Antidepressants and Violence: Problems at the Interface of Medicine and Law_PLoS

Critics have argued that second generation antidepressants—the SSRIs and SNRIs—are hugely over prescribed in large part due to physician (and public) ignorance about their potentially lethal side effects.  

The issue was at the center of the defense argument in the Christopher Pittman murder trial. Christopher was tried as an adult though he was 12 years old when he killed his grandparents while under the influence of the antidepressant Zoloft. South Carolina law allowed an “either or” verdict only. The jury found him guilty. However, the state’s draconian legal inflexibility was widely criticized. Judge Daniel Pieper, who presided over that trial, was clearly perplexed about the issues raised by this case.

At the trial’s end, Judge Pieper stated:  
“There is no case in South Carolina that addresses involuntary intoxication by prescription drugs…It seems to turn the whole medical system on its side if you can’t rely on the medication your doctor prescribes. It could potentially force you into a situation of lifetime commitment if that drug induces an effect of which you’re not aware…There’s something disconcerting about that, albeit probably something of a legal nature that is troubling me” [1].

Christopher was granted an appeal before the South Carolina Supreme Court scheduled for early October.

The public is largely unaware that adverse effects from prescription drugs kill more people than illicit drugs ever have. But you would never know that by reading the medical literature which is under the tightly controlled influence of drug manufacturers and their communications management firms who pay influential academic scientists to pen their name to prepared, ghost written articles purportedly analyzing clinical trial data. The most recent academic to blow the whistle on the deceptive practice of promoting products under the guise of science in peer reviewed journals, is Dr. Aubrey Blumsohn, formerly of Sheffield University (UK). [2] The problem rests, in part, with journal editors who have been tacitly complicit in undermining the integrity of the scientific literature. By failing to ensure that peer review is not biased; by failing to publish critical analyses by independent authors, fearing (one suspects) possible loss of corporate reprint income; and by failing to retract articles whose claimed findings are belied by the evidence; journals have perpetuated fraud.  

“Antidepressants and Violence: Problems at the Interface of Medicine and Law,”  by Drs. David Healy, Andrew Herxheimer, and David B. Menkes published in PLoS Medicine, lifts the lid on the most explosive aspect of these drugs’ dangerous effects—namely; violent, even homicidal behavior.  http://medicine.plosjournals.org/archive/1549-1676/3/9/pdf/10.1371_journal.pmed.0030372-L.pdf  [3]

This is a scientific review of evidence found in (1) the premarketing controlled clinical trial data submitted by manufacturers to regulatory agencies (MHRA in the UK and FDA in the US); (2) data from the UK Drug Safety Research Unit (DSRU); (3) reports from 1,374 viewers who responded by e-mail after a BBC Panorama broadcast in 2003; and (4) evidence from specific medico-legal cases involving homicide.

“Our main finding,” the authors state, “is that unselected sets of placebo-controlled trials of antidepressants show evidence for an increased relative risk of aggressive behaviours on treatment, although such outcomes apply to only a small subset of patients.”

Manufacturers, with support from high ranking regulatory agency officials, have for years denied evidence of drug-related risks of harm, and downplayed the significance of a unique adverse drug effect profile of second generation psychotropic drugs. In contrast to the older tricyclic antidepressants, SSRIs induce akathisia, emotional disinhibition, emotional blunting, and manic or psychotic reactions. The authors suggest that it is these drugs’ recognized mechanisms of action—not an underlying condition—that may trigger violence: “There is good evidence that antidepressant treatment can induce problems such as these and a prima facie case that akathisia, emotional blunting, and manic or psychotic reactions might lead to violence.”

The signs of violence and suicidality were there since the first SSRI antidepressant, Prozac (fluoxetine) was tested in premarketing trials.

Indeed, in May 1984, Germany’s regulatory agency (GBA) rejected Prozac as “totally unsuitable for treating depression.” [4] 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. [5] 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.” [6]

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.” [p. 6] 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—a known irreversible side-effect of neuroleptics.

“Nervousness,” Dr. Kapit wrote, “was the most common adverse symptom cited by long-term fluoxetine patients who eventually discontinued the drug.” He pointed out that “depressed patients often suffer from insomnia, nervousness, anorexia and weight loss” the drug’s propensity to induce these same symptoms “may possibly exacerbate” their illness. Germany’s regulatory agency, BGA, did not approve Prozac until 1989, when Lilly agreed to add a warning in the drug’s label in Germany. 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.

Internal documents show that the FDA and MHRA have, through selective data analyses, buried the most serious, clinically significant, adverse drug effects. To minimize such bias, Drs. Healy, Hexheimer, and Menkes analyze the complete paroxetine (Paxil) data set submitted by GlaxoSmithKline to the UK Committee on Safety and Medicine, including comparison trials involving other SSRIs. They also analyzed the complete data set on pediatric sertraline (Zoloft) trials submitted by Pfizer.  “The use of this dataset thus involves no selection by the authors, and any selection bias there might have been on the part of the company seems unlikely to have increased the size of the problem.”

In the trials posted on the GSK website, the authors note, “hostile events are found to excess in both adults and children on paroxetine compared with placebo, and are found across indications, and both on therapy and during withdrawal. The rates were highest in children with obsessive compulsive disorder (OCD), where the odds ratio of a hostile event was 17 times greater (95% confidence interval [CI], 2.22–130.0).”

The authors suggest that, perhaps the most significant evidence for drug-induced violence probably comes from healthy volunteer studies: hostile events occurred in three of 271 (1.1%) volunteers taking paroxetine, compared with zero in 138 taking placebo. “Although not statistically significant, this finding is striking because hostile events are unusual in healthy volunteer trials, and this figure was higher than the rate reported in clinical populations above.”

Pfizer’s data from the pediatric Zoloft trials shows that “aggression was the joint commonest cause for discontinuation from the two sertraline placebo-controlled trials in depressed children. In these trials, eight of 189 patients randomised to sertraline discontinued for aggression, agitation, or hyperkinesis (a coding term for akathisia), compared with no dropouts for these reasons in 184 patients on placebo (95% Confidence Interval, 1.72–infinity). There were 15 discontinuations on Zoloft compared with two on placebo in any treatment induced manifestation of activation (i.e., suicidal ideation or attempts, aggression, agitation, hyperkinesis, or aggravated depression), a relative risk of 7.3 (95% CI, 1.70–31.5; p = 0.0015). The published report failed to include this data in the analysis. [7]

“In the only other placebo-controlled sertraline paediatric trial, undertaken in children and adolescents with OCD, there were ten dropouts out of 92 patients on  sertraline, five of whom discontinued for behavioural activation, two for agitation, one for aggression, one for nervousness, and one for emotional lability. In comparison, there was one discontinuation for hyperkinesis out of a total of two dropouts from 95 patients on placebo.” However, the published report failed to report these data. [8]

Failure to report these data in published reports is prima facie evidence of journal failure as scientific gatekeepers: peer review as currently practiced results in biased reports and concealment of negative data. New York State Attorney General, Elliott Spitzer, correctly termed this practice, fraud.

By 2003, the UK MHRA received 121 cases of aggression on paroxetine, and by January 2006 that number had risen to 211. [9] The authors note, that estimates for such physician adverse drug effect reporting systems range between 1% and 10% of actual adverse effects on treatment.

Drug-induced violence is not an academic issue, nor can it be set aside as “anecdotal:”  drug-induced violence poses a threat to unsuspecting consumers and the community.

A new website has been launched providing ready public access to more than 1,000 news reports, mainly criminal in nature, that have appeared in the media or that were part of testimonies before FDA advisory committee meetings in 1991 or 2004. See: http:// www.ssristories.com

The website creators, Rosie Meysenburg (gm1000@prodigy.net ) and Sara Bostock (sara.bostock@comcast.net) note: “Even these 1000 documented stories only represent the tip of an iceberg since most stories do not make it into the media.”

Below is the latest “story” from Free Press involving a former pharmaceutical  sales rep who is blowing the whistle on the hazards of psychotropic drugs in her book, Confessions of an Rx Drug Pusher.  Her own niece set herself on fire after inability to get off an antidepressant.

References
1. (2005) State of South Carolina v. Christopher Frank Pittman. Case Number 04-GS-12-571. Trial transcript. pp. 2467– 2468.

2. Dr. Aubrey Blumsohn, blew the whistle on collusion between Proctor & Gamble and the University of Sheffield to conceal the trial data from P & G’s osteoporosis drug, Actonel. See: http://www.scientific-misconduct.blogspot.com .

3. Healy D, Herxheimer A, Menkes DB (2006) Antidepressants and violence: Problems at the interface of medicine and law. PLoS Med 3(9): e372: http://medicine.plosjournals.org/perlserv?request=get-document&doi=10.1371/journal.pmed.0030372 .

4. Internal documents uncovered during Prozac litigation, Fentress v Eli Lilly, PZ 281-1524 Bad Homburg (May 25, 1984).

5.Eli Lilly internal analysis submitted to the Joachim Wernicke (July 2, 1985), PZ 2441 2000. Document uncovered during Fentress litigation.

6. Kapit R. FDA Safety Review NDA 18-963, March 23, 1985.

7. Wagner KD, Ambrosini P, Rynn M, Wohlberg C, Yang R, et al. (2003) Effi cacy of sertraline in   the treatment of children and adolescents with major depressive disorder: Two randomized controlled trials. JAMA 290: 1033–1041.

8.  March JS, Biederman J, Wolkow R, Safferman A, Mardekian J, et al. (1998) Sertraline in children and adolescents with OCD: A multicenter randomized controlled trial. JAMA 280: 1752–1758.

9. Medicines and Healthcare Products Regulatory Agency (2006) Adverse drug reactions online information tracking: Drug analysis print. Available at: http://www.mhra.gov.uk/home/groups/public/documents/sentineldocuments/dap_1130236020641.pdf .

Contact: Vera Hassner Sharav
veracare@ahrp.org

~~~~~~~~~~~~~~

http://lfpress.ca/newsstand/Today/Books/2006/09/11/1825001-sun.html
FREE PRESS
Former drug rep has horror stories to tell
Mon, September 11, 2006
By KATHY RUMLESKI <mailto:krumleski@lfpress.com> ,

Calling her book and North American tour a child-advocacy campaign, Gwen Olsen is warning parents of the dangers of some antidepressants and psychotropic drugs.

After spending 15 years in the pharmaceutical industry, selling some of the drugs she now says can be deadly, Olsen has blown the whistle on her old employers and published Confessions of an Rx Drug Pusher: God’s Call to Loving Arms.
"I had a moral responsibility to tell people everything I knew," she said in a phone interview from her home in Texas.

What Olsen knows is horrendous.
Olsen’s niece set herself on fire and died after being on an antidepressant.
"She burned herself alive. She said . . . ‘I’d rather be dead than feel crazy like I feel on those drugs.’

The niece was prescribed medication following a car accident. She had problems when she stopped taking the drug.  "She got addicted and when she tried to withdraw she became depressed," Olsen said. Her doctor prescribed her an antidepressant and that sent her spiralling downward, leading to suicide.

Olsen was also treated for depression in 1992 with Zoloft. "I became manic psychotic. About 25 per cent of the population will have a serious adverse reaction. I was educated about these side effects and I had sold drugs that caused these side effects."

Olsen walked away from her job and her career in 2000 when her bosses asked her to sell the antidepressant Celexa.  In clinical studies, this medication had increased the risk of suicidal thinking and behavior in children and adolescents who had depression and other psychiatric disorders.

Olsen said children are more vulnerable to the side effects of these medications because of their developing organs.  "They are three times as likely to react to these drugs as an adult is."  Olsen said there is "rampant economic incentive to over-prescribe drugs. "This is a social control mechanism."

Psychotropic drugs were a big part of Canada’s $24.8 billion pharmaceutical industry in 2005. In the U.S. $3.3 billion was spent on drugs to treat attention-deficit hyperactivity disorder.

Olsen said kids diagnosed with ADHD may be helped with natural treatments. She suggested parents try getting more Omega-3 essential fatty acids, such as flax, krill or fish oil, into their children’s diet and eliminate refined carbohydrates and aspartame.

Olsen has another dire warning for parents. Once someone gets started on these mental-illness drugs, he or she may never get off them. "It’s a lifelong customer for the pharmaceutical industry. They alter the pathology of brain chemistry so you can’t get off them. They’re extremely addictive."

Presentation and book signing on Sept. 23 at Western Lamplighter Inn on Wellington Road. Tickets for the two-hour event, beginning at 10 a.m., are $15 in advance or $20 at the door. Call 519-673-1132 for more information or tickets.

FAIR USE NOTICE: This may contain copyrighted (© ) material the use of which has not always been specifically authorized by the copyright owner. Such material is made available for educational purposes, to advance understanding of human rights, democracy, scientific, moral, ethical, and social justice issues, etc. It is believed that this constitutes a ‘fair use’ of any such copyrighted material as provided for in Title 17 U.S.C. section 107 of the US Copyright Law. This material is distributed without profit.