FDA proposal on antidepressants is premature and may be counterproductive

Sep 23 2004

The recent FDA proposal to force antidepressants to carry warnings about increased suicide risk is the subject of a pair of articles by leading experts in The Annals of Pharmacotherapy.

According to "Antidepressants, Suicide, and the FDA: A Loose Association," the FDA proposal is premature and may be counterproductive. The companion piece "Antidepressants: an Avoidable and Solvable Controversy" cautions the warnings simply don't address the fundamental problem. Both articles are posted at The Annals of Pharmacotherapy's Articles Ahead of Print and will appear in the journal's October issue.

In "Antidepressants, Suicide, and the FDA: A Loose Association," author Patrick R Finley PharmD, Professor of Clinical Pharmacy, Psychopharmacology and Behavioral Health at the University of California at San Francisco, notes that although the FDA warning appears reasonable, it has generated considerable controversy. Perhaps most notably, the warning may discourage depressed patients from seeking appropriate medical care.

Based on thousands of patients evaluated over the years, many experts see no conclusive evidence that selective serotonin reuptake inhibitors (SSRIs), the antidepressants in question, increase suicide risk in adults. Instead, trends have actually shown a decrease in numbers of suicides over the years that SSRI use has grown. However, caution should be used when interpreting these data, Finley notes. In particular, antidepressant studies in children and adolescents are much more limited, with more studies needed even to show conclusively that SSRIs work in kids.

Ultimately, improvements in clinical trial designs for SSRIs and other psychotropic medications may clarify any suicide risk. Possible strategies include better tests to identify suicidal tendencies, more variety in patient selection, and improved postmarketing surveillance. Until then, it's important to remind patients that untreated depression carries a much higher suicide risk than any antidepressant medication.

The article series continues with "Antidepressants: an Avoidable and Solvable Controversy," by Jay S. Cohen, M.D., Associate Professor (voluntary) of Family and Preventive Medicine and of Psychiatry at the University of California, San Diego. Dr. Cohen highlights how poor FDA and drug industry procedures often lead to the approval and prescribing of drug doses that are too strong for many patients. As a result, many suffer unnecessarily from dose-related side effects.

In the case of antidepressants, mild depression is often treated with doses studied for major depression. Typically, study results are averaged and information on the wide range of individual patient responses is ignored, according to Cohen. Also, studies often lack elderly subjects, obese or underweight patients, and those taking other medications that might interfere with antidepressants. In addition, usually no accommodation is made for patients with long histories of medication reactions or sensitivities. Cohen states, "All of these factors lead to a lack of precision in how antidepressants are prescribed to individuals." The article cites others who have mirrored these findings as well.

Cohen calls on both the drug industry and FDA to provide better dose-response research. This includes full disclosure about all doses found superior to placebo in clinical trials. Additionally, he asks for better guidelines on treating the various depressive disorders and individualizing treatment based on individual patient needs and tolerances.

Ultimately, new warnings may improve awareness about risks, but more is needed to reinforce patient trust while improving prescriber skill and confidence. To ensure the greatest level of patient safety and maximize treatment effectiveness, practical dosing strategies that minimize risks with antidepressants are required.