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 observed 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 the department of psychiatry at the University of Vermont, Burlington, said when asked about the added label warnings.
He added that the findings do not prove that paroxetine increases the risk of suicide during treatment but that they underscore the need for closely monitoring patients and maintaining close contact.
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. Dr. Simon also pointed out that although the findings are important, they do not offer proof of causation.
Prescribing information for paroxetine and all other antidepressants already 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.
GlaxoSmithKline stressed that findings from the current metaanalysis 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 any adverse events associated with paroxetine be reported. Reporting options include calling GlaxoSmithKline at 888-825-5249, and visiting the FDA's MedWatch adverse event reporting program online at www.fda.gov/MedWatch/report.htm