![]() The primary outcomes for efficacy and acceptability were response to treatment and all-cause discontinuation, respectively. ![]() Data synthesis, outcome measures, and data extraction We searched PubMed, the Cochrane Library, and Embase databases for studies published before March 14, 2021. The exclusion criteria were as follows: (1) open-label studies, (2) studies in which selection bias was evaluated as high risk according to the Cochrane risk of bias (ROB) criteria, (3) studies including children/adolescents with mania, (4) studies that included individuals with a dual diagnosis of BD and other disorders, (5) studies that allowed antipsychotics as a rescue medication during a trial, and (6) studies that terminated early without efficacy analysis. The inclusion criteria for studies were as follows: (1) published and unpublished randomized controlled trials (RCTs) of oral monotherapy lasting for ≥10 days, (2) studies of adults with acute bipolar mania, and (3) double- and single-blind studies. Search strategy and inclusion criteriaĭetailed information about the search strategy is shown in Supplementary Fig. At least two authors double-checked the literature search, data transfer accuracy, and calculations. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Supplementary Table S1) and was registered on the Open Science Framework ( ). Therefore, we conducted a systematic review and network meta-analysis for 21 outcomes related to the efficacy, acceptability, tolerability, and safety of 23 drugs in the treatment of adults with acute bipolar mania. Moreover, these network meta-analyses did not evaluate the following important outcomes: clinical remission, efficacy for psychotic symptoms, and the risk of individual adverse events. However, clinical trials of some newer drugs have been conducted for individuals with acute mania after publication of these meta-analyses. ![]() The acute mania section in these guidelines was developed evidence-based recommendations citing two important network meta-analyses. Recent guidelines recommend various second generation antipsychotics (SGAs), lithium, and valproate as first-line monotherapy for adults with acute mania. Pharmacotherapy is one of the main treatments for acute bipolar mania. Acute bipolar mania can be a medical emergency, often leading to psychiatric hospitalization to protect individuals from hyperactive and impulsive activity, and sometimes involving the intervention of law enforcement agencies responding to dangerous behavior. Similar content being viewed by othersīipolar disorder (BD) is a severe chronic mood disorder characterized by episodes of mania, hypomania, and alternating or intertwining episodes of depression, with a worldwide prevalence of ~1%. However, only aripiprazole, olanzapine, quetiapine, and risperidone had better acceptability than the placebo. In conclusions, these antipsychotics, carbamazepine, lithium, tamoxifen, and valproate were effective for acute mania. Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed the improvement of mania symptoms ( N = 61, n = 15466), and aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, valproate, and ziprasidone had lower discontinuation due to inefficacy ( N = 50, n = 14284). Compared with the placebo, aripiprazole, asenapine, carbamazepine, cariprazine, haloperidol, lithium, olanzapine, paliperidone, quetiapine, risperidone, tamoxifen, valproate, and ziprasidone outperformed response to treatment ( N = 56, n = 14503) aripiprazole, olanzapine, quetiapine, and risperidone had lower all-cause discontinuation however, topiramate had higher all-cause discontinuation ( N = 70, n = 16324). Of the 79 eligible RCTs, 72 double-blind RCTs of 23 drugs and a placebo were included in the meta-analysis (mean study duration = 3.96 ± 2.39 weeks, n = 16442, mean age = 39.55 years, with 50.93% males). The secondary outcomes were the improvement of mania symptoms and discontinuation due to inefficacy. The primary outcomes were response to treatment (efficacy) and all-cause discontinuation (acceptability). Randomized controlled trials (RCTs) of oral medication monotherapy lasting ≥10 days in adults with mania were included, and studies that allowed the use of antipsychotics as a rescue medication during a trial were excluded. We searched PubMed, the Cochrane Library, and Embase databases for eligible studies published before March 14, 2021. A systematic review and random-effects model network meta-analysis was conducted to compare the efficacy, acceptability, tolerability, and safety of pharmacological interventions for adults with acute bipolar mania.
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