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


CONCLUSIONS
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.
Smith
Eric G
EG
Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655, United States. Eric.Smith5@va.gov
D000293:Adolescent; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D002648:Child; D002986:Clinical Trials as Topic; D003866:Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D006801:Humans; D018570:Risk Assessment; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013405:Suicide / Q000523:psychology; D013406:Suicide, Attempted / Q000523:psychology; D014481:United States; D014486:United States Food and Drug Administration
D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors