Suicidal adverse events in pediatric randomized, controlled clinical trials of antidepressant drugs are associated with active drug treatment: a meta-analysis.
OBJECTIVE
The aim of this study was to compare the incidence of suicidal ideation and behaviors observed with antidepressant drug treatment to the incidence with placebo, in randomized, controlled pediatric clinical trials.


METHODS
Manufacturers of nine antidepressant drugs identified suicidal adverse events in randomized, placebo-controlled, pediatric clinical trials that they had sponsored. Events were found with an electronic search for adverse event descriptions, including key words suggesting suicidal ideation or self-injury, along with a manual review of all adverse events meeting the standard regulatory definition for seriousness. Incidence rate data for these events supplied by the manufacturers were combined across trials to yield Mantel-Haenszel combined risk estimates.


RESULTS
Data from 22 randomized, short-term, placebo-controlled, pediatric trials in various indications, involving nine different antidepressant drugs, were available for analysis. A total of 2298 pediatric subjects were exposed to active drug, and 1952 to placebo. Seventy eight (78) serious suicidal adverse events occurred in these trials (54 with active drug and 24 with placebo); there were no completed suicides. The combined incidence rate ratio across all trials for serious suicidal adverse events was 1.89 (95% Confidence Interval, 1.18-3.04).


CONCLUSIONS
In short-term, placebo-controlled, pediatric studies of antidepressants, active drug treatment was associated with a rate of serious suicidal events almost twice that of placebo.
Division of Drug Risk Evaluation, Office of Drug Safety, U.S. Food and Drug Administration, Rockville, Maryland 20993, USA. andrew.mosholder@fda.hhs.gov
Andrew D
AD
Mosholder
Mary
M
Willy
D000293:Adolescent; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy / Q000453:epidemiology / Q000523:psychology; D016032:Randomized Controlled Trials as Topic; D013406:Suicide, Attempted / Q000523:psychology*
D000928:Antidepressive Agents