Manual, the American 6 Psychiatric Association, conservative kind of a document. It 7 mentioned association of akathisia with aggression and 8 suicide. People feel driven to something drastic. 9 Now, as I mentioned, there's no way to really 10 know just what do you call what Mr. Wesbecker was going 11 through, akathisia or agitation. There's general agreement in 12 at least two of the Lilly experts that akathisia can cause 13 abnormal behavior. First Doctor -- we mentioned Doctor Schwab 14 who is one of the experts, and he -- he himself, unlike the 15 other two experts for Lilly, doesn't believe that akathisia 16 causes violence and suicide. He doesn't agree with that part. 17 The other two Lilly experts do, but he does agree that it's 18 one of the phenomena you can see with Prozac. He likes to 19 start at 10 milligrams with patients and he based this on the 20 level that he sees of anxiety, irritability, motor 21 restlessness. He likes to start with lower doses if he sees 22 this phenomena, he's heard this discussed, he said in his 23 depo, at medical meetings of scientists. He says he teaches 24 this. He thinks that akathisia with Prozac is pretty rare, 25 though. So he's more talking about agitation. 181 1 Now, we have many reports now of fluoxetine- 2 induced akathisia. This is a recognized clinical entity. And 3 in a very interesting study in 1991, Rothschild and Locke, 4 both physicians, found three patients who had become acutely 5 compulsively unexpectedly suicidal in association with 6 akathisia. And they retried them on Prozac and they concluded 7 that this was -- that patients had been reassimilated through 8 severe compulsive suicidality by akathisia from Prozac. And 9 they say the akathisia and suicidal thinking abated on the 10 discontinuation of the fluoxetine or on the addition of 11 Propanolol, which is something that eases akathisia. So they 12 either stopped the drug and the upset stopped or they gave a 13 drug to help with this problem. 14 The cases are -- they're really gripping. I 15 mean, these people were driven out of the blue, in a sense. 16 Q. Well, let's not describe each individual case. 17 A. No. I'm going to another card, mercifully. I'm 18 going to another card. William Wershing and Van Putten is a 19 person I've admired for years and his abilities to observe 20 patients, and they added five patients to what they thought 21 was the growing literature of people who at, quote, a peak of 22 their restless agitation developed serious suicidal impulses. 23 Q. On Prozac? 24 A. On Prozac. 25 Q. All of these people are on Prozac? 182 1 A. Yes. 2 Q. All right. 3 A. Now, they made an interesting point and Teischer 4 has made an interesting point and as I finish this section I 5 want to take a minute with this, and that is that the fact 6 that you don't necessarily see a lot of this in a controlled 7 study, the smaller controlled studies doesn't prove a lot, 8 because it's assumed that some people are getting better from 9 the Prozac. So if some people -- 10 MR. FREEMAN: I may be missing something, but I 11 don't think this is in response to any question. 12 JUDGE POTTER: Doctor, I think you do need to 13 wait for questions. 14 Go ahead, Mr. Smith. 15 Q. In some studies that are small, you will see 16 that some people are getting better and that there may be no 17 association of suicidality in those particular studies. Is 18 there an explanation for that, Doctor Breggin? 19 A. Yes. This has happened in a number of studies, 20 the rate of suicidal activity either stays the same or, as we 21 saw, goes up. How can you explain that when the group is 22 getting less depressed? Think about this. 23 Q. Wait a second. I don't follow that. 24 A. All right. You have a study and you look at the 25 end point of the study and a lot of patients are feeling 183 1 better, somewhat better, the drug is helping people be less 2 depressed, yet the rate of suicidality is the same. How do 3 you explain that? Why if people are getting better is the 4 rate of suicidality remaining the same? We saw it actually go 5 up in terms of one of the main studies done by the overview, 6 but in a lot of studies it stays the same. The only way that 7 the doctors could think of that a rate of suicidality would 8 remain the same, which is the common finding, while people are 9 getting better is if new people are being made suicidal 10 because, after all, a lot of people are getting better, so why 11 is the suicidality remaining steady. 12 Q. So you're saying that if the drug is indeed 13 reducing or not causing suicidality, you should be seeing a 14 diminution of that? 15 A. Nicely put, sir. The suicidality should be 16 going down as the depressive symptoms go down, yet the studies 17 show -- studies out of England by Montgomery and in general 18 that Prozac does not reduce suicidality, it may even increase 19 it, as we've heard from several sources, and as proven by the 20 one study showed. How can that be? It must be that the 21 situation is much worse than it even looks because, clearly, a 22 lot of patients are getting better and yet the suicidality 23 remains. Those are probably new patients. 24 So on the one hand, some people are feeling 25 better; on the other hand, people are getting more suicidal. 184 1 It's confusing. I had to read it ten times to get it in two 2 different studies. 3 Q. What is the last piece, Doctor Breggin? 4 A. And that is the degree to which others have come 5 to the conclusions I'm suggesting to you, which is that this 6 drug can promote suicidality. Two of Lilly's experts suggest 7 this conclusion indirectly. Let me -- not very complicated. 8 Doctor Granacher said clearly that Prozac can cause akathisia. 9 He then said that akathisia causes aggression and suicidality; 10 he just didn't think it happened in Mr. Wesbecker's case. 11 MR. FREEMAN: We object to that on the grounds 12 it's not what Doctor Granacher said at all; it's a total 13 mischaracterization. 14 JUDGE POTTER: Mr. Smith, Lilly's experts are 15 going to testify here; they'll speak for themselves. I think 16 the Doctor should rely on something other than paraphrasing 17 their anticipated testimony. 18 Q. All right. 19 A. Doctor Teischer and Doctor Coale came to the 20 conclusion that Prozac could cause suicide and they gave a lot 21 of different approaches and explanations to the problem. Two 22 colleagues of mine from where I was trained part of the 23 time -- I didn't know them because this is recent, but Kwan 24 and Massan wrote that, "We conclude from these 15 cases that 25 Prozac can cause suicide ideation in some patients." They 185 1 just flat-out concluded. "And given these currently available 2 facts, we suggest the following guidelines for physicians." 3 And I'll just give you their fourth and fifth guideline: 4 "Educate and monitor patients for akathisia since it may lead 5 to suicidality in some patients. Five: Clearly inform" -- 6 this is very important -- it's very important about the label 7 for Prozac, so I want you to really listen to this. These 8 doctors are saying clearly inform all patients of the very 9 real but small risk of treatment-emergent suicidality whether 10 they are being treated with Prozac or another antidepressant, 11 although this is all about Prozac. Emphasize that 12 discontinuation of the drug if suicidal ideation does occur 13 has led to quick and complete remission in every reported 14 case. 15 Lancit. Lancit is perhaps the most prestigious 16 medical journal in the world, maybe the New England Journal of 17 Medicine would argue about it. In an editorial in 18 August 11th, 1990, it said flat out that fluoxetine side 19 effects include, quote, the promotion of suicidal thoughts and 20 behavior. No equivocating about it. Lancit editorial said it 21 outright; other doctors have said the same thing. The French 22 in fact require it to be included in their label as a direct 23 statement, and the FDA continues to worry about the problem as 24 late as 1992, which is my last information, because they keep 25 getting reports of increasing reports of suicide attempts, 186 1 overdose, hostility and unintended pregnancy. This is what 2 they say. Several events have been reported with a relatively 3 greater frequency in 19 spontaneous event reports than were 4 reported in 1990 and they include these items, and someone 5 asked me how would you include unintended pregnancy with 6 suicide attempt, overdose and hostility. Remember, it's loss 7 of impulse control that is due to the effects of this system, 8 and certainly this could be a measure of that. 9 Q. All right. So what is your conclusion, Doctor 10 Breggin, from your review of the scientific literature, from 11 your review of the Lilly human and animal clinical trial data 12 and your review of the spontaneous reporting system 13 information in connection with whether or not Prozac does 14 cause individuals to become violent or aggressive? 15 A. Well, first, I finished -- I have a little more 16 really -- I have some significantly more on violence and I'd 17 like to finish that. My conclusion is that it does indeed 18 cause violence and suicide. I want to focus just a little bit 19 more on violence, per se, by itself, although you can see how 20 it gets mixed in with the other studies. 21 Q. All right. Is this a review of the scientific 22 literature, then? 23 A. Yes. 24 Q. Having to do with violence? 25 A. Yes. 187 1 Q. And its relationship to the use of Prozac? 2 A. Yes. 3 Q. All right. Let's go through that, then. 4 A. We've already done some of that along the way 5 with akathisia and so on, but this has become such a 6 recognized issue now that the Textbook of Neuropsychiatry, 7 Second Edition, 1992, produced by the American Psychiatric 8 Association's president speaks at length of how anxiety and 9 tension due to neuropsychiatric disorders, and they're 10 including here drug toxicity can produce a wide -- 11 MR. FREEMAN: Your Honor, that's a 12 mischaracterization, just these anecdotal things which he says 13 they intend to include when they don't. 14 JUDGE POTTER: Let me see you-all up here for a 15 second. 16 (BENCH DISCUSSION) 17 MR. SMITH: It's in scientific literature that's 18 available. 19 JUDGE POTTER: He's got copies of everything? 20 MR. SMITH: He produced a file drawer full of 21 material for them at their deposition on this. 22 JUDGE POTTER: I'm going to overrule the 23 objection because I assume we're getting close. I'm going to 24 overrule the objection, but before you go forward you ask him 25 if he's got with him copies of everything he's referring to 188 1 because I want them to have it tonight so they can 2 cross-examine him. 3 MR. SMITH: Neither one of you was there when 4 the deposition was taken. 5 JUDGE POTTER: Just ask him to make sure that he 6 has that with him and we may take it up if it wasn't produced, 7 but he's got to have it with him. 8 (BENCH DISCUSSION CONCLUDED) 9 Q. Doctor Breggin, do you have these scientific 10 journals and textbooks with you that you're quoting from? 11 A. I have this chapter, yes, with me. 12 Q. All right. Did you in fact produce this to the 13 Lilly lawyers when they took your deposition in Bethesda, 14 Maryland, a couple of months ago? 15 A. I'm not sure I produced this one. I'm not sure 16 I produced this one. I gave them several cartons of material. 17 I cannot say with certainty I produced this particular 18 document. I know I produced a lot of book chapters and I know 19 they didn't reproduce them or copy them, but I just can't say 20 with certainty. 21 Q. Well, do you have that particular chapter? Did 22 you bring it with you to Louisville? 23 A. Yes, sir. 24 Q. So we can show it to them if they need to see 25 it? 189 1 A. Sure. 2 Q. All right. What's the next? Or did we cover 3 the substance -- 4 A. No. They go on to specifically link this to 5 Prozac. 6 Q. What do they say? 7 A. They specifically go on to say that -- they say 8 their issue -- they're talking about the impulsive behavior 9 produced by neuropsychiatric disorders that are caused by 10 drugs, and they talk about, quote, a hyperaroused state with 11 an increase in impulsive behavior. That's exactly what I've 12 been talking to you about in such detail today, a hyperarousal 13 state with increase in impulsive behavior. This is a 14 continuous quote now. "This issue has recently been raised in 15 connection with suicidal or violent behavior in patients 16 initiating therapy with fluoxetine, but hyperarousal can be 17 seen with any of the antidepressants. It is perhaps less 18 common with the more sedating agents such as Trazodone and 19 amitriptyline." 20 Q. Any other scientific literature, Doctor Breggin, 21 that you've either produced or that you have here available 22 for the defendants to review confirming the scientific opinion 23 that Prozac is indeed related to have a homicidal behavior? 24 A. In one of the studies I mentioned under suicide, 25 King, three of the patients -- 190 1 MR. FREEMAN: Did we get the answer to did he 2 produce it or does he have it available? 3 JUDGE POTTER: Why don't you get him straight on 4 what he produced for them before on each of these. 5 Q. Okay. In your deposition -- I understand that 6 you produced cartons and cartons and documents for the Lilly 7 lawyers when your deposition was there. I was there; you were 8 there. Right? 9 A. Right. 10 Q. Do you remember whether this particular article 11 was in one of the cartons that you produced? 12 A. No, but I remember it was listed for them as 13 something I was going to rely on. I remember that about King. 14 I think we can find that on an exhibit from the depo. Should 15 I try to find that? 16 Q. Well, did you specifically mention this same 17 article in testifying in your deposition? 18 A. Yeah. Well, either I mentioned it specifically 19 or it's in the notes that I gave them, which are printed out 20 as to some of the things I was going to use. I mentioned the 21 King article, the Teischer article. 22 JUDGE POTTER: Go ahead, Mr. Smith. 23 Q. Describe that. 24 A. Well, one patient developed -- I may have 25 mentioned it -- violent nightmares about killing classmates. 191 1 Another patient, a young woman, stamped on her teddy bear 2 yelling "Kill, kill, kill." They felt this was concerning 3 Prozac. 4 Q. I want the name of the publication. 5 A. King's publication. Well-known publication. 6 And then Teischer in '93. 7 Q. Is this another Teischer article? 8 A. Yeah. Later he talks about a person who was 9 consumed with stabbing her father to death, didn't do it, on 10 the drug. I've mentioned a number -- I won't repeat it -- 11 whenever I was going through it originally. 12 Now, Lilly itself did a study of suicide. 13 MR. FREEMAN: There's not a question being 14 asked. 15 JUDGE POTTER: Mr. Smith, why don't you ask him 16 a question so he can answer it. 17 Q. Any other scientific data supporting the 18 conclusion that Prozac causes violent-aggressive behavior? 19 A. Excuse me. I mentioned earlier the Fischer and 20 Bryant study on the patients who were asked to produce data at 21 the pharmacies, that showed increased -- 22 Q. In addition to increased suicidality? 23 A. Yes. Showed increased aggression. Most of this 24 now, I'm just summarizing things we talked about before. We 25 looked at the charts produced by the FDA, and one of the 192 1 Doctor Fevey, one of the clinical investigators for Prozac, 2 has written that Prozac in a high percentage of patients, two 3 or three percent in his experience manic behavior with 4 paranoia, clearly a dangerous situation. I think we could at 5 this point, you know, stop with this because I'm sort of 6 trying to summarize and organize but... But I pretty much 7 covered a lot of what I wanted to cover. 8 Q. All right. Anything else before we start 9 specifically in connection with Mr. Wesbecker, Doctor Breggin, 10 that you feel relevant or important for the jury to know about 11 your review of the literature, about your review of the 12 serotonin system, about your review of FDA documents, about 13 anything in conferences you learned, any conversations with 14 the Food and Drug Administration officials, anything else that 15 is of importance in describing this phenomena or supporting 16 your opinion, sir? 17 A. Let me briefly just mention my clinical 18 experience. Naturally -- 19 MR. FREEMAN: Your Honor, I don't believe that 20 would be relevant. He hadn't talked about that on any opinion 21 he's given us and it would be anecdotal in nature and not 22 relevant material. 23 DOCTOR BREGGIN: I provided reports to you, sir. 24 JUDGE POTTER: Well, wait just a second, Doctor. 25 I'm going to sustain the objection if he's just 193 1 going to tell about two or three or whatever patients he's 2 had. 3 Q. Well, have you had experience in dealing with 4 people who have become violent and aggressive in -- 5 MR. FREEMAN: That's not appropriate, Your 6 Honor. 7 JUDGE POTTER: He's trying to lay some 8 groundwork. 9 Go ahead, Mr. Smith. 10 Q. -- in connection with use of psychotropic 11 medications? 12 A. Yes, sir. 13 Q. And has that been helpful to you in reviewing 14 this data and coming to conclusions in this case? 15 A. Yes. I've been helped by the reports I hear 16 from other mental health professionals when I give day-long 17 workshops; I have been helped by the patients who come to me; 18 and I've been helped by some very lengthy analyses, really 19 in-depth analyses that I've done of people who've committed 20 violent acts while on Prozac. 21 Q. Wait a minute. Are you saying that you 22 personally have talked with individuals who have had adverse 23 experiences with Prozac? 24 A. Oh, innumerable individuals in various parts of 25 the country when I do workshops. And some cases, where for 194 1 one reason or another, I have to do really in-depth reports. 2 Q. Have you talked with doctors who have had 3 patients who have had experiences with violent-aggressive 4 behavior while on Prozac? 5 MR. FREEMAN: Same objection, Judge. This is 6 not subject to confirmation; it's hearsay. 7 JUDGE POTTER: He's trying to lay a groundwork. 8 Q. Have you talked with family members who have had 9 family members and loved ones who have become violent and 10 aggressive while on Prozac? 11 A. Many, sir. Many. 12 Q. And do you take these conversations with 13 patients who have actually taken the drug, these conversations 14 with physicians who have actually prescribed the drug and 15 these conversations with family members of individuals who 16 have had this experience as relevant in making some type of 17 judgment as a professional concerning the relationship of 18 Prozac and violent-aggressive behavior? 19 A. Very much so. 20 Q. Anything else that you've experienced or done 21 that helped you in coming to conclusions concerning this drug 22 and whether it's related to violent-aggressive behavior in 23 some people? 24 A. I think I've covered what I wish to cover, sir. 25 Q. Thank you. 195 1 May we approach the bench, Your Honor? 2 JUDGE POTTER: Okay. 3 (BENCH DISCUSSION) 4 MR. SMITH: I am at a point where I'm going to 5 switch to Mr. Wesbecker. It's 20 till. We have had a long 6 and somewhat tedious day. 7 JUDGE POTTER: Okay. I'm sure it's fine with 8 the jury, too. 9 (BENCH DISCUSSION CONCLUDED) 10 JUDGE POTTER: Ladies and gentlemen, we're going 11 to take the evening recess. We'll quit a little early. I'm 12 going to give you the same admonition I've given you before. 13 Do not permit anybody to speak to or communicate with you 14 about any topic connected with this trial, and that includes 15 the news media. 16 I'm going to make one other suggestion. 17 Mr. King, I have a son that's a little older than you are and 18 I have a son that's a little younger than you are, and I 19 realize these children are paying absolute attention when I 20 think they're not; they're just kind of sitting there and 21 they're paying attention. But sometimes, you know... All I'm 22 going to say is maybe you're staying up late at night or 23 something like that. So could you kind of maybe get to bed 24 early tonight for me? Okay? 25 JUROR KING: Okay. 196 1 JUDGE POTTER: As I say, I don't mean to suggest 2 that you aren't, because my children a lot of times are paying 3 attention and I don't appreciate it, but maybe you have had a 4 few nights where you haven't been getting enough sleep. 5 Again, don't talk about the case among 6 yourselves, don't read anything about the topic in the 7 newspaper or hear it on television or whatever. Do not form 8 or express opinions about it. We'll stand in recess till 9:00 9 tomorrow morning. 10 (JURORS EXCUSED AT 4:43 P.M.) 11 * * * 12 13 14 15 16 17 18 19 20 21 22 23 24 25