Twenty-two years after the US marketing of Prozac, which changed the marketing, prescribing and widespread consumption of psychoactive drugs–a meta-analysis of six large studies published in the Journal of the Medical Association (JAMA) confirms that industry’s blockbuster drugs, SSRI antidepressants were unable to outperform placebos for moderate symptoms of depression. Just like the older, much cheaper tricyclic antidepressants, SSRIs show a clinical value only for severely depressed–i.e., clinically

dysfunctional– patients.

In other words, antidepressants are worthless for most of the people for whom they are prescribed.

Even cautious reporters of The New York Times could no longer avoid reporting the obvious–despite efforts to deflect from the scientific verdict:

"The findings could help settle a longstanding debate about antidepressants.

While the study does not imply that the drugs are worthless for anyone with moderate to serious depression – many such people do seem to benefit – it does provide one likely explanation for the sharp disagreement among experts about the drugs’ overall effectiveness. Taken together, previous studies have painted a confusing picture. On one hand, industry-supported trials have generally found that the drugs sharply reduce symptoms. On the other, many studies that were not initially published, or were buried, showed no significant benefits compared with placebos."

Dr. Erick Turner, whose earlier study "Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy," in The New England Journal of Medicine, 2008 caused a stir among industry’s stakeholders, also avoided the inescapable conclusion, given the finding that placebos performed just as well as antidepressants without any adverse side-effects:

"I think the study could dampen enthusiasm for antidepressant medications a bit, and that may be a good thing. People’s expectations for the drugs won’t be so high, and doctors won’t be surprised if they’re not curing every patient they see with medications."

"The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be MINIMAL OR NONEXISTENT, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

No finding of a cure for ANY patient. See JAMA

The full magnitude of severe harm produced by these drugs in otherwise healthy people for whom antidepressants were misprescribed has not yet been fully collated–the human casualties include thousands of drug-induced suicides, mania, drug-exacerbated depression, drug dependence, birth defects…



Vera Hassner Sharav

THE NEW YORK TIMES

January 6, 2010

Popular Drugs May Help Only Severe Depression

By BENEDICT CAREY Some widely prescribed drugs for depression provide relief in extreme cases but are no more effective than placebo pills for most patients, according to a new analysis released Tuesday. The findings could help settle a longstanding debate about antidepressants.

While the study does not imply that the drugs are worthless for anyone with moderate to serious depression – many such people do seem to benefit – it does provide one likely explanation for the sharp disagreement among experts about the drugs’ overall effectiveness. Taken together, previous studies have painted a confusing picture. On one hand, industry-supported trials have generally found that the drugs sharply reduce symptoms. On the other, many studies that were not initially published, or were buried, showed no significant benefits compared with placebos. The new report, appearing in The Journal of the American Medical Association, reviews data from previous trials on two types of drugs and finds that their effectiveness varies according to the severity of the depression being treated. Previous analyses had found a similar pattern. But the new study is the first to analyze responses from hundreds of people being treated for more moderate symptoms, as are most people who seek care. "I think the study could dampen enthusiasm for antidepressant medications a bit, and that may be a good thing," said Dr. Erick H. Turner, a psychiatrist at Oregon Health and Science University. "People’s expectations for the drugs won’t be so high, and doctors won’t be surprised if they’re not curing every patient they see with medications." But Dr. Turner added, "The findings shouldn’t dampen expectations so much that people refuse to even try medication." A team of researchers, including psychologists who favor talk therapy and doctors who consult widely with drug makers, performed the new analysis, using government grants. The group evaluated six large drug trials, including 728 men and women, about half of them with severe depression and half with more moderate symptoms. Three of the trials were of Paxil, from GlaxoSmithKline, a so-called S.S.R.I., and the other three were of imipramine, an older generic drug from the class known as tricyclics. The team, led by Jay C. Fournier and Robert J. DeRubeis of the University of Pennsylvania, found that compared with placebos, the drugs caused a much steeper reduction in symptoms of severe depression (cases scoring 25 or higher on a standard scale of severity, putting them in the top quarter of the sample). Patients with scores of less than 25 got little or no added benefit from the medications. "We were able to give an overall estimate of effectiveness for the first time in this more moderate severity range, from 14 to 20 on the scale, in which there’s no question that doctors would likely consider prescribing medication," Dr. DeRubeis said. His co-authors included Steven D. Hollon and Dr. Richard C. Shelton of Vanderbilt University, Sona Dimidjian of the University of Colorado, Dr. Jan Fawcett of the University of New Mexico and Dr. Jay D. Amsterdam of Penn. The effects of other popular S.S.R.I.’s like Lexapro and Prozac are not likely to be much different than those of Paxil, experts said. Dr. DeRubeis and others said antidepressants’ inability to outperform placebos against moderate symptoms stemmed partly from the sustained attention that patients in drug trials received from top doctors – which itself can help relieve symptoms, drug or no drug. For some people, too, the drugs’ side effects may cancel any benefit. "The message for patients with mild to moderate depression," Dr. DeRubeis said, "is, ‘Look, medications are always an option, but there’s little evidence that they add to other efforts to shake the depression – whether it’s exercise, seeing the doctor, reading about the disorder or going for psychotherapy.’ "

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JAMA. 2010;303(1):47-53.

Antidepressant Drug Effects and Depression Severity A Patient-Level Meta-analysis Jay C. Fournier, MA; Robert J. DeRubeis, PhD; Steven D. Hollon, PhD; Sona Dimidjian, PhD; Jay D. Amsterdam, MD; Richard C. Shelton, MD; Jan Fawcett, MD

Context Antidepressant medications represent the best established treatment for major depressive disorder, but there is little evidence that they have a specific pharmacological effect relative to pill placebo for patients with less severe depression.

Objective To estimate the relative benefit of medication vs placebo across a wide range of initial symptom severity in patients diagnosed with depression.

Data Sources PubMed, PsycINFO, and the Cochrane Library databases were searched from January 1980 through March 2009, along with references from meta-analyses and reviews.

Study Selection Randomized placebo-controlled trials of antidepressants approved by the Food and Drug Administration in the treatment of major or minor depressive disorder were selected. Studies were included if their authors provided the requisite original data, they comprised adult outpatients, they included a medication vs placebo comparison for at least 6 weeks, they did not exclude patients on the basis of a placebo washout period, and they used the Hamilton Depression Rating Scale (HDRS). Data from

6 studies (718 patients) were included.

Data Extraction Individual patient-level data were obtained from study authors.

Results Medication vs placebo differences varied substantially as a function of baseline severity. Among patients with HDRS scores below 23, Cohen d effect sizes for the difference between medication and placebo were estimated to be less than 0.20 (a standard definition of a small effect).

Estimates of the magnitude of the superiority of medication over placebo increased with increases in baseline depression severity and crossed the threshold defined by the National Institute for Clinical Excellence for a clinically significant difference at a baseline HDRS score of 25.

Conclusions The magnitude of benefit of antidepressant medication compared with placebo increases with severity of depression symptoms and may be minimal or nonexistent, on average, in patients with mild or moderate symptoms. For patients with very severe depression, the benefit of medications over placebo is substantial.

Author Affiliations: Departments of Psychology (Mr Fournier and Dr DeRubeis) and Psychiatry (Dr Amsterdam), University of Pennsylvania, Philadelphia; Departments of Psychology (Dr Hollon) and Psychiatry (Dr Shelton), Vanderbilt University, Nashville, Tennessee; Department of Psychology, University of Colorado at Boulder (Dr Dimidjian); and Department of Psychiatry, University of New Mexico School of Medicine, Albuquerque (Dr Fawcett).