Huang Wenbo, He Shuyang, Liu Mingxin, Xu Jilai
Department of Medicine, Beijing Municipal Welfare Medical Research Institute Ltd, Beijing, China.
Applied Oral Sciences & Community Dental Care, Faculty of Dentistry, The University of Hong Kong, Hong Kong, China.
Mol Psychiatry. 2025 Mar;30(3):838-847. doi: 10.1038/s41380-024-02705-3. Epub 2024 Aug 27.
The aim of this study was to provide evidence-based recommendations regarding the efficacy, safety, and tolerability of currently used pharmacological treatments for adults with acute bipolar mania. To achieve this, we conducted a systematic review and network meta-analysis (NMA) using R software and related packages. We searched primary clinical databases until February 2023 for reports of randomized controlled trials of drug treatments and adjunctive therapies for adults with acute bipolar mania, with outcomes including efficacy (mean change from baseline to endpoint in mania rating scores), safety (clinically significant adverse events from baseline to end of treatment), and tolerability (the proportion of patients who completed the whole trial to the planned endpoint). A total of 113 studies were included in our analysis, in which 23,491 participants (50.38% males; mean age = 38.6 years; mean study duration = 3.39 weeks; mean manic baseline score = 29.37) were randomly allocated to one of 51 monotherapies, adjunctive treatments, or placebo. Our results showed that tamoxifen (mean difference, -22.31 [-25.97, -18.63], N = 2, n1 = 43, n2 = 39) and tamoxifen+ lithium or valproate (LIT/VAL) (-16.37 [-22.55, -10.25], N = 1, n1 = 20, n2 = 20) had the best and second-best clinical efficacy in adults with acute bipolar mania over the placebo. Furthermore, olanzapine, paliperidone, quetiapine, ziprasidone, risperidone, divalproex, and haloperidol were significantly better tolerated than placebo. Combination therapies of antipsychotics and LIT/VAL appeared to be more effective than their corresponding monotherapies. While pharmacotherapies were associated with specific common adverse events, we found no evidence of increased incidence of headache or depression events compared to the placebo. Overall, our NMAs provided important insights into the effectiveness, safety, and tolerability of pharmacological treatments for acute bipolar mania and can help guide treatment decisions for clinicians.
本研究的目的是就目前用于治疗成人急性双相躁狂症的药物治疗的疗效、安全性和耐受性提供循证建议。为实现这一目标，我们使用R软件及相关程序包进行了一项系统评价和网状Meta分析（NMA）。我们检索了主要临床数据库，直至2023年2月，以获取关于成人急性双相躁狂症药物治疗和辅助治疗的随机对照试验报告，结局包括疗效（躁狂评分从基线到终点的平均变化）、安全性（从基线到治疗结束的具有临床意义的不良事件）和耐受性（完成整个试验至计划终点的患者比例）。我们的分析共纳入113项研究，其中23491名参与者（男性占50.38%；平均年龄 = 38.6岁；平均研究持续时间 = 3.39周；平均躁狂基线评分 = 29.37）被随机分配至51种单一疗法、辅助治疗或安慰剂中的一种。我们的结果显示，他莫昔芬（平均差值，-22.31 [-25.97, -18.63]，N = 2，n1 = 43，n2 = 39）以及他莫昔芬 + 锂盐或丙戊酸盐（LIT/VAL）（-16.37 [-22.55, -10.25]，N = 1，n1 = 20，n2 = 20）在成人急性双相躁狂症患者中，相较于安慰剂具有最佳和次佳的临床疗效。此外，奥氮平、帕利哌酮、喹硫平、齐拉西酮、利培酮、丙戊酸和氟哌啶醇的耐受性显著优于安慰剂。抗精神病药物与LIT/VAL的联合疗法似乎比相应的单一疗法更有效。虽然药物治疗与特定的常见不良事件相关，但我们未发现相较于安慰剂，头痛或抑郁事件发生率增加的证据。总体而言，我们的NMA为急性双相躁狂症药物治疗的有效性、安全性和耐受性提供了重要见解，并有助于指导临床医生的治疗决策。
