Bicyclic Antidepressants - Publication Bias

Publication Bias

A review of antidepressant trials submitted to the U.S. Food and Drug Administration (FDA) by the industry for drug approval revealed that when a trial was successful, the results of the trial was published 94% of the time, however, when the trial was not found to be more effective than placebo, it was only published 50% of the time. This demonstrated a measure of bias in reporting by industry. Combined, 51% of all studies showed efficacy. The difference in effect between active placebos and several anti-depressants appeared small and strongly affected by publication bias. Combined, 51% of all studies showed efficacy. The difference in effect between active placebos and several anti-depressants appeared small and strongly affected by publication bias. Several studies have stimulated doubt about the effectiveness of antidepressants. A 2002 study cited that the difference between antidepressants and placebo is close to negligible.

(2002) Article in The Washington Post titled "Against Depression, a Sugar Pill Is Hard to Beat" stated, "A new analysis has found that in the majority of trials conducted by drug companies in recent decades, sugar pills have done as well as—or better than—antidepressants. Companies have had to conduct numerous trials to get two that show a positive result, which is the Food and Drug Administration's minimum for approval. What's more, the sugar pills, or placebos, cause profound changes in the same areas of the brain affected by the medicines, according to research published last week... the makers of Prozac had to run five trials to obtain two that were positive, and the makers of Paxil and Zoloft had to run even more... When Leuchter compared the brain changes in patients on placebos, he was amazed to find that many of them had changes in the same parts of the brain that are thought to control important facets of mood... Once the trial was over and the patients who had been given placebos were told as much, they quickly deteriorated. People's belief in the power of antidepressants may explain why they do well on placebos..."

Through a Freedom of Information Act request, two psychologists obtained 47 studies used by the FDA for approval of the six antidepressants prescribed most widely between 1987-99. Overall, antidepressant pills worked 18% better than placebos, a statistically significant difference, "but not meaningful for people in clinical settings", says psychologist Irving Kirsch, lead author of the study. He and co-author Thomas Moore released their findings in "Prevention and Treatment", an e-journal of the American Psychological Association. In a later publication, Kirsch concluded that the overall effect of new-generation antidepressant medication is below recommended criteria for clinical significance.

Another study by psychologists at the University of Pennsylvania, Vanderbilt University, the University of Colorado, and the University of New Mexico also found that antidepressant drugs hardly have better effects than a placebo in those cases of mild or moderate depression. The study was published in the Journal of the American Medical Association. The study focused on paroxetine (Paxil) from GlaxoSmithKline and imipramine.

In 2005, anti-depressants became the most prescribed drug in the United States, causing more debate over the issue. Some doctors believe this is a positive sign that people are finally seeking help for their issues. Others disagree, saying that this shows that people are becoming too dependent on anti-depressants.

Other notable psychiatrists and authors remain skeptical not only about the efficacy of anti-depressants or their overuse but also about the very principle of prescribing a mind-altering medications to treat something that cannot be objectively proven to be a biological disorder resulting from a chemical imbalance, yet is often presumed to be so. Professor of Psychiatry Thomas Szasz argues mental illness is a social phenomenon rather than a biological disease entity. Harvard-trained psychiatrist Peter Breggin argues that " 'work' by causing mental disabilities such as apathy and euphoria that are misinterpreted as improvements" Cambridge-educated Bob Johnson, GP, Psychiatrist and author, argues that all psychiatric medications are emotionally damaging both due to the physical effects of the drugs and because they detract from addressing the root cause of depression, which is to be found, he argues, in the form of unaddressed fears - a product of mind and consciousness, rather than a biological imbalance; and a problem that he argues is more effectively treated by psychological or social interventions than by drug treatment. Meanwhile Joanna Moncrieff, an academic psychiatrist, argues more pragmatically against the effectiveness of anti-depressants in her book 'The Myth of the Chemical Cure.' In his book, 'The Emperor's New Drugs,' psychologist Irving Kirsch argues that the small benefit of antidepressants over placebo might itself be an "enhanced" placebo effect, brought about because patients in clinical trials are able to figure out whether they have been given the drug or the placebo on the basis of side-effects. Robert Whitaker, an award-winning journalist, argues in his books, including 'Mad in America,' and 'Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America,' which have been highly critical of the profession of psychiatry, that large quantities of evidence about the harm caused by psychotropic drugs including anti-depressants is overlooked and evidence regarding antidepressant efficacy is overstated. These voices critical of the use of anti-depressants are in a minority among psychiatric professionals who generally advocate use of medications according to the evidence base evolved from numerous large drug trials. Some critics, however, argue these drugs trials are subject to bias. There is strong opposition to forced or coerced treatment, poor disclosure of side effects, or lack of informed consent, from consumer advocacy groups, grass roots movements, psychiatric survivors, and antidepressant withdrawal support groups.