David Healy (psychiatrist)
Encyclopedia
David Healy is an Irish
psychiatrist
who is currently 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
.
, 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. He became a Professor a couple of years ago. 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.
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.
in 1990. The article outlined six individual cases of people who had become preoccupied with thoughts of suicide after going on 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."
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, amitriptyline
, 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.
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 (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.
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.
(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 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.”
(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.
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”.
“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."
s 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 "Interface between authorship, industry and science in the domain of therapeutics" a paper of 2003 for The British Journal of Psychiatry
, David Healy notes that :
"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 propose 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."
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
Ireland
Ireland is an island to the northwest of continental Europe. It is the third-largest island in Europe and the twentieth-largest island on Earth...
psychiatrist
Psychiatrist
A psychiatrist is a physician who specializes in the diagnosis and treatment of mental disorders. All psychiatrists are trained in diagnostic evaluation and in psychotherapy...
who is currently a professor in Psychological Medicine at Cardiff University School of Medicine
Cardiff University School of Medicine
Cardiff University School of Medicine was founded in 1893 when the Departments of Anatomy, Physiology, Pharmacology, Pathology, Bacteriology were founded at University College of South Wales and Monmouthshire , in the same year. Students finishing their preclinical studies at Cardiff went on to...
, Wales
Wales
Wales is a country that is part of the United Kingdom and the island of Great Britain, bordered by England to its east and the Atlantic Ocean and Irish Sea to its west. It has a population of three million, and a total area of 20,779 km²...
. 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
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
and academia
Academia
Academia is the community of students and scholars engaged in higher education and research.-Etymology:The word comes from the akademeia in ancient Greece. Outside the city walls of Athens, the gymnasium was made famous by Plato as a center of learning...
. For most of his career Healy has held the view that Prozac and SSRIs
Selective serotonin reuptake inhibitor
Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...
(selective serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
re-uptake inhibitors) can lead to suicide
Suicide
Suicide is the act of intentionally causing one's own death. Suicide is often committed out of despair or attributed to some underlying mental disorder, such as depression, bipolar disorder, schizophrenia, alcoholism, or drug abuse...
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
Academic freedom
Academic freedom is the belief that the freedom of inquiry by students and faculty members is essential to the mission of the academy, and that scholars should have freedom to teach or communicate ideas or facts without being targeted for repression, job loss, or imprisonment.Academic freedom is a...
.
Background and research
Healy was born in RahenyRaheny
Raheny is a northern suburb of Dublin, the capital city of Ireland. It is an old area, centred around an old village, and is referenced back to 570 AD but after years of light settlement, with a main village and a coastal hamlet, grew rapidly in the 20th century, and is now a mid-density...
, Dublin. He completed an MD in neuroscience
Neuroscience
Neuroscience is the scientific study of the nervous system. Traditionally, neuroscience has been seen as a branch of biology. However, it is currently an interdisciplinary science that collaborates with other fields such as chemistry, computer science, engineering, linguistics, mathematics,...
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
North Wales
North Wales is the northernmost unofficial region of Wales. It is bordered to the south by the counties of Ceredigion and Powys in Mid Wales and to the east by the counties of Shropshire in the West Midlands and Cheshire in North West England...
and in 1996 became a Reader in Psychological Medicine. He became a Professor a couple of years ago. 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
Bangor, Gwynedd
Bangor is a city in Gwynedd, north west Wales, and one of the smallest cities in Britain. It is a university city with a population of 13,725 at the 2001 census, not including around 10,000 students at Bangor University. Including nearby Menai Bridge on Anglesey, which does not however form part of...
, North Wales
North Wales
North Wales is the northernmost unofficial region of Wales. It is bordered to the south by the counties of Ceredigion and Powys in Mid Wales and to the east by the counties of Shropshire in the West Midlands and Cheshire in North West England...
, where treatments include electroconvulsive therapy
Electroconvulsive therapy
Electroconvulsive therapy , formerly known as electroshock, is a psychiatric treatment in which seizures are electrically induced in anesthetized patients for therapeutic effect. Its mode of action is unknown...
(ECT) and psychiatric medication
Psychiatric medication
A psychiatric medication is a licensed psychoactive drug taken to exert an effect on the mental state and used to treat mental disorders. Usually prescribed in psychiatric settings, these medications are typically made of synthetic chemical compounds, although some are naturally occurring, or at...
. Healy has authored a number of books and is an expert on the history and development of psychopharmacology
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...
. He co-authored a book, History of Convulsive Therapy with Edward Shorter. Healy’s work, particularly his histories of psychopharmacology, influenced Charles Barber's
Charles Barber (author)
Charles Barber is an author who writes frequently about mental health and psychiatry.-Education and Influences:Barber attended Harvard University, where he studied with and was greatly influenced by the psychiatrist and writer Robert Coles...
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 serotoninSerotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
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
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
(PET) imaging as well as measuring tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
levels.
Prozac is a well known commercial brand of SSRI. In the 1970s Bryan Molloy at Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
created a phenoxyphenyl-propylamines termed LY-94949 but it could not be easily dissolved so David Wong
David Wong
David Wong may refer to:* David Wong Louie, American writer of novels and short stories * Dave Wong , Chinese singer* David Wong , philosophy professor at Duke University...
reformulated it as a chloride salt and it was renamed LY-110140. Then on September 1, 1975 it was first called fluoxetine
Fluoxetine
Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company...
and then later marketed under the name Prozac. Prozac was launched in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
in 1988 and in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
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 PsychiatryAmerican Journal of Psychiatry
The American Journal of Psychiatry is a monthly peer-reviewed medical journal covering all aspects of psychiatry and the official journal of the American Psychiatric Association. The first volume was issued in 1844, at which time it was known as the American Journal of Insanity...
in 1990. The article outlined six individual cases of people who had become preoccupied with thoughts of suicide after going on 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
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
.
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
Hamilton Depression Rating Scale
The Hamilton Rating Scale for Depression , also known as the Hamilton Depression Rating Scale or abbreviated to HAM-D, is a multiple choice questionnaire that clinicians may use to rate the severity of a patient's major depression. Max Hamilton originally published the scale in 1960 and reviewed...
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 on Prozac attempted more suicides than patients on other anti-depressants and placebo. A memo from Barbara von Keitz, who was working in GermanyGermany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
for Eli Lilly, was sent to Joachim Wernicke at Eli Lilly Headquarters in Indianapolis
Indianapolis
Indianapolis is the capital of the U.S. state of Indiana, and the county seat of Marion County, Indiana. As of the 2010 United States Census, the city's population is 839,489. It is by far Indiana's largest city and, as of the 2010 U.S...
. 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, amitriptyline
Amitriptyline
Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs...
, 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.
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 (BGA) rejected Prozac as “totally unsuitable for treating depression.” In July 1985, Eli Lilly’s
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
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
CNN
Cable News Network is a U.S. cable news channel founded in 1980 by Ted Turner. Upon its launch, CNN was the first channel to provide 24-hour television news coverage, and the first all-news television channel in the United States...
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; SSRIs in Court
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
Cheyenne
Cheyenne are a Native American people of the Great Plains, who are of the Algonquian language family. The Cheyenne Nation is composed of two united tribes, the Só'taeo'o and the Tsétsêhéstâhese .The Cheyenne are thought to have branched off other tribes of Algonquian stock inhabiting lands...
, Wyoming
Wyoming
Wyoming is a state in the mountain region of the Western United States. The western two thirds of the state is covered mostly with the mountain ranges and rangelands in the foothills of the Eastern Rocky Mountains, while the eastern third of the state is high elevation prairie known as the High...
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
Causation in English law
Causation in English law concerns the legal tests of remoteness, causation and foreseeability in the tort of negligence. It is also relevant for English criminal law and English contract law....
. 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 reboxetineReboxetine
Reboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...
(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 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
In 1999, the British citizen Dr. David Healy had been actively recruited for a position in the Department of Psychiatry and the Centre for Addiction and Mental HealthCentre for Addiction and Mental Health
The Centre for Addiction and Mental Health is a consortium of mental health clinics at several sites in Toronto, Ontario, Canada. Its name in French is Centre de toxicomanie et de santé mentale...
(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
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
, 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.
The Lecture
On November 30, 2000 Healy was invited to a meeting at the University of TorontoUniversity of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
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
Psychopharmacology
Psychopharmacology is the scientific study of the actions of drugs and their effects on mood, sensation, thinking, and behavior...
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
North America
North America is a continent wholly within the Northern Hemisphere and almost wholly within the Western Hemisphere. It is also considered a northern subcontinent of the Americas...
”. 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
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
. This has been denied by the then-President of the University of Toronto, Prof. Robert Birgeneau
Robert Birgeneau
Robert Joseph Birgeneau is a Canadian physicist, educator, and university administrator. He is the ninth chancellor of the University of California, Berkeley, and was the fourteenth president of the University of Toronto from 2000 to 2004.-Biography:The first from his family to finish high school,...
who stated in a letter to the Canadian Association of University Teachers
Canadian Association of University Teachers
The Canadian Association of University Teachers is a federation of independent associations and trade unions representing approximately 65,000 teachers, librarians, researchers and other academic professionals and general staff at 120 universities and colleges across Canada.-Principal Aims:The...
(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
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
. 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 ghostwriterGhostwriter
A ghostwriter is a professional writer who is paid to write books, articles, stories, reports, or other texts that are officially credited to another person. Celebrities, executives, and political leaders often hire ghostwriters to draft or edit autobiographies, magazine articles, or other written...
s 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
Thesis
A dissertation or thesis is a document submitted in support of candidature for an academic degree or professional qualification presenting the author's research and findings...
, 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
Wyeth
Wyeth, formerly one of the companies owned by American Home Products Corporation , was a pharmaceutical company. The company was based in Madison, New Jersey, USA...
’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.
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.In "Interface between authorship, industry and science in the domain of therapeutics" a paper of 2003 for The British Journal of Psychiatry
British Journal of Psychiatry
The British Journal of Psychiatry is a peer-reviewed medical journal published monthly by the Royal College of Psychiatrists containing original research, systematic reviews, commentaries on contentious articles, short reports, a comprehensive book review section, and a correspondence column...
, David Healy notes that :
"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 propose 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
Healy sits on the Honorary International Editorial Advisory Board of the Mens Sana MonographsMens Sana Monographs
The Mens Sana Monographs is an open-access peer-reviewed medical journal-cum-monographic series. It is Devoted to the Understanding of Medicine, Mental Health, Mind, Man and their Matrix. The Mens Sana Monographs (MSM) is an open-access peer-reviewed medical journal-cum-monographic series. It is...
Selected bibliography
- The Psychopharmacologists Vol I (1996) ISBN 1-86036-008-4
- The Antidepressant Era (1998) ISBN 0-674-03958-0
- The Psychopharmacologists II (1999) ISBN 1860360106
- The Psychopharmacologists III(2000) ISBN 0340761105
- 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
- Shock Therapy: The History of Electroconvulsive Treatment in Mental Illness, with Edward Shorter. (2007) ISBN 0813541697
- Mania: A Short History of Bipolar Disorder (2008) ISBN 0801888220
Resources
Ashcroft G. The receptor enters psychiatry. In Healy D. The Psychopharmacologists Vol 3 (London: Arnold, 2000), 189-200Coyne 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
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 PsychiatryBritish Journal of PsychiatryThe British Journal of Psychiatry is a peer-reviewed medical journal published monthly by the Royal College of Psychiatrists containing original research, systematic reviews, commentaries on contentious articles, short reports, a comprehensive book review section, and a correspondence column...
- 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 NIMHNational Institute of Mental HealthThe National Institute of Mental Health is one of 27 institutes and centers that make up the National Institutes of Health...
and founding editor of the Schizophrenia BulletinSchizophrenia BulletinSchizophrenia Bulletin is a peer-reviewed medical journal which covers research relating to the etiology and treatment of schizophrenia. The journal is published bimonthly by Oxford University Press in association with the Maryland Psychiatric Research Center and Schizophrenia International...
) discussing the importance of David Healy's research in making true informed consentInformed consentInformed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
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)