Association between antidepressant half-life and the risk of suicidal ideation or behavior among children and adolescents: Confirmatory analysis and research implications

Background tudy 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. s ve risks for suicidal behavior (ideation, attempt, or preparation) for seven antidepressants were obtained from both the FDAʹs 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, Spearmanʹs rho. s ificant correlation (ρ = 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 (ρ = 0.786, p = 0.036). tions ition 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.). sions sk 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.