David Healy (psychiatrist)
David Healy is an Irish psychiatrist who is a professor in Psychological Medicine at Cardiff University School of Medicine, Wales. He is also the director of North Wales School of Psychological Medicine. He 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 was, at its core, a debate about academic freedom.
 Background and research
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. In 1996 he became a Reader in Psychological Medicine, then later became Professor. His current research interests at Cardiff University include: cognitive functioning in affective disorders and psychoses as well as circadian rhythms in affective disorders, recovery in psychoses and physical health of people with mental illness.
He also heads the psychiatric inpatient unit at Bangor, North Wales, where treatments include electroconvulsive therapy (ECT) and psychiatric medication. Healy has authored a number of books and is an expert on the history and development of psychopharmacology. He co-authored a book, History of Convulsive Therapy with Edward Shorter. Healy’s work, particularly his histories of psychopharmacology, influenced Charles Barber's book Comfortably Numb: How Psychiatry Is Medicating a Nation.
 SSRIs, suicide and Healy
Selective serotonin re-uptake inhibitors (SSRIs) are used to treat major depression. At one time it was hypothesized that depression was due to low levels of serotonin in the brain and that antidepressants increased this level. But this theory was discredited by Ashcroft who showed that depression is not associated with or caused by a lowering of serotonin. Today, serotonin levels can be measured by 5-HT imaging with Positron emission tomography (PET) imaging as well as measuring tryptophan plasma levels.
Prozac is a well known commercial brand of SSRI. In the 1970s 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.
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 being prescribed Prozac.
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.
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:
- "The best management of such reactions will involve counselling patients beforehand about the possibility of these reactions, stopping treatment with the agents if such a reaction is suspected, or adding an agent with 5-HT1A antagonistic properties (e.g. propranolol) to the treatment regimen."
 Lilly’s knowledge of Prozac and suicide
In Let them Eat Prozac, Healy presents evidence that Eli Lilly already knew in 1986 that patients taking Prozac attempted more suicides than patients taking other anti-depressants or a 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 taking Prozac had a suicide attempt rate of 10 per 1000 but those patients randomized to other anti-depressants (imipramine, amitriptyline, doxepin or mainserin) had a rate of only 1.5 per 1000. Placebo patients had varying rates of 6, 4.3 or 1 per 1000.
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.
Signs of violence and suicidality had been there since Prozac was tested in premarketing trials.
In May 1984, Germany’s regulatory agency (BGA) 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. 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.”
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.
 Tobin vs. SmithKline
In February 1998, 60-year-old Donald Schell 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 granddaughter, and himself. Tim Tobin, Schell’s son-in-law, took legal action against SmithKline. Healy was retained as an expert witness in the case.
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 $6.4 million. This was the first verdict returned guilty against a pharmaceutical company regarding adverse behavioral effects of a psychotropic drug.
 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.
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's experience highlighted the theme of hanging, which is common 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.
 Toronto affair
In 1999, the British citizen Healy had been actively recruited for a position in the Department of Psychiatry and the Centre for Addiction and Mental Health (CAMH) in Toronto. He was brought in for a three-day visit to CAMH and the Department in July. Following his visit, Dr. Paul Garfinkel, Chair of the University's Department of Psychiatry, wrote him a congratulatory letter.
On January 28, 2000 Dr. Sidney Kennedy, Professor or Psychiatry and Head, Mood & Anxiety Division, CAMH, wrote to Healy discussing details of an offer to be appointed a Professor of Psychiatry at the University of Toronto and Clinical Director for the Mood and Anxiety Disorders Program at CAMH. Kennedy concluded: "I am extremely enthusiastic about your interest in this position and I believe that you will bring an important line of critical inquiry and clinical research acumen to this department".
On August 17, 2000 Dr. David Goldbloom, Physician-in-Chief at CAMH and Professor of Psychiatry at University of Toronto, and Georgina Veldhorst, Vice-President, Mental Health Programs, CAMH, wrote to Healy to offer him formally the position of Clinical Director, Mood and Anxiety Disorders Program, CAMH.
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.
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. Healy was 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 scientifically sound.
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 one death for every day 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”.
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 then-President of the University of Toronto, Prof. 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.”
Eli Lilly was a significant contributor to the University of Toronto. It supported 52 percent 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 support in response to anti-Prozac comments or publications. In March 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.
The Canadian Association of University Teachers (CAUT) fully supported Healy and lobbied the University of Toronto on his behalf. In a May 2001 letter to Birgeneau, 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 2001, Healy filed a lawsuit against the CAMH and the University of Toronto for $9.4 million 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; following the settlement, Healy was offered and accepted a visiting professorship at the University of Toronto. In an interview about Healy's dismissal, a CAMH spokesperson "denied any influence on our decisions, direct or indirect or otherwise, by an outsider donor, funder, or individual and certainly not by a pharmaceutical company."
 Ghost writing
Medical ghost writing occurs when anonymous ghostwriters with scientific backgrounds are paid to produce reports for publication as if written by better-known experts. Healy estimates that up to 50 percent of literature on drugs is ghostwritten. In his thesis, he states that ghostwriters write on research given to them by drug companies, which want both positive results and positive research; therefore ghostwriting is biased from the beginning.
Healy encountered ghost writing involving Wyeth’s SNRI Effexor. Healy attended a meeting promoting Effexor, and was offered for his approval a draft article that had been written for him. He left it intact, but made two additions. One contradicted Wyeth’s claim that Effexor got patients fully well compared to patients on other SSRIs and another stated that SSRIs could make some individuals suicidal. The article had already been submitted to the Journal of Psychiatry and Neuroscience before Healy saw it again; both of his additions had been removed. In response Healy removed his name from the article.
In the preface of his book 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.
- "The literature profiles and citation rates of industry-linked and non-industry-linked articles differ. The emerging style of authorship in industry-linked articles can deliver good-quality articles, but it raises concerns for the scientific base of therapeutics."
He proposed the following resolution of this conflict of interest :
- "If ghostwriting is an inevitable feature of modern scientific writing, the potential availability of the raw data would do more to ensure a correspondence between those data and a published end result than could be achieved by any other mechanism."
 Editorial board membership
- The Psychopharmacologists Vol I (1996) ISBN 1-86036-008-4
- The Antidepressant Era Harvard University Press (1999) ISBN 978-0674039582
- The Psychopharmacologists II (1999) ISBN 1-86036-010-6
- The Psychopharmacologists III(Paperback 2000) ISBN 978-0340761106
- The Creation of Psychopharmacology (Paperback 2004) ISBN 978-0674015999
- Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression New York University Press (2004) ISBN 978-0814736975
- Shock Therapy: The History of Electroconvulsive Treatment in Mental Illness, with Edward Shorter. Rutgers University Press (2007) ISBN 0-8135-4169-7
- Mania: A Short History of Bipolar Disorder Johns Hopkins University Press (Paperback 2010) ISBN 978-1421403977
- Psychiatric Drugs Explained Churchill Livingston (Paperback 5th ed. 2011) ISBN 978-0702041365
- Pharmageddon University of California Press(2012) ISBN 978-0520270985
Ashcroft G. The receptor enters psychiatry. In Healy D. The Psychopharmacologists Vol 3 (London: Arnold, 2000), 189-200
Coyne J. Lessons in conflict of interest: The construction of the martyrdom of David Healy and the dilemma of bioethics. American Journal of Bioethics (2005) 5 (1): W3-W14.
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. Psychological Medicine 32, 517-24
 See also
- Joshua Kendall. Talking back to Prozac. Boston Globe, 1 February 2004.
- J.J.Schildkraut, "The Catecholamine Hypothesis of Affective Disorders: A Review of Supporting Evidence," American Journal Of Psychiatry 122 (1965): 519-22.
- Ashcroft, "The Receptor Enters Psychiatry," 189-200. Healy, D. Let Them Eat Prozac, pp.11-12, 2006.
- Gehlert DR, Schober DA, Hemrick-Luecke SK, Krushinski J, Howbert JJ, Robertson DW, Fuller RW, Wong DT. Novel halogenated analogs of tomoxetine that are potent and selective inhibitors of norepinephrine uptake in brain. Neurochem Int. 1995 Jan;26(1):47-52
- Meyer JH.Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci. 2007 Mar;32(2):86-102.
- David Healy The Fluoxetine and Suicide Controversy: A Review of the Evidence CNS Drugs. 1(3):223-231, March 1994
- Fax from the BGA to Eli Lilly, 25 May 1984
- Eli Lilly internal analysis submitted to the Joachim Wernicke (July 2, 1985), PZ 2441 2000. Document uncovered during Fentress litigation.
- Kapit R. FDA Safety Review NDA 18-963, March 23, 1985.
- Tobin v. SmithKline Verdict, June 6, 2001
- Tobin v. SmithKline Judgment, June 6, 2001
- The New York Times, Jury Awards $6.4 Million in Killings Tied to Drug, June 8, 2001
- Reis M, Aamo T, Ahlner J and Druid H. Reference Concentrations of Antidepressants-A Compilation of Postmortem & Therapeutic Levels, Journal of Analytical Toxicology, Vol 31, June 2007
- D. Healy, "Let Them Eat Prozac", Chapter 7, 2004.
- D. Healy, "Emergence of Antedepressant Induced Suicidality, "Primary Care Psychiatry" 6 (2000): 23-28.
- CAUT Letter to President Birgeneau, March 29, 2001
- Full-text of the lecture "Psychopharmacology and the Government of Self"
- The E-Mails : Dr Healy's job offer at Centre for Addiction and Mental Health is rescinded
- Canadian University of Toronto Again Letter to President Birgeneau, April 30, 2001
- The Canadian University of Toronto Get Involved
- Sept 24th 2001 Press Conference Transcript
- Joshua Kendall Talking back to Prozac The Boston Globe, February 1, 2004
- Antony Barnett Revealed: how drug firms 'hoodwink' medical journals The Observer, 7 December 2003
- Sarah Boseley 'It said the drug was the best thing since sliced bread. I don't think it is' Guardian, February 7, 2002
- Healy, D., & Cattell, D.Interface between authorship, industry and science in the domain of therapeutics The British Journal of Psychiatry (2003) 183: 22-27.
- Hon Int Ed Adv Board of the Mens Sana Monographs
- David Healy's site to research and report drug side effects
- David Healy's blog
- 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
- Barry Yeoman, Putting Science in the Dock, The Nation
- David Healy The Future of Medical Care: Can Industrialized and Marketized Healthcare be Made Universally Available?, Nordlander Lecture Series, Cornell University 25 March 2009
- David Healy One Side of the Background to an Academic Freedom Dispute Academy for the Study of the Psychoanalytic Arts
- Jennifer Hansen Book review - Let Them Eat Prozac Metapsychology, 26 July 2005 (Volume 9, Issue 30)