Eric G Smith1. 1. Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655, United States. Eric.Smith5@va.gov
Abstract
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.
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.
Authors: Hiwot Woldu; Giovanna Porta; Tina Goldstein; Dara Sakolsky; James Perel; Graham Emslie; Taryn Mayes; Greg Clarke; Neal D Ryan; Boris Birmaher; Karen Dineen Wagner; Joan Rosenbaum Asarnow; Martin B Keller; David Brent Journal: J Am Acad Child Adolesc Psychiatry Date: 2011-03-09 Impact factor: 8.829
Authors: Marcia Valenstein; Hyungjin Myra Kim; Dara Ganoczy; Daniel Eisenberg; Paul N Pfeiffer; Karen Downing; Katherine Hoggatt; Mark Ilgen; Karen L Austin; Kara Zivin; Frederic C Blow; John F McCarthy Journal: J Clin Psychopharmacol Date: 2012-06 Impact factor: 3.153