For decades, some physicians have suspected that patients' risk of suicidality (suicidal thoughts and behavior) increased when pediatric patients first began taking antidepressants, according to background information in the article. Research indicates that there is no such association in adults. In 2003, a report submitted to the Food and Drug Administration (FDA) suggested a link between the antidepressant paroxetine and suicidality in pediatric patients. The FDA then requested pediatric data from the manufacturers of eight other antidepressant drugs, the authors report.
Tarek A. Hammad, M.D., Ph.D., and colleagues at the FDA performed a meta-analysis of data from 23 short-term clinical trials received in response to the request, as well as one trial funded by the National Institute of Mental Health (NIMH). The 24 studies included 4,582 pediatric patients taking one of nine antidepressant medications for depression, anxiety or other psychiatric disorder.
No children committed suicide in any of the trials. Although the NIMH-funded trial was the only individual trial to show a significant increase in suicidality among children taking antidepressants, the analysis of all the trials together showed a higher risk of suicidal ideation and behavior for children taking the drugs compared with those who were not. "When considering 100 treated patients, we might expect one to three patients to have an increase in suicidality beyond the risk that occurs with depression itself owing to short-term treatment with an antidepressant," the authors write.
The FDA now requires warnings regarding the risk of suicidality in children on antidepressant labeling and the distribution of a patient medication guide to patients, families and caregivers, the authors write. "Although there remain differences of opinion in the clinical community about the strength of this signal for antidepressant drug–induced suicidality in pediatric patients and the implications for clinical practice, it is important to be clear that the FDA has not contraindicated any of the antidepressant drugs for pediatric use," they conclude. "The FDA recognizes that depression and other psychiatric disorders in pediatric patients can have significant consequences if not appropriately treated. The new warning language recognizes this need but advises close monitoring of patients as a way of managing the risk of suicidality."
(Arch Gen Psychiatry. 2006;63:332-339. Available pre-embargo to the media at www.jamamedia.org.)
Editorial: Suicidal Behavior Different from Suicide Attempts The small number of suicide attempts across the trials make the results of the meta-analysis difficult for physicians and policymakers to use, write Ross J. Baldessarini, M.D., of McLean Hospital, Belmont, Mass., and colleagues in an accompanying editorial.
Measuring suicidality rather than suicides or suicide attempts may not paint an accurate picture of the risk associated with the drugs, they continue. "Only a small fraction of patients with suicidal thoughts attempt suicide, few attempts prove to be fatal and risk factors for suicide attempts (e.g., younger, female) and completions (e.g., older, male) differ markedly," they write. "Moreover, suicidal ideation, but usually not suicidal behavior, has been reduced with antidepressant drug treatment."
"When adverse responses do occur, they are often detectable with close clinical follow-up and psychological support, especially early in treatment, as recommended in recent FDA clinical advisories," they conclude. "Moreover, they may be reversed with appropriately modified treatment."
(Arch Gen Psychiatry. 2006;63:127-128. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: This commentary was supported, in part, by a grant from the Bruce J. Anderson Foundation, Boston, and the McLean Private Donors Bipolar Disorders and Psychopharmacology Research Fund, Boston (Dr. Baldessarini), by a University of Rome fellowship and by National Alliance for Research on Schizophrenia and Depression, Great Neck, N.Y. Full financial disclosures are available in the article.
To contact corresponding editorialist Ross J. Baldessarini, M.D., call Cynthia Lepore at 617-855-2110.
Journal
Archives of General Psychiatry