October 26

Debate Over Antidepressants: FDA role in suppressing damaging data – WSJ

WSJ: Debate Over Antidepressants: FDA role in suppressing damaging data

Tue, 25 May 2004

How were drug manufacturers able to conceal vital evidence of harmful antidepressant drug effects? The answer is becoming clearer by the day: federal regulators and the psychiatrists who tested these drugs in clinical trials are invested in promoting industry’s products. They have turned a blind eye to disturbing evidence of harm, lest such information affect drug marketing goals.

A front page article in The WALL STREET JOURNAL (excerpt below) examines FDA behind-the scenes strong-arm bully tactics. A flurry of e-mail messages beginning December 2003, reveal that senior FDA officials muzzled Dr. Andrew Mosholder, a highly regarded drug safety analyst at the FDA who is a psychiatrist experienced in treating children and adolescents. Dr. Mosholder’s analysis of the SSRI antidepressant trials in children and adolescents, led him to agree with British regulators: the drugs posed too high a risk for children without a demonstrable benefit to justify the risk. Warnings should be issued at once. Dr. Mosholder’s conclusion has been corroborated by several independent analysts, most recently by two meta-analyses published in April in major international medical journals.
See: link to April 23 report by Craig Whittington and colleagues and an accompanying editorial in the Lancet
See: April 10 report by Jon N Jureidini and colleagues in the British Medical Journal

FDA officials who suppressed Dr. Mosholder’s report, and prevented him from presenting his analysis and recommendations at the FDA advisory committee (February 2) are: Dr. Robert Temple, associate director for medical policy in the FDA’s drug-evaluation center, a 32-year veteran of the FDA; Dr. Thomas Laughren, chief of FDA’s psychiatric drug review team who is with the agency 17 years, and has overseen the approval of many of the antidepressants at issue; and Anne Trontell, deputy director of the drug-safety office. These officials bear substantial responsibility for putting children’s lives at risk by allowing the risks to be concealed from prescribing physicians and families. A warning of the potentially hazardous effects to prescribing physicians may have prevented tragic loss of life.

The NEW YORK TIMES reports about the reality of severe SSRI drug withdrawal symptoms affecting a substantial number of patients who want to stop taking drugs. Not until October, 2002, when the BBC Panorama program exposed the severity of paroxetine (Paxil) withdrawal symptoms drug companies and their consulting psychiatrists, and the FDA denied the problem existed. After the British Medicines authority banned Paxil for children on June 10, GlaxoSmithKline changed the UK drug label (June 25), disclosing an overnight 50-fold increased risk of withdrawal symptoms–from 0.2% to 25%. See: Charles Medawar and Anita Hardon, Medicine Out of Control? Asknat, 2004, p. 205. See also: How to Stop Depression Medications: Very Slowly by Mary Duenwald, NY Times,C-1

The FDA defines health fraud as “the promotion, for profit, of a medical remedy known to be false or unproven.” See: http://www.quackwatch.org/01QuackeryRelatedTopics/quackdef.html

Antidepressant drug manufacturers and leading psychiatrists who tested the drugs have known that the drugs failed consistently to demonstrate a therapeutic benefit for children, and they knew that some children exposed to these drugs suffered severe adverse effects—including severe withdrawal symptoms and a risk of suicidal behavior. Those involved in the promotion for profit, of SSRI antidepressant drugs for children–despite that knowledge–should be investigated for fraud.

The two major analyses of the antidepressant pediatric trials, published in The Lancet and BMJ are nothing less than an indictment of the US psychiatric establishment. These reports demonstrate beyond reasonable doubt that the published US journal articles claiming that SSRIs are “safe and effective” for children, are contradicted by the evidence. The Lancet analysis demonstrates that leading US psychiatrists whose names are penned to those published reports, had failed to analyze the complete clinical trial data-or, if they did, they had concealed the negative results from their published reports.

However, those discredited reports lent the appearance of credibility to industry’s false assurances about the safety and effectiveness of SSRIs for children. The psychiatrists who authored those published journal reports aided industry in “the promotion, for profit, of a medical remedy known to be false or unproven.”

Those discredited reports influenced psychiatrists and pediatricians into prescribing SSRI antidepressants widely for children. As demonstrated by the MEDCO Drug Trend report, increased prescribing of SSRIs for children resulted in windfall profits for drug manufacturers. Their collaborating psychiatrists and institutions also reaped financial benefits. But increased prescribing exposed an increasing number of children to increased risk–some of these children committed suicide.

Three reports this month focus on the huge increase in SSRI antidepressant prescriptions issued for American children: they are, the Medco Drug Trend report, a parent opinion poll, an SSRI prescribing report sponsored by NARSAD.

Additionally, an authoritative fourth report by the US Preventive Treatment Services (USPTS, released May 18) found that “screening for suicide” programs which have been recommended by the psychiatric establishment as an unacknowledged device for expanding the antidepression drug market, have failed to demonstrate any value in reducing suicide or mortality.
See: USPTS Task Force Ratings: Strength of Recommendations and Quality of Evidence. Guide to Clinical Preventive Services, Third Edition: Periodic Updates, 2000-2003.
See also: Annals of Internal Medicine, May 18.

1. The MEDCO Drug Trend report documents the skyrocketing increase in SSRI prescriptions for children. However, evidence of a medical need to justify that increase is nonexistent.

  • Prescription drug spending for behavioral conditions rose 77% between 2000 and 2003;
  • In 2003, spending on behavioral medications to treat children overtook both the antibiotic and asthma categories, which are traditionally high-use categories in pediatric medicine;
  • Among the largest increases were medications primarily used to treat ADHD — where spending increased by 183% for children overall–and by 369% increase for children under age 5;
  • Spending on antidepressants for children grew 25%, while use of these drugs rose 27 percent between 2000 and 2003;
  • In the first three months of 2003, the number of children using antidepressants increased by 15%;
  • The number of children on drugs to treat autism and conduct disorders increased by more than 60% from 2000 to 2003, while spending on these drugs rose 142% in the pediatric group;
  • Among children ages 5 through 9, drug use was up 85 percent, while spending in this category grew 174%;
  • Use of antibiotics in children showed no change, while spending (i.e. cost) increased 24%.

See: Medco’s Drug Trend Report and Symposium: http://www.drugtrend.com

The most severe, immediate harm from antidepressants affects a small minority of children. The full range of damage these drugs may cause to the developing brain of millions of American children will likely emerge only years later. For the present, the psychiatric drug stakeholders are formulating novel “interpretations” of the data through their prism of self-interest.

For example, Laurie Flynn, former executive director of NAMI (National Alliance for the Mentally Ill), who now heads Carmel Hill Center for Early Diagnosis & Treatment–a division of Columbia University, Child & Adolescent Psychiatry–a federally funded, national teenage mental health screening program, claimed that the MEDCO report demonstrates the importance of antidepressants: “just like antibiotics and anti-asthma drugs.”

2. A summary report about a telephone poll conducted “amidst the current controversy over anti-depressant safety” during the first week of May, was released by Carmel Hill. The poll was commissioned by Columbia University–a major stakeholder in psychiatric drug research with substantial financial support from the drug industry and government. 512 parents of children under 18 were polled by phone. The questions parents were asked appear to have been designed to elicit responses favoring widespread school “screening for depression” to prevent suicide.

The most robust findings reported by Carmel Hill show that:

  • 68% of parents (78% males, 57% females) believe that antidepressants are overprescribed to teens compared to 8% who think the opposite!
  • 67% of parents (73% male, 60% female) believe antidepressants are usually, but not always safe for teenagers.
  • More than half the parents believe that antidepressants pose an increased risk of suicide;
  • 38% of parents say the drugs affect brain development;
  • 37% of parents believe they cause weight gain / loss; and
  • 30% of parents (46% female, 22% male) believe antidepressants worsened depression. See: www.teenscreen.org

The results are being spun to justify increased screening which the authoritative USPTS found useless. However, the unacknowledged purpose of screening is increased treatment–i.e. increased use of antidepressants.

3. A report funded by NARSAD (the National Alliance for Research in Schizophrenia and Depression) was presented at the American Psychiatric Association (May 1-6. 2004). It demonstrates how selective reporting and novel interpretations blur the facts to deflect their impact. The indefensible antidepressant prescribing increase in children is disingenuously downplayed. Indeed, the NARSAD-sponsored report by Linda Robinson omitted any mention of the most astounding evidence–that the highest rise in SSRI prescriptions–369%–was for preschool age children. (See: abstract NR485)

NARSAD is financially dependent largely upon psychotropic drug manufacturers – as is NAMI.

The bias of the NARSAD-sponsored report is further underscored by the author’s misrepresentation of the definitive evidence of drug-induced suicidality.

Disclosure of that evidence has raised public concern and shaken the public trust.

Robinson is quoted on Doctor’s Guide (below) stating: “Recently and notably there has been some British research leading to concern about suicidality among children using SSRIs,” Ms. Robinson added. “We haven’t seen that problem here in U.S. research, but the issue is currently under review by the U.S. FDA.”

See: APA: Depression Diagnosis Rate Rising Among US Children Along With SSRI Use By Bruce Sylvester. Doctor’s Guide

The evidence linking SSRIs to suicidality is NOT merely suggested by “some British research”–the evidence has been scientifically demonstrated and replicated by several authoritative, independent analysts–including FDA’s expert drug safety analyst.

Indeed, in April 2004, the suicidal risk has been acknowledged by manufacturers* of antidepressants in their revised labels See, for example: http://www.effexorxr.com/pdf/Wyeth_HCP.pdf http://www.wyeth.com/contentShowLabelling.asp?id=100

*Pfizer and Lilly have yet to revise the labels of their antidepressants (sertraline / Zoloft; fluoxetine /Prozac; atomoxetine / Strattera)

Thus, it would appear that the purpose of trivializing the evidence about drug hazards are calculated to encourage prescribing physicians not to hesitate, but to continue to prescribe the drugs for children as if they were “safe and effective.”

For years, the psychiatric drug industry and those who are financially dependent on that industry’s profitability, have blocked independent examination of the full evidence, dismissing psychiatric drug casualties as “anecdotal,” not representative of a problem. These same stakeholders are now engaged in spinning the damaging data, raising spurious doubts about the credibility of company controlled clinical trial data. The purpose is to delay action by the FDA, and thereby to prolong the reckless drug prescribing binge that MEDCO documented.

Contact: Vera Hassner Sharav
Tel: 212-595-8974



In Debate Over Antidepressants, FDA Weighed Risk of False Alarm Doubting Data on Suicide And Kids, Officials Stopped Presentation by Staffer Avoiding a ‘Shouting Match’


May 25, 2004; Page A1

WASHINGTON — Last December, drug-safety analyst Andrew Mosholder delivered a blunt message to his colleagues at the Food and Drug Administration: Young people taking antidepressants were more likely to become suicidal.

That conclusion, based on Dr. Mosholder’s analysis of clinical trials comparing youths who took the drugs with those who took a placebo, set off a still-raging debate over whether the benefits of antidepressants outweigh the risks for children and teens. It’s a question of keen interest for the pharmaceutical industry and for American families, since the drugs are prescribed to millions of young people.

Dr. Mosholder’s bosses criticized his findings as premature and based on unreliable data. They barred him from reporting his conclusion to an FDA advisory committee that met in February. Above all, they didn’t want to drive people away from the medications “when we weren’t sure that was the right thing to do, and it may be the wrong thing to do,” says Robert Temple, associate director for medical policy in the FDA’s drug-evaluation center.

The clash illustrates the FDA’s challenge in balancing the need for prompt warnings about potential side effects from drugs against the risk of discouraging the use of helpful medicine. Although critics have accused the FDA of a cover-up to protect a lucrative market for drug makers, the events suggest a more complex situation, in which the agency took the initiative in uncovering much of the data but hesitated to make a declaration that was sure to alarm many patients and doctors.

Antidepressants and suicide are particularly tough to analyze because it’s hard to tease out whether suicide is a side effect or a consequence of depression itself. Even defining a “suicidal event” — crucial to figuring out whether an antidepressant induces suicidal behavior — is subjective.

In a rare glimpse of the FDA’s struggle, a series of internal e-mails reviewed by The Wall Street Journal shows how one of Dr. Mosholder’s superiors was worried he would condemn the drugs too strongly before the advisory committee. Unlike most FDA deliberations, the committee meetings are public. The superior, Anne Trontell, deputy director of the drug-safety office, sent Dr. Mosholder a list of questions for which she wanted him to prepare and advised him “to acknowledge the limitations of your analyses.” She also offered to “provide guidance on how to finesse the likelihood of a shouting match at the table.”

The FDA’s handling of Dr. Mosholder’s conclusions is drawing fire from Capitol Hill, and committees in both the House and Senate are investigating. “You don’t just ask someone to clam up,” says Iowa Republican Charles Grassley, chairman of the Senate Finance Committee. “If there’s any doubt, they ought to put out the caution to the public at large, not try to muzzle it.”

Mr. Grassley says his investigators are looking at other possible instances where FDA drug safety officials weren’t allowed to make their conclusions public. The investigators are interviewing Dr. Mosholder, who has hired a lawyer.

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