In this Infomail, Dr. David Cohen, AHRP Secretary gives his brief personal impressions from the December 13 meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee preceded (Dec. 12) by two press briefings convened by AHRP and Woodymatters.com.
[Conflict of interest issues will be dealt with elsewhere.]
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I carefully read the two clinical reviews conducted and released by the FDA for this meeting, and I attended most of the meeting. I left thinking that I had watched a surrealistic play.
One highlight of the meeting for me was watching Tom Laughren, Director of the Division of Psychiatry Products of FDA’s Center for Drug Evaluation and Research, intently take notes and never look up as a long line of individuals made their 3-minute presentation to the committee, alternatively condemning and praising antidepressants (see summary below). Dr. Laughren never looked up even when Dr. David Healy charged him, on the public record, with being the sole author of an article in which suicidal events from drug-treated groups were arbitrarily switched to placebo-treated groups.
And when the committee members were given time to question the FDA officials about any aspect of the data they were given, or comment on any of the presentations they had just heard, no one picked up on Healy’s extraordinarily relevant charge.
I expected a committee member to ask, "Dr. Laughren, is Dr. Healy’s statement true? If so, can you tell us precisely how common occurrences of fake data are in the database the FDA is using to determine the risk of antidepressant-induced suicidality? If the FDA doesn’t have this information for us now, should we adjourn this meeting until it is provided to us?"
It seems to me that if the FDA took the suicidality issue seriously this time around, it would have asked some of the major independent critics and researchers, who have been discussing this issue for over 15 years, just how they would analyze the clinical trial data, what specific associations they would examine, etc. The FDA could of course have then proceeded to do exactly what it wished, but at least, even from a public relations point of view, it could have said that even naysayers had been consulted. This is after all a major analysis of nearly 400 trials with 100,000 patients, that requires very careful planning and comes after 15 years of FDA denial of the importance of the issue.
Yet I watched as FDA officials admitted not having asked drug manufacturers for specific adverse event data (such as akathisia and other instances of drug-induced activation, which the literature has long associated with sudden suicidality) for this review, or having arbitrarily decided to ignore any drug-withdrawal related data, or not having presented specific data bearing on the efficacy of antidepressants besides this single sentence: "Approximately 50% of subjects who received active drug and 40% of subjects who received placebo were designated as responders" (p. 31). Given that the entire scientific case for antidepressants rests on this 10% difference, a clear analysis of what factors in clinical trials might contribute to it–besides treatment–is definitely indicated in a report on risks of treatment that relies only on clinical trial data.
Although several committee members did ask some relevant questions, there was really no follow-up in spite of the FDA officials’ frequent admissions of "No, we didn’t ask for this data," or "No, we don’t have this data." There were a number of embarassing silences following these admissions, but never followed by "Why not?" It seemed as if all participants recognized the futility of the exercise but had agreed not to comment on this futility in public.
AHRP Press Conferences on December 12
On December 12, AHRP, in association with WoodyMatters.com, organized two press conferences, one at the National Press Club in Washington and the second at the Silver Springs Hilton in Maryland, at which public and media were briefed on the issues. Presentations were made by Kim Witczak and Eric Swann, and by Vera Hassner Sharav, Joseph Glenmullen, MD, David Healy, MD, John Abramson, MD, David Cohen, Ph.D, and Karen Barth Menzies, Esq. of the legal firm Baum Hedlund.
Kim Witczac and Eric Swann gave the personal perspective of the tragic suicide of Woody, a vibrant, healthy 37 year old man who was prescribed Zoloft for insomnia. His mental health deteriorated in ways later confirmed to be Zoloft-related in Pfizer documents. He committed suicide.
Vera Sharav compared antidepressants which had been marketed as "magic bullets" to "snake oil," noting the long list of indications for which the drugs were approved–despite lack of benefit–and the even longer list of indications for which they are being prescribed off-label. She questioned FDA’s truncated inclusion criteria for this analysis–to one day after ingesting the drug during the randomized phase. This contradicts good clinical practice and the FDA approved labels which stress the importance of monitoring during initiation and dose changes. She then noted the disparity between the UK analysis of the same trial data (2005) which reported 16 suicides and 177 attempts in 40,000 patients compared FDA’s report of 8 suicides and 133 attempts in 100,000 patients. She also questioned FDA’s claim that the data showed "no treatment effect" on suicides when the data shows: Suicidal Behavior by those on the drugs:
Age <25: RR = 2.30 (1.04 – 5.09)
Age 45 – 54: RR = 2.29 (0.73 – 7.14)
Age 45 – 64: RR = 1.75 (0.68 – 4.48)
Joseph Glenmullen, MD, gave a detailed historical review of a large number of previous signals in the literature concerning antidepressant-induced suicidality. He made the point that confusing it with "ordinary" suicidality is a false issue, as it can be easily recognized in connection with an activating syndrome (including mania and akathisia) that regularly accompanies it. He charged that the FDA has systematically swept the issue under the carpet since 1991, when it already possessed ample data to conclude that antidepressants are implicated. Glenmullen believes that fearing that warnings will scare patients is a bugaboo. He asked: if you had to make the decision to take or prescribe a drug, would you want to know the risk?
David Healy, MD, discussed how the effectiveness of antidepressants is misconstrued. He emphasized that data shows that only one in 10 patients taking antidepressants can be said to respond specifically to drug rather than to nonspecific and placebo factors. He showed how suicide-related events in several previous trials were arbitrarily switched from drug-treated to placebo-treated groups. He gave several examples of ghostwriting of clinical trial reports purporting to show efficacy and safety of antidepressants. He showed how data obtained from British drug regulators contradict the FDA-released data. Overall, Healy questioned the validity of the information typically used to draw conclusions about antidepressant-induced suicidality.
David Cohen, Ph.D., emphasized that clinical trials now used by the FDA to explore the link between antidepressants and subtle adverse events such as suicidality were completely unsuited for that purpose. I pointed out that these trials were only conducted by sponsors for the purpose of showing a tested drug’s superiority to placebo or equivalency to an existing drug, not to determine just how a drug might be psychologically influencing those who take it for weeks or months. I emphasized that if the FDA really wants to approve safe and efficacious psychotropic drugs, it needs to request from manufacturers studies that take as a starting point that these drugs are indeed psychotropic and have, by definition, complex and variable effects. More attention paid to creative methods to detect psychological and behavioral toxicity in Phase I studies is needed.
John Abramson, MD, gave an overview of the overwhelming penetration of industry influence and incentives inside what should be the most scientific and evidence-based forums of general and primary care practitioners. His slides showed the ubiquitous presence of drug industry advertising in every aspect and location of the annual convention of PCPs, including prominent drug ads at every registration desk, in the toilets, and even on the cards given to each doctor to record his or her attendance at courses for continuing education credits.
Karen Barth Menzies, partner in the lawfirm, Baum Hedlund, briefly reviewed the numerous instances of suppressed data on suicidality from various internal industry and FDA documents that were only made public because of litigation. She questioned the true purpose of holding the Advisory Committee at this late December date, with no expected vote for its members, and, given previous outcomes, expressed some pessimism.
Key Points of Public Speakers at December 13 FDA Advisory Committee Meeting
The following are my brief notes summarizing what I understood as the key points made by almost every speaker who testified for 3 minutes during the public portion of the December 13 meeting.
– Julie Totten represented Families for Depression Awareness. She said that families often don’t know how to accompany people who suffer from depression, and she promoted her group’s Depression Wellness Guide.
– Suzanne Gonzalez spoke of losing her husband who committed suicide at age 40 while on Paxil.
– John Mann, professor of psychiatry, emphasized the negative consequences of depression, especially suicide.
– Allen Jones, whistleblower and formerly on AHRPs’ Board of Directors, highlighted rampant conflicts of interests at the FDA and in its advisory committees, including this one.
– Nick Korzie, 16 years old, spoke of his experience as a depressed teenager prescribed psychiatric drugs. "I was given antipsychotics though I wasn’t psychotic, I was given anti-seizure drugs though I’ve never had seizures." He ended with: "We, are the people. You, the FDA, should protect the people."
– Christopher Kratochvil, a psychiatrist and clinical trial researcher, spoke on behalf of the American Academy of Child and Adolescent Psychiatry. I missed most of his talk.
– Darrel Regier, director of research at the American Psychiatric Association, said that the FDA database is limited because clinical trials don’t evaluate suicidality; only prospective trials can do so. He asked the committee to provide realistic guidelines, stating that some doctors refuse to initiate antidepressant treatment because they can’t guarantee 7 visits in 12 weeks for patient monitoring, as the latest FDA advisory indicated.
– Moira Doilan spoke for the Medical Accountability Network. She deplored that the FDA only used a single suicidal event per subject in its analysis and let the manufacturers decide what constituted such events. She asked that warnings of the possibility of antidepressant drug-emergent suicidality be quickly publicized by the FDA.
– Ashir Gruder spoke of his father who killed himself 13 days after being prescribed Paxil.
– Deborah Gruder spoke of her husband and Ashir’s father, who loved life and whose suicide was completely unexpected. She shouted to committee members that antidepressant-induced suicides were "nothing but a blood bath and mass murder."
– Gwen Olsen spoke of her 20 year-old niece on antidepressants who self-immolated immediately after failing to hang herself. Olsen used to work as a pharmaceutical representative and discussed how she was trained to persuade doctors to prescribe drugs.
– Beverly Hatcher spoke of her mother with no history of depression who killed herself after 16 days on Paxil.
– Ellen Liversidge, a member of AHRP, spoke of her son who was put on Zyprexa and gained 100 lbs, then fell into a coma and died.
– Lisa Van Syckel spoke of her 15 year-old daughter who attempted suicide while on Paxil.
– Paula Clayton, psychiatrist, spoke for the American Foundation for Suicide Prevention. She’s prescribed antidepressants since 1958. She urged the committee not to issue a black box warning.
– Diane Dorlester spoke for the National Mental Health Association. She described her positive experience on antidepressants and asked the committee not to restrict access to these drugs.
– Lewis Kopolow, President of the Maryland Psychiatric Association, stated that depression is a disease, that it affects physical health, and that half of depressed people don’t get help.
– Joseph Glenmullen, psychiatrist at Harvard Student Health service, said that the FDA never did the promised gold standard study on suicidality and has swept the problem under the carpet for 15 years. He said that drug-induced suicidality was a distinct, easy-to-recognize phenomenon.
– Dan Reidenberg, director of the National Council for Suicide Prevention, urged the FDA not to make it difficult to get life saving antidepressants.
– Karen Menzies, lawyer, expressed astonishment that the FDA did not look at adverse effects, especially akathisia, in connection with sucidality. She stated that data were regularly hidden by the drug companies, and had provided examples to the committee. She urged the committee to use its legal powers to ask for this data, but deplored that "You just don’t!"
– Michelle Moore spoke of her husband who was "murdered." He committed suicide 1 day after being switched to Paxil from 30 days of Prozac. He was not depressed and had given no clue.
– Tony Noll, whose father committed suicide on an antidepressant, said "I came to speak to you on behalf of the statistically insignificant."
– Mary Margaret Neill spoke of her five depressive episodes and the multiple medication regimen she has been on, and that her current one is working.
– Donna Barnes spoke for the National Organization for People of Color against suicide. She stated that Blacks use relatively less psychiatric treatment, and comply less. She urged the FDA not to put a black box warning.
– Sarah Bostock’s daughter Cecily killed herself on Paxil. Bostock has set up SSRIstories.com, where over 1200 media stories on SSRI induced violence and suicide since 1998 are compiled and analyzed. She invited committee members to view this database.
– Kim Witczak’s husband Woody committed suicide after being prescribed Zoloft for insomnia. Witczak said Woody loved life and had no serious personal problems. She described in layperson’s terms what seemed like a sudden preceding episode of akathisia. WoodyMatters.com publicizes his story and the issues.
– Joseph Weiner, psychiatrist at Long Island University Medical Center, disclosed financial support for his testimony from the American Psychiatric Association. He described his "personal victory over major depression due in large part to antidepressant treatment. If only I’d received antidepressants earlier, I would have avoided years of excruciating suffering."
– Angela Heck described the fear and ongoing bewildering consequences of an episode when her husband, in an antidepressant-induced dissociative episode, tried to kill her with a knife.
– Sheila Matthews spoke for Able Child. She emphasized the subjectivity of psychiatric diagnosis, then gave results of two surveys her group commissioned on public knowledge of Medwatch, the FDA’s spontaneous adverse drug reaction reporting system. She asked to FDA to set up public campaigns to let consumers know where/how to report ADRs, as consumers detect effects sooner than providers.
– Robert Carolla spoke for National Alliance on Mental Illness. He described frustrating talk therapy in pre-drug days, his medication experiences and his long road to recovery. Suicidality is frequent and subtle, he said. He asked the FDA not to discourage people from taking antidepressants.
– Erin Crowley spoke for the National Coalition for Drug Awareness. I missed most of her talk.
– Andy Vickery, lawyer, said that controlled trials are not designed to evaluate suicidality. He asked why the FDA abandoned its own algorithm for determining causality in individual cases of drug reactions. He asked why is this committee meeting if it’s not asked to vote on anything?
– John R. Hayes spoke for Eli Lilly and Company. He urged the panel to be rational.
– Heidi Bryan, speaking on behalf of the Feeling Blue Suicide Prevention Council, described how antidepressants saved her life.
– Donald Farber, lawyer, urged committee members to be honest. He said that the committee was not meeting to decide who should get what treatment, but first and foremost to decide on the most accurate description of the risk of antidepressant-induced suicidality.
– David Healy, psychiatrist and researcher, presented slides showing how drug companies routinely alter data, switching suicide-related events from drug-treated groups to placebo groups, and charged that Thomas Laughren himself, in a single-authored article, did the exact same thing.
– Luis Fuller [spelling?] spoke for Citizens’ Commission on Human Rights. He presented Oregon data showing increases in suicide attempts positively associated with antidepressant treatment. He stated that ER visits from antidepressant-induced suicidality are more frequent than all similar events from heroin, cocaine, methamphetamine, and other illicit drugs combined.
– Carolyn Rabinowitz, a child and adolescent psychiatrist, emphasized that depression hurts a lot and that drugs help.
– Sheri Walton says she has major depression, that it went untreated and undiagnosed for 20 years and ruined her life, and that antidepressants saved her and gave her back her life. She believes that unecessary warnings may scare people away from treatment.
– Jane Richner spoke of her 20 year-old son who was given a 90-day prescription of Celexa for situational anxiety during a 10-minute medical visit. Life was all coming together for him, but he hung himself. He manifested definite akathisia beforehand. She emphasized the importance of drug-induced fatal withdrawal effects.
– Nancy Sharby described a long family history of suicide, and she and her children have been diagnosed with mood disorders. She emphasized the burden of depression.
– Vera Hassner Sharav, president of AHRP, highlighted numerous flaws in the FDA clinical review’s approach and analysis, and pointed out major discrepancies with British studies of similar data. [Her full presentation is available on this website.]
– Kendrick Moxon, lawyer for Citizens’ Commission on Human Rights, described how completely conflicted the FDA’s advisory committees were, especially the 1991 committee that ruled against warning about SSRI-induced suicidality.
– David Shern of Mental Health America argued that the availability of SSRIs has led to a decrease in suicide rates. He stated that a black box warning won’t promote a public health agenda.
– Alison Malmon of Active Minds, Inc., spoke of the large unmet need for help and support among depressed and distressed youths in high school and college.
– Ann Blake Tracy spoke on behalf of International Coalition for Drug Awareness. She emphasized the harm that widespread use of SSRIs has produced for two decades.
– Eric Caine, professor of psychiatry and president of Suicide Prevention Action Network acknowledged some funding from drug industry. He urged FDA not to scare people away from care.
– Rosemary Dorsett spoke of how her son got screened for depression during his physical, got Prozac from his GP, quickly became insomniac, lost weight, heard voices, and shot himself in chest. She emphasized how he loved life and this was totally out of character.
– Mary Ellen Whitter spoke of her daughter who loved life, her life, and people, and was happy and extremely functional. After graduation, she became insomniac and anxious, received Paxil. Immediately worsened across the board, and hung herself after 7 days on drugs.
– Nada Stotland, physician and with Mental Health America, stated that antidepressants save lives and the risk of a back box warning is that patients will be frightened to take them.
– Roger Peele, psychiatrist, spoke of his long family history of suicide and argued that suicides are depression-related, not drug-related.
– Eric Swann, brother in law of Woody Whitczak who killed himself on antidepressants, urged the committee to do the right thing and recommend a back box warning for adult suicidality.
– Dawn Jeronowitz described how she was diagnosed with anxiety as no physical cause for pain in her finger was detected, and was prescribed Paxil. She experienced outright mania, which she described in harrowing detail. She asked how such dangerous drugs could be legally pushed on people without any information provided on their major adverse effects.
– Allen Routhier said his was given an "unmarked free sample of Wellbutrin" by her doctor and was dead within one week. He said this meeting was a circus side show, with the real action being the unfettered sale of dangerous drugs for corporate profits. He said he was at such meetings three times now, with nothing ever getting done. He wondered if new Nuremberg trials were needed.
– Ann Sheffield spoke of her three books on the negative impact of depression. She said: "I’d be dead if it weren’t for antidepressants."
– Laurie Yorke spoke of Paxilprogress.org, a website which offers peer support for people undergoing withdrawal from antidepressants.
– Hanna Stotland, a lawyer, said that she was crippled by depression, and drugs saved her life and allowed her to have a productive career. "Untreated depression is the danger we need to fear most."
– Charles Reynolds, psychiatrist, spoke for the American Association of Geriatric Psychiatry. I missed most of his talk.
– Peter Breggin, psychiatrist, told the committee "The data you’re looking at is junk!" He said drug companies routinely hide damaging data, and that as expert in numerous cases of drug-induced damage, he’s seen "innumerable" instances that have never made it to the FDA or publications, examples of which he’s provided to the committee.
– Robert Gibbons, Center for Health Statistics at University of Illinois at Chicago, stated that data from Netherlands show that drop in prescriptions of SSRIs are associated with increases in youth suicide rates.
– Carl Salzman, psychiatrist, spoke for the American College of Neuropsychopharmacology. He said he was concerned about unintended consequences of a black box warning.
– Derek Braslow, lawyer, stated that data relied upon by the FDA isn’t reliable. "The science is here, in the people."
– Robert Valuck of the University of Colorado argued with supporting slides that fewer prescriptions of antidepressants would definitely result from a black box warning.
– Steven Davis, physician, believed that as a result of a black box warning, physicians will be scared to prescribe antidepressants.
Dr. David Cohen
(305) 348-4599
Contact: Vera Hassner Sharav
212-595-8974