David Healy is an Irish psychiatrist who is currently Reader in Psychological Medicine at Cardiff University College of Medicine, Wales. Psychiatry is a branch of medicine that studies and treats mental and emotional disorders (see mental illness). ... In the academic hierarchy in the United Kingdom and some universities in Australia and New Zealand, Reader is the rank between senior lecturer (or principal lecturer in the New Universities) and professor. ... The main building of Cardiff University Wikimedia Commons has media related to: Cardiff University Cardiff University (Welsh: Prifysgol Caerdydd) is a leading university located in the civic centre of Cardiff, Wales. ... This article is about the country. ...

Healy was born in Raheny, Dublin. He completed an MD in neuroscience and studied psychiatry during a clinical research fellowship at Cambridge University Clinical School. In 1990, Healy became a Senior Lecturer in Psychological Medicine at North Wales and in 1996 became a Reader in Psychological Medicine. His current research interests at Cardiff University include: cognitive functioning in affective disorders and psychoses as well as circadian rhythms in affective disorders. Healy has authored a number of books and is a world expert on the history and development of psychopharmacology. Raheny (Ráth Éanna in Irish) is a quiet northern suburb of Dublin, the capital city of the Republic of Ireland. ... WGS-84 (GPS) Coordinates: 53. ... Drawing of the cells in the chicken cerebellum by S. Ramón y Cajal Neuroscience is a field that is devoted to the scientific study of the nervous system. ... The University of Cambridge is the second-oldest university in the English-speaking world, with one of the most selective sets of entry requirements in the United Kingdom. ... Approximate extent of North Wales North Wales (known in some archaic texts as Northgalis) is the northernmost unofficial region of Wales, bordered to the south by Mid Wales. ... Psychosis is a psychiatric classification for a mental state in which the perception of reality is distorted. ... The Circadian rhythm is a name given to the internal body clock that regulates the (roughly) 24 hour cycle of biological processes in animals and plants. ... Psychopharmacology is the study of the effects of any psychoactive drug that acts upon the mind by affecting brain chemistry. ...

Healy became the centre of controversy concerning the influence of the pharmaceutical industry on medicine and academia. For most of his career Healy has held the view that Prozac and SSRIs (selective serotonin re-uptake inhibitors) can lead to suicide and has been critical of the amount of ghost writing in the current scientific literature. Healy's views led to what has been termed “The Toronto Affair” which at its core was a debate about academic freedom. This is a list of pharmaceutical and biotech companies that are major manufacturers on global or national markets : Abbott Laboratories Able Laboratories Akzo Nobel Allergan Almirall Prodesfarma Alphapharm Altana (previously Byk Gulden) ALZA, part of Johnson & Johnson Amgen AstraZeneca, formed from the merger of Astra AB and Zeneca Group PLC... Medicine is a branch of health science and the sector of public life concerned with maintaining or restoring human health through the study, diagnosis, treatment and possible prevention of disease and injury. ... Plato is credited with the inception of academia: the body of knowledge, its development and transmission across generations. ... Background Fluoxetine hydrochloride (brand names include Prozac®, Symbyax® (compounded with olanzapine), Sarafem®, Fontex® (Sweden), Fluctine (Austria, Germany), Prodep (India), Fludac (India)) is an antidepressant drug used medically in the treatment of depression, obsessive-compulsive disorder, bulimia nervosa, premenstrual dysphoric disorder, and many other disorders. ... Selective serotonin reuptake inhibitors (SSRIs) are a class of antidepressants used in the treatment of depression, anxiety disorders and some personality disorders. ... Serotonin (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract. ... Suicide (from Latin sui caedere, to kill oneself) is the act of willfully ending ones own life. ... A ghostwriter is an author who writes under someone elses name, with their consent. ... Academic freedom is the freedom of teachers, students, and academic institutions to pursue knowledge wherever it may lead, without undue or unreasonable interference. ...

SSRIs, Suicide and Healy

SSRIs

SSRIs are selective serotonin re-uptake inhibitors which are used to treat clinical depression. At one time it was thought that depression was due to low levels of serotonin in the brain. However, since 1970 scientists have known that depression is not caused by lowered serotonin levels. Nonetheless SSRIs were marketed and used to treat depression. Clinical depression (also called major depressive disorder) is a state of intense sadness, melancholia or despair that has advanced to the point of being disruptive to an individuals social functioning and/or activities of daily living. ...

Prozac is the most well known SSRI. In the 1970’s Bryan Molloy at Eli Lilly and Company created a phenoxyphenyl-propylamines termed LY-94949 but it could not be easily dissolved so David Wong reformulated it as a chloride salt and it was renamed LY-110140. Then on September 1, 1975 it was first called fluoxetine and then later marketed under the name Prozac. Prozac was launched in the United States and Canada in 1988 and in the United Kingdom in 1989. Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... September 1 is the 244th day of the year (245th in leap years) in the Gregorian calendar. ... 1975 (MCMLXXV) was a common year starting on Wednesday. ... Fluoxetine hydrochloride is an antidepressant drug used medically in the treatment of depression, body dysmorphic disorder, obsessive-compulsive disorder, bulimia nervosa, premenstrual dysphoric disorder, hypochondriasis and panic disorder. ...

Soon after its launch there was a large debate on whether or not Prozac was related to suicide.

Does Prozac Cause Suicide?

The debate was started by Martin Teicher from Harvard when they published an article in the American Journal of Psychiatry in 1990. The article outlined six individual cases of people who had become preoccupied with thoughts of suicide after going on Prozac. Harvard University is a private university in Cambridge, Massachusetts, USA, and a member of the Ivy League. ... kkdkd ...

Eli Lilly was quick to respond with a contradictory article by Charles Beasley and colleagues from Eli Lilly that examined evidence from 3,065 patients of which 1,700 had been put on Prozac. The authors concluded that there was no evidence for individuals taking Prozac to have a higher rate of suicide than those taking placebo. In his book, “Let Them Eat Prozac”, Healy points out several flaws in the Beasley experiment. In Healy’s view the entire experimental analysis rested on one question from the Hamilton Depression Rating Scale which is too insensitive to accurately measure suicidality. // A placebo is a medicine or preparation which has no inherent pertinent pharmacologic activity but which is effective only by virtue of the factor of suggestion attendant upon its administration. ... The Hamilton Depression Rating Scale is a 21-question multiple choice questionnaire which doctors may use to rate the severity of a patients depression. ...

The question reads: “This past week, have you had any thoughts that life is not worth living, or that you’d be better off dead? What about thoughts of hurting or even killing yourself?”

There are four choices from which the patient can choose: 1) has made a serious suicide attempt, 2) has clear suicidal ideas or gestures, 3) wished he were dead or any thoughts of possible death, 4) feels life is not worth living or absent. The problem that Healy has with this that the “Raters rate in a global way. If a patient is improving raters whiz through an interview, often completing the scale afterward in a manner that indicates a general improvement in the overall score. If some aspects of the patient’s condition are improving – which they might even when the patient is becoming suicidal – raters often won’t bother asking the suicide question.”

A second problem with that rating system is that if a significant number of people improve, their scores will drown out the noise being produced by patients who have worsened.

The debate centered around the question of which was more important, a handful of individual cases or a large randomized control trial. Healy believes that Prozac induces suicide. His comments in 1994 in CNS Drugs are often misquoted. Healy wrote that “data from several thousand patients must on any scientific scale outweigh the dubious evidence of a handful of case reports.” However, according to Healy this was a “piece of irony” and the “article came down firmly on the side of saying that Prozac did cause suicide” In addition Healy believes that the problem could be managed with proper warnings.

Lilly’s Knowledge of Prozac and Suicide

In “Let them Eat Prozac” Healy presents evidence that Eli Lilly already knew in 1986 that patients on Prozac attempted more suicides than patients on other anti-depressants and placebo. A memo from Barbara von Keitz, who was working in Germany for Eli Lilly, was sent to Joachim Wernicke at Eli Lilly Headquarters in Indianapolis. A result of a clinical trial showed that patients on Prozac had rate of suicide attempts of 10 per 1000 but those patients randomized to other anti-depressants (imipramine, amitripyline, doxepin or mainserin) had a rate of only 1.5/1000. Placebo patients had a varying rate or 6, 4.3 or 1 per 1000. Background Fluoxetine hydrochloride (brand names include Prozac®, Symbyax® (compounded with olanzapine), Sarafem®, Fontex® (Sweden), Fluctine (Austria, Germany), Prodep (India), Fludac (India)) is an antidepressant drug used medically in the treatment of depression, obsessive-compulsive disorder, bulimia nervosa, premenstrual dysphoric disorder, and many other disorders. ... The Indianapolis skyline Indianapolis is the capital of the U.S. state of Indiana. ...

The varying placebo rate is due to suicide attempts during the washout period being placed in the placebo groups. Healy sees this experimental method as “highly inappropriate”. There are two appropriate ways to respond. One is to count only the five suicide attempts in the placebo group which would give a rate of 4.3/1000. The second is to count all the patients that went into clinical trials as placebo which would give a rate of 1.0/1000.

The signs of violence and suicidality were there since Prozac (fluoxetine) was tested in premarketing trials.

In May 1984, Germany’s regulatory agency (GBA) rejected Prozac as “totally unsuitable for treating depression.” In July 1985, Eli Lilly’s own data analysis—from a pool of 1,427 patients—showed high incidence of adverse drug effects and evidence of drug-induced violence in some patients.^[1] In May 1985, FDA’s (then) chief safety investigator, Dr. Richard Kapit, wrote: “Unlike traditional tricyclic antidepressants fluoxetine’s profile of adverse side effects more closely resembles that of a stimulant drug than one that causes sedation.” He warned “It is fluoxetine’s particular profile of adverse side-effects which may perhaps, in the future give rise to the greatest clinical liabilities in the use of this medication to treat depression.”^[2] One of the worlds largest corporations, Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company with headquarters in Indianapolis,Indiana, USA. A Fortune 500 corporation, the company had revenues of $12. ...

Dr. Kapit’s safety review described the clinical trial data from 46 trials with a total of 1,427 patients. He noted under the section, “Catastrophic and Serious Events,” 52 cases of “egregiously abnormal laboratory reports which were the reason for early termination,” and “additional adverse event reports not reported by the company [which] were revealed on microfiche.” Dr. Kapit reported: “In most cases, these adverse events involved the onset of an unreported psychotic episode.” There were 10 reports of psychotic episodes; 2 reports of completed suicides; 13 attempted suicides; 4 seizures—including a healthy volunteer; and 4 reports of movement disorders.

In 1985 Dr. Kapit recommended “labeling warning [for] the physician that such signs and symptoms of depression may be exacerbated by this drug". No such warning was issued until 2004.

In 2005, an internal document purportedly from Eli Lilly and Co. made public showed that the drug maker had data more than 15 years old showing that patients on its antidepressant Prozac were far more likely to attempt suicide and show hostility than were patients on other antidepressants and that the company attempted to minimize public awareness of the side effects. The 1988 document indicated that 3.7 percent of patients attempted suicide while on the blockbuster drug, a rate more than 12 times that cited for any of four other commonly used antidepressants. The document, which cited clinical trials of 14,198 patients on fluoxetine also stated that 2.3 percent of users suffered psychotic depression while on the drug, more than double the next-highest rate of patients using another antidepressant.

The document was provided to CNN by the office of Rep. Maurice Hinchey, D-New York, who called for tightening FDA regulations on drug safety. "The case demonstrates the need for Congress to mandate the complete disclosure of all clinical studies for FDA-approved drugs so that patients and their doctors, not the drug companies, decide whether the benefits of taking a certain medicine outweigh the risks," Rep. Hinchey said. The Cable News Network, commonly known as CNN, is a major cable television network founded in 1980 by Ted Turner. ...

Tobin vs. SmithKline; SSRIs in Court

In February of 1998, Donald Schell, a 60-year old, went to see his doctor complaining of difficulty sleeping. He was diagnosed with an anxiety state and placed on Paxil, an SSRI. Within forty-eight hours of being put on Paxil Schell killed his wife, daughter, infant grand-daughter, and himself. Tim Tobin, Schell’s son-in-law took legal action against SmithKline. Healy was retained as an expert witness in the case. Paroxetine (paroxetine hydrochloride; trade names Paxil® (United States), Seroxat® (UK), Aropax® (Australia)) is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) type. ...

The Tobin case was heard in Cheyenne, Wyoming from May 21 to June 6, 2001. On the stand SmithKline representative Ian Hudson indicated that no matter how many physicians or clinicians reported to the company that they thought suicide was related to the Paxil, SmithKline would deny causation. The jury returned a guilty verdict against SmithKline and awarded Tobin eight million dollars. This was the first verdict returned guilty against a pharmaceutical company regarding adverse behavioral effects of a psychotropic drug. Cheyenne lodges with buffalo meat drying, 1870 For other uses, see Cheyenne (disambiguation). ... Official language(s) English Capital Cheyenne Largest city Cheyenne Area  Ranked 10th  - Total 97,818 sq mi (253,348 km²)  - Width 280 miles (450 km)  - Length 360 miles (580 km)  - % water 0. ... May 21 is the 141st day of the year in the Gregorian calendar (142nd in leap years). ... June 6 is the 157th day of the year in the Gregorian calendar (158th in leap years), with 208 days remaining // 1508 - Maximilian I, Holy Roman Emperor, is defeated in Friulia by Venetian forces; he is forced to sign a three-year truce and cede several territories to Venice 1513... This article is about the year 2001. ...

Healy’s Healthy Volunteer Study

Healy designed an experiment to examine if disinhibition, which Healy believes can lead to suicide, is associated with SSRIs. He compared Zoloft (an SSRI) to reboxetine (a non-SSRI anti-depressant) in a group of healthy volunteers. The volunteers would be placed on Zoloft or reboxetine for two weeks, halt for two weeks and then take the other drug for two weeks. The experiment would test if the marketed “better than well” phenomenon for SSRI was true. Sertraline hydrochloride (Zoloft®, Lustral®, Apo-Sertral®, Asentra®, Gladem®, Serlift®, Stimuloton®) is an orally administered antidepressant of the selective serotonin reuptake inhibitor (SSRI) type. ... Reboxetine is an antidepressant drug used in the treatment of clinical depression, panic disorder and ADD/ADHD. Its mesilate ( methanesulfonate) salt is sold under tradenames including Edronax®, Norebox®, Prolift®, Solvex® or Vestra®. Reboxetine has two chiral centers, but it only exists as two enantiomers, (R,R)-(-)- and (S,S)-(+)-reboxetine. ...

At the end of the study two-thirds of the participants rated themselves as “better than well”. However, the volunteers’ quality of life and social functioning decreased on Zoloft but remained the same on reboxetine. Approximately half the group reported emotional blunting on the drugs.

Two patients in the study became suicidal which Healy associated with disinhibition caused by Zoloft. One patient highlighted the trend of suicide by hanging which is a trend in SSRI suicides. Healy calculated the probability of two healthy volunteers without mental illness and no current interpersonal legal or financial problems becoming suicidal during a two week period on Zoloft as p = 0.0000005. In other words, the chance that Zoloft was unrelated to the two healthy volunteers' becoming suicidal during the trial period (that is, the chance that it was coincidental) is only 1 in 2000000.

Healy concluded that he had “accidentally demonstrated conclusively that the drugs could cause the problem”

The Toronto Affair

On August 17, 2000 Dr. David Goldbloom, the Physician-in-Chief at the Centre for Addiction and Mental Health (CAMH) and a Professor of Psychiatry and the University of Toronto, wrote to Healy to formally offer him “the position of Clinical Director, Mood and Anxiety Disorder Program, CAMH”. August 17 is the 229th day of the year (230th in leap years) in the Gregorian Calendar. ... This article is about the year 2000. ... The Centre for Addiction and Mental Health, ARF Site The Centre for Addiction and Mental Health (CAMH) is a consortium of mental health clinics at several sites in Toronto, Ontario. ... The University of Toronto (U of T) is a coeducational public research university in Toronto, Ontario. ...

The Lecture

On November 30, 2000 Healy was invited to a meeting at the University of Toronto entitled “Look Back. Looking Ahead – Psychiatry in the 21st Century: Mental Illness and Addiction”. Healy presented a talk with the title “Psychopharmacology and the Government of Self”. This talk gave an overview of the history of psychopharmacology and was critical of several aspects of the pharmaceutical industry. November 30 is the 334th day (335th on leap years) of the year in the Gregorian Calendar, with 31 days remaining. ... This article is about the year 2000. ...

Healy talked about the inadequacy of clinical trials stating that “clinical trials in psychiatry have never showed that anything worked”. His point was that clinical trials demonstrate treatment effects and not whether or not a drug works. Also critical of ghost-written scientific literature; he noted that the fact that unsuccessful clinical trials are suppressed and successful clinical trials are over reported was not science. In medicine, a clinical trial (synonyms: clinical studies, research protocols, medical research) is a research study. ...

In addition, Healy made the direct comment that “Prozac and other SSRIs can lead to suicide" and that “these drugs may have been responsible for 1 death for everyday that Prozac has been on the market in North America”. Moreover, Healy criticized the industry by the fact that “since the controversy blew up, there has not been a single piece of research carried out to answer the question of whether ‘Prozac’ does cause suicide or not”.

The Aftermath

On December 7, 2000, shortly after Healy’s talk he received an email from Dr. Goldbloom, who was retracting his previously offered position at CAMH. The reason Goldbloom indicated was as follows: “Essentially, we believe that it is not a good fit between you and the role as leader of an academic program in mood and anxiety disorders at the Centre and in relation to the University. This view was solidified by your recent appearance at the Centre in the context of an academic lecture. While you are held in high regard as a scholar of the history of modern psychiatry, we do not feel your approach is compatible with the goals for development of the academic and clinical resource that we have.” However, Healy believes that his job offer was retracted because his critical views of the pharmaceutical industry and especially Eli Lilly. This has been denied by the President of the University of Toronto, Dr. Robert Birgeneau who stated in a letter to the Canadian Association of University Teachers (CAUT) that Healy’s contract was “not influenced in any way by Eli Lilly or by any other pharmaceutical company.” December 7 is the 341st day (342nd in leap years) of the year in the Gregorian calendar. ... This article is about the year 2000. ... One of the worlds largest corporations, Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company with headquarters in Indianapolis,Indiana, USA. A Fortune 500 corporation, the company had revenues of $12. ...

Eli Lilly was a significant contributor to the University of Toronto. It supported 52% of the budget for the Mood and Anxiety Disorder Clinic that Healy would have headed up. In addition it gave a 1.5 million dollar gift to CAMH to help its fundraising campaign. Furthermore, there was precedent for Eli Lilly removing its financial in response to anti-Prozac comments or publications. In March of 2000, the Hasting Center published an article by Healy which indicated that Prozac induced suicide. Eli Lilly pulled their support of $25,000 per annum. The Hasting Center re-reviewed the article but stood behind its decision. One of the worlds largest corporations, Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company with headquarters in Indianapolis,Indiana, USA. A Fortune 500 corporation, the company had revenues of $12. ... The University of Toronto (U of T) is a coeducational public research university in Toronto, Ontario. ...

The Canadian Association of University Teachers (CAUT) fully supported Healy and lobbied the University of Toronto on his behalf. In one letter to President Birgeneau, in March of 2001 they stated “retraction of a job offer suggests a fundamental attack on academic freedom…what happened to Dr. Healy appears to be an affront to academic freedom in Canada.” The CAUT was concerned that CAMH and the University of Toronto were concerned about employing a widely recognized critic, who raises questions about corporate connections and how this might impact funding.

In September of 2001, Healy filed a lawsuit against the CAMH and the University of Toronto for 9.4 million dollars in damages and lost income. In a press conference Healy stated that his greatest concern was academic freedom and that with some of the damages awarded he would set up a fund to promote academic freedom. The lawsuit settled out of court and many of the terms of settlement remain undisclosed; but the settlement did result in Healy being offered a visiting professorship at the University of Toronto.

Ghost Writing

Medical ghost writing occurs when people with scientific backgrounds are paid to stay anonymous and produce favorable reports for drug companies then doctors are added to these studies for money, prestige or perks. Healy estimates that up to 50% of literature on drugs is ghost written. Ghost writers write on research given to them by drug companies, which want both positive results and positive research; therefore ghost writing is biased from the beginning.

Healy had an encounter with ghost writing gone wrong involving Wyeth’s SSRI Effexor. Healy attended a meeting promoting Effexor and was given the opportunity to have an article ghost written. When he received that first draft he left the main article intact but made two additions. One that contradicted Wyeth’s claim that Effexor got patients fully well compared to patients on other SSRIs and that SSRIs could make some individuals suicidal. The article went through more reviews and was already submitted to the Journal of Psychiatry and Neuroscience before Healy saw it again; both of Healy’s inserts had been removed. In response Healy removed his name from the article. Wyeth, formerly known as American Home Products, is one of the largest pharmaceutical companies in the world. ... Venlafaxine hydrochloride is a prescription antidepressant first introduced by Wyeth in 1993, and marketed under the tradename Effexor®. It is used primarily for the treatment of depression, generalized anxiety disorder, and social anxiety disorder in adults. ...

Healy believes that ghost writing is not all evil but insists that to be honest the raw data must be made available.

Solutions

In the preface of “Let them Eat Prozac” Healy describes the need for a “new contract between society and the pharmaceutical industry – a contract that will require access to the raw data”. Healy suggests a new division that can manage the hazards that only becomes visible after products are launched. This new division would be separate from the regulatory bodies and pharmaceutical companies.

Selected bibliography

• The Psychopharmacologists Vol I (1996) ISBN 1-86036-008-4
• The Antidepressant Era (1998) ISBN 0-674-03958-0
• Psychiatric Drugs Explained (2001) ISBN 0-443-07018-0
• The Creation of Psychopharmacology (2002) ISBN 0-674-00619-4
• Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression (2004) ISBN 0-8147-3669-6

Resources

Ashcroft G. The receptor enters psychiatry. In Healy D. The Psychopharmacologists Vol 3 (London: Arnold, 2000), 189-200

Teicher MH, Glod C, Cole JO. Emergence of intense suicidal preoccupation during fluoxetine treatment. American Journal of Psychiatry 147 (1990), 207-210

Beasley CM, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH, Heiligenstein JH et al. Fluoxetine and suicide: a meta-analysis of controlled trials of treatment of depression. British Medical Journal 3-3 (1991), 685-92

Healy D, The fluoxetine and suicide controversy. CNS Drugs 1 (1994), 252-4

Memo from B von Keitz and H Weber to J Wernicke: Fluoxetine suicides and suicide attempts, October 1986, Exhibit 19 in the deposition of Joachim Wernick in Fentress Vs. Eli Lilly

Tranter R, Healy H, Cattel D, Healy D. Functional variation in agents differentially selective to monoaminergic systems. Psycological Medicine 32, 517-24

External links

• David Healy's homepage
• The David Healy Affair archive
• Healy settles lawsuit with University of Toronto
• Is Academic Psychiatry for Sale ? - debate between David Healy and Michael Thase published in the British Journal of Psychiatry
• Let Them Eat Prozac Details about Healy's case and material on the link between SSRIs and suicide.
• "They said it was safe" Guardian article on Healy's role in Forsyth case
• Video of Loren Mosher, M.D. (first Chief of Schizophrenia Studies at NIMH and founding editor of the Schizophrenia Bulletin) discussing the importance of David Healy's research in making true informed consent regarding the SSRI's possible for the first time