Smith Eric G
Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Avenue, Worcester, MA 01655, United States.
J Affect Disord. 2009 Apr;114(1-3):143-8. doi: 10.1016/j.jad.2008.06.018. Epub 2008 Aug 8.
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.
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.
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).
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.).
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.
本研究旨在通过近期对儿科抗抑郁药物试验的荟萃分析，确定抗抑郁药物的一个普遍特性——多次给药后的药物半衰期——是否与自杀意念或行为风险相关。
从美国食品药品监督管理局（FDA）儿科抗抑郁药物荟萃分析的初始版本和已发表版本中获取七种抗抑郁药物的自杀行为（意念、企图或准备）相对风险。使用非参数检验斯皮尔曼等级相关系数（Spearman's rho）来检验自杀行为相对风险与抗抑郁药物半衰期之间的相关性。
正如韦斯（Weiss）和戈尔曼（Gorman）之前所报道的，初始分析观察到显著相关性（rho = 0.929；p = 0.003）。当将青少年抑郁症治疗研究（TADS）的结果纳入已发表的荟萃分析时，半衰期最长的药物氟西汀的自杀性排名发生了变化，但该相关性依然显著（rho = 0.786，p = 0.036）。
除了荟萃分析常见的局限性外，我们的分析还有其他不确定性，包括由于未找到已发表的信息而使用了成人而非儿科抗抑郁药物半衰期数据这一事实。此外，自杀意念/行为风险可能因半衰期以外的其他原因而有所不同（例如研究纳入标准、疾病严重程度或对治疗的反应、诊断等）。
近期FDA荟萃分析所定义的涉及儿童或青少年的短期抗抑郁药物试验中，自杀意念或行为风险似乎可能至少部分与抗抑郁药物半衰期相关。尽管这种关系是初步的，但本文讨论了研究任何关联的几种潜在候选机制的方法。
