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成人急性双相躁狂的药物治疗的有效性、安全性和耐受性提供基于证据的建议。为了实现这一目标，我们使用 R 软件和相关软件包进行了系统回顾和网络元分析 (NMA)。我们检索了截至 2023 年 2 月的主要临床数据库，寻找针对成人急性双相躁狂的药物治疗和辅助治疗的随机对照试验的报告，结果包括疗效（躁狂评分从基线到终点的平均变化）、安全性（临床显着不良事件）从基线到治疗结束）和耐受性（完成整个试验达到计划终点的患者比例）。我们的分析总共纳入了 113 项研究，其中 23,491 名参与者（50.38% 为男性；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、辅助疗法中的一种治疗或安慰剂。我们的结果显示，他莫昔芬（平均差，−22.31 [−25.97，−18.63]， N = 2，n1 = 43，n2 = 39）和他莫昔芬+锂或丙戊酸钠（LIT/VAL）（−16.37 [−22.55，−10.25） ]， N = 1，n1 = 20，n2 = 20）与安慰剂相比，对患有急性双相躁狂的成人患者具有最佳和第二好的临床疗效。此外，奥氮平、帕潘立酮、喹硫平、齐拉西酮、利培酮、双丙戊酸钠和氟哌啶醇的耐受性显着优于安慰剂。抗精神病药物和 LIT/VAL 的联合治疗似乎比相应的单一疗法更有效。 虽然药物疗法与特定的常见不良事件相关，但我们没有发现与安慰剂相比头痛或抑郁事件发生率增加的证据。总体而言，我们的 NMA 为急性双相躁狂药物治疗的有效性、安全性和耐受性提供了重要见解，并可以帮助指导临床医生的治疗决策。