Paxil label to warn of suicide risk.

Paroxetine may increase the risk of suicidal behavior in adults, particularly in young adults, findings from a recent metaanalysis suggest.

"It is therefore important that all patients, especially young adults and those who are improving, receive careful monitoring during paroxetine therapy regardless of the condition being treated," the Food and Drug Administration and GlaxoSmithKline, the drug's maker and the sponsor of the study, stated in a "Dear Healthcare Provider" letter announcing a related update to the warnings section of the drug's label.

The metaanalysis, which included data from 8,958 patients with psychiatric disorders treated with paroxetine and 5,953 treated with placebo, showed that suicidal behavior occurred more often overall in adults aged 18-24 in the paroxetine (Paxil) group, compared with those in that age group in the placebo group (17 of 776, or 2.19% vs. 5 of 542, or 0.92%). The difference was not statistically significant but was seen in patients with depressive and nondepressive conditions, according to the letter.

A similar difference was not seen for adults in older age groups.

However, the metaanalysis found that among all adults in the study with major depressive disorder (MDD), suicidal behavior was significantly more common in the paroxetine group than in the placebo group (11 of 3,455, or 0.32% vs. 1 of 1,978, or 0.05%). This was despite substantial evidence showing that paroxetine was efficacious, compared with placebo for the treatment of MDD.

Of the 11 suicide attempts, none was fatal. Almost all were associated with an identified social stressor, and eight occurred in those aged 18-30 years. But because the absolute numbers are small, the FDA and GlaxoSmithKline warn that the data should be interpreted with caution. "GSK continues to believe that the overall risk: benefit of paroxetine in the treatment of adult patients with MDD and other nondepressive psychiatric disorders remains positive," the letter states.

Physicians are applauding the release of the metaanalysis results. "I'm glad to see that the data were released to the public as soon as it was available," Dr. David Fassler, of department of psychiatry at the University of Vermont, Burlington, said about the warnings.

Dr. Gregory Simon, a psychiatrist and researcher with Group Health Cooperative, Seattle, said in an interview that the new warnings are justified, despite the small number of suicide attempts in the study. On one hand, the small numbers are encouraging, suggesting that suicidal behavior is rare in these populations. On the other, they suggest that younger adult patients may indeed be at higher risk, he said.

Prescribing information for paroxetine and all other antidepressants contains warnings that patients with MDD may be at increased risk for worsening of depression or emergence of suicidal ideation and behavior, regardless of whether they are taking antidepressants, and the FDA has previously warned that paroxetine should not be used for the treatment of depression in children.

The relationship between antidepressants and suicidal behavior has remained controversial, prompting the FDA to request that drug companies examine their clinical trial data for any link between antidepressant use and suicide. The current metaanalysis was conducted in response to this request, according to GlaxoSmithKline, which also stressed that the findings do not indicate a causal relationship. The company also emphasized that the label is being amended voluntarily to emphasize the importance of careful patient monitoring.

GlaxoSmithKline asks that adverse events tied to paroxetine be reported by calling GlaxoSmithKline at 888-825-5249, and visiting the FDA's Med-Watch adverse event reporting program at www.fda.gov/MedWatch/report.htm.

BY SHARON WORCESTER

Southeast Bureau