Association between antidepressant half-life and the risk of suicidal ideation or behavior among children and adolescents: confirmatory analysis and research implications
Department of Psychiatry
Medical Subject Headings
Adolescent; Antidepressive Agents; effects; Child; Clinical Trials as Topic; Depressive Disorder; Dose-Response Relationship, Drug; Half-Life; Humans; Risk Assessment; Risk Factors; Serotonin Uptake Inhibitors; effects; *Suicide; *Suicide, Attempted; United States; United States Food and Drug Administration
BACKGROUND: This study sought to determine from a recent meta-analysis of pediatric antidepressant trials if a general property of antidepressant medications--the multiple-dosing medication half-life--is associated with risks for suicidal ideation or behavior.
METHODS: Relative risks for suicidal behavior (ideation, attempt, or preparation) for seven antidepressants were obtained from both the FDA's initial and published versions of their pediatric antidepressant meta-analysis. The correlation between the relative risk for suicidal behavior and antidepressant half-life was examined using a nonparametric test, Spearman's rho.
RESULTS: A significant correlation (rho=0.929; p=0.003) was observed for the initial analysis, as previously reported by Weiss and Gorman. The correlation was robust to a change in the suicidality ranking for the longest half-life medication, fluoxetine, that occurred when results from the Treatment of Adolescent Depression Study (TADS) were included in the published meta-analysis (rho=0.786, p=0.036).
LIMITATIONS: In addition to limitations common to meta-analyses, our analysis has additional uncertainties including the fact that adult, rather than pediatric, antidepressant half-life data were used due to an unavailability of published information. In addition, risks for suicidal ideation/behavior may vary for reasons other than half-life (e.g. study eligibility criteria, illness severity or responsiveness to treatment, diagnoses, etc.).
CONCLUSIONS: The risk of suicidal ideation or behavior in short-term antidepressant trials involving children or adolescents, as defined in the recent FDA meta-analysis, appears to be potentially at least partly associated with antidepressant half-life. Although any relationship is tentative, approaches to investigating several potential candidate mechanisms for any association are discussed.
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Citation: J Affect Disord. 2009 Apr;114(1-3):143-8. Epub 2008 Aug 8. Link to article on publisher's site