Switch to mania after acute antidepressant treatment for bipolar depression: a systematic review and network meta-analysis of randomised controlled trials.
Vincenzo Oliva, Michele De Prisco, Enrico La Spina, Sofia Paolucci, Giovanna Fico, Gerard Anmella, Diego Hidalgo-Mazzei, Andrea Murru, Maurizio Pompili, Michele Fornaro, Marco Solmi, Ayşegül Yildiz, Stefan Leucht, Eduard Vieta, Joaquim Radua
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引用次数: 0
Abstract
Background: The potential for antidepressants to induce a switch to mania remains a major concern in the treatment of bipolar depression, but the specific risk associated with different antidepressants remains unclear. This systematic review and network meta-analysis (NMA) assessed this risk by comparing individual antidepressants with each other and with a common placebo.
Methods: In this systematic review and network meta-analysis, we searched ClinicalTrials.gov, CENTRAL, PsycINFO, PubMed, Scopus, and Web of Science from database inception up to Feb 19, 2025, with no language restrictions, for randomised controlled trials (RCTs) assessing acute antidepressant treatment in bipolar depression. The primary outcome was the rate of switch to mania after antidepressant treatment. A frequentist NMA estimated risk ratios (RRs) and 95% confidence intervals. Sensitivity analyses were performed based on treatment regimen (monotherapy or add-on), baseline severity, switch to mania definition, study setting, psychiatric comorbidity, treatment duration, non-pharmacological combinations, industry sponsorship, and risk of bias. Certainty of evidence was assessed using the CINeMA framework. The protocol was preregistered on the Open Science Framework.
Findings: Of 2434 records screened, 13 RCTs (1362 patients; 818 [60.1%] female, 511 [37.5%] male, and 33 [2.4%] not disclosed) were included in the NMA. Although some evidence of increased risk of switching to mania was observed, no antidepressant was associated with a significantly higher risk of switch to mania compared to placebo. Venlafaxine showed the highest risk estimate among antidepressants, though not statistically significant RR (4.53 [95% CI 0.47-43.25]), and was the only compound with consistent signals of increased switch in individual studies. The evidence base was larger for add-on therapy, while fewer data were available for monotherapy. Sensitivity analyses confirmed the results. Heterogeneity was low. Overall confidence in the evidence was rated as low.
Interpretation: Antidepressants remain a treatment option for acute bipolar depression, particularly as add-on therapy. Their use should be individualised, considering patient-specific profiles and other potential risks, in line with a precision psychiatry approach. Further studies are needed to clarify long-term safety.
背景：抗抑郁药诱导躁狂症转变的可能性仍然是双相抑郁症治疗中的一个主要问题，但与不同抗抑郁药相关的具体风险尚不清楚。本系统综述和网络荟萃分析（NMA）通过比较单个抗抑郁药和普通安慰剂来评估这种风险。方法：在这项系统综述和网络荟萃分析中，我们检索了ClinicalTrials.gov、CENTRAL、PsycINFO、PubMed、Scopus和Web of Science，从数据库建立到2025年2月19日，无语言限制，以评估双相抑郁症急性抗抑郁治疗的随机对照试验（RCTs）。主要结果是抗抑郁治疗后转为躁狂的比率。频率学家NMA估计风险比（rr）和95%置信区间。敏感性分析基于治疗方案（单一治疗或附加治疗）、基线严重程度、转向躁狂症定义、研究环境、精神合并症、治疗持续时间、非药物联合、行业赞助和偏倚风险。使用CINeMA框架评估证据的确定性。该方案在开放科学框架上进行了预注册。结果：在筛选的2434份记录中，13项rct（1362例患者，818例[60.1%]女性，511例[37.5%]男性，33例[2.4%]未披露）被纳入NMA。虽然观察到一些证据表明转向躁狂症的风险增加，但与安慰剂相比，抗抑郁药与转向躁狂症的风险没有显著增加相关。文拉法辛在抗抑郁药中显示出最高的风险估计，尽管没有统计学上显著的RR (4.53 [95% CI 0.47-43.25])，并且是唯一在个体研究中具有一致信号的化合物。附加治疗的证据基础更大，而单一治疗的数据较少。敏感性分析证实了这一结果。异质性低。对证据的总体信心被评为低。解释：抗抑郁药仍然是急性双相抑郁症的一种治疗选择，特别是作为附加治疗。它们的使用应该是个体化的，考虑到患者的具体情况和其他潜在风险，符合精确精神病学的方法。需要进一步的研究来阐明其长期安全性。资金:没有。
期刊介绍：
eClinicalMedicine is a gold open-access clinical journal designed to support frontline health professionals in addressing the complex and rapid health transitions affecting societies globally. The journal aims to assist practitioners in overcoming healthcare challenges across diverse communities, spanning diagnosis, treatment, prevention, and health promotion. Integrating disciplines from various specialties and life stages, it seeks to enhance health systems as fundamental institutions within societies. With a forward-thinking approach, eClinicalMedicine aims to redefine the future of healthcare.
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