Objective:

Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression treated or not treated with antidepressants over a 1-year period.

Methods:

The authors emulated a target trial using observational data from nationwide Danish health registers. The study included 979 individuals with bipolar depression recently discharged from a psychiatric ward. Of these, 358 individuals received antidepressant treatment, and 621 did not. The occurrence of mania and bipolar depression over the following year was ascertained, and the intention-to-treat effect of antidepressants was analyzed by using Cox proportional hazards regression with adjustment for baseline covariates to emulate randomized open-label treatment allocation.

Results:

The fully adjusted analyses revealed no statistically significant associations between treatment with an antidepressant and the risk of mania in the full sample (hazard rate ratio=1.08, 95% CI=0.72–1.61), in the subsample concomitantly treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.63–2.13), and in the subsample not treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.65–2.07). Secondary analyses revealed no statistically significant association between treatment with an antidepressant and bipolar depression recurrence.

Conclusions:

These findings suggest that the risk of antidepressant-induced mania is negligible and call for further studies to optimize treatment strategies for individuals with bipolar depression.

中文翻译：

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一项全国性目标试验模拟，评估双相抑郁症患者抗抑郁药诱发的躁狂风险

 目的：

抗抑郁药通常用于治疗双相抑郁症，但可能会增加躁狂症的风险。然而，来自随机对照试验的证据受到治疗持续时间短的限制，几乎没有提供抗抑郁药诱发的躁狂症的长期风险证据。作者进行了一项目标试验模拟，以比较 1 年期间接受或未接受抗抑郁药治疗的双相抑郁症患者患躁狂症的风险。

 方法：

作者使用来自丹麦全国健康登记处的观察数据模拟了一项目标试验。该研究包括 979 名最近从精神病房出院的双相抑郁症患者。其中，358 人接受了抗抑郁治疗，621 人没有。确定了接下来一年躁狂症和双相抑郁症的发生，并通过使用 Cox 比例风险回归分析抗抑郁药的意向性治疗效果，并调整基线协变量以模拟随机开放标签治疗分配。

 结果：

完全调整的分析显示，在全样本中（风险率比=1.08,95% CI=0.72-1.61）、同时接受情绪稳定剂治疗的子样本（风险率比=1.16,95% CI=0.63-2.13）和未接受情绪稳定剂治疗的子样本（风险率比=1.16， 95% CI = 0.65–2.07）。二次分析显示，抗抑郁药治疗与双相抑郁复发之间没有统计学意义的关联。

 结论：

这些发现表明，抗抑郁药诱发的躁狂症的风险可以忽略不计，需要进一步研究以优化双相抑郁症患者的治疗策略。