Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports.
Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports.
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DOI：
10.1136/bmj.i65
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发表时间：
2016-01-27
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影响因子：
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通讯作者：
Gøtzsche PC
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作者：
Sharma T;Guski LS;Freund N;Gøtzsche PC
目的 研究选择性血清素和血清素-去甲肾上腺素再摄取抑制剂的严重危害。设计系统回顾和荟萃分析。主要结果衡量死亡率和自杀率。次要结果是攻击行为和静坐不能。数据来源 从欧洲和英国药品监管机构获得的度洛西汀、氟西汀、帕罗西汀、舍曲林和文拉法辛的临床研究报告，以及来自礼来公司网站的度洛西汀和氟西汀的总结试验报告。研究选择的资格标准 双盲安慰剂对照试验，包含任何患者叙述或个别患者列出的危害。数据提取与分析 两名研究人员独立提取数据；结果通过 Peto 精确方法（固定效应模型）进行荟萃分析。结果 我们纳入了 70 项试验（64 381 页临床研究报告），涉及 18 526 名患者。这些试验在研究设计方面存在局限性，并且报告存在差异，这可能导致严重少报危害。例如，一些结果仅出现在附录中的个别患者列表中，而我们只有 32 项试验的列表，而且我们没有任何试验的病例报告表。死亡率（所有死亡均发生在成人中，比值比为 1.28，95% 置信区间为 0.40 至 4.06）、自杀倾向（1.21、0.84 至 1.74）和静坐不能（2.04、0.93 至 4.48）的差异并不显着，而服用抗抑郁药的患者则表现出更具攻击性的行为（1.93、1.26 至 1.74）。 2.95）。对于成年人来说，自杀的比值比为 0.81（0.51 至 1.28），攻击性的比值比为 1.09（0.55 至 2.14），静坐不能的比值比为 2.00（0.79 至 5.04）。儿童和青少年的相应值为2.39（1.31至4.33）、2.79（1.62至4.81）和2.15（0.48至9.65）。在礼来公司网站上的总结试验报告中，几乎记录了所有死亡，但缺少所有自杀意念事件，并且有关其余结果的信息不完整。结论 由于所发现的缺陷，且只能查阅部分附录，无法查阅病例报告表，因此无法准确估计危害。在成人中，所有四种结果均没有显着增加，但在儿童和青少年中，自杀和攻击性的风险增加了一倍。为了可靠地阐明危害，需要访问匿名的个体患者数据。
Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors. Design Systematic review and meta-analysis. Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia. Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms. Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model). Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete. Conclusions Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.