CONTEXT:Asenapine is an approved treatment for schizophrenia in the United States. OBJECTIVE:Meta-analyses were conducted to evaluate the efficacy of asenapine in acute schizophrenia compared with placebo and other antipsychotics. DATA SOURCES:Four asenapine trials from the asenapine development program were pooled for the meta-analysis. To compare asenapine versus placebo treatment effect with other antipsychotics, we added integrated asenapine data to a previously published meta-analysis. For comparative efficacy of asenapine versus other second-generation antipsychotics (SGAs), data from a second published meta-analysis were combined with the 4 asenapine trials. DATA ANALYSES:To evaluate efficacy, mean change in Positive and Negative Syndrome Scale (PANSS) total score was examined in asenapine and other antipsychotics. To assess clinical relevance, PANSS response rates and associated odds ratios (ORs) for treatment response were assessed. To assess the relative efficacy of SGAs, a network meta-analysis with PANSS total score change was conducted by using data from the 2 published meta-analyses together with asenapine data. RESULTS:Asenapine was superior to placebo with regard to mean change in PANSS total score (last observation carried forward [LOCF]: -3.6, P = .002; mixed model for repeated measures [MMRM]: -4.1, P = .001), an effect comparable to active controls from the same trials (LOCF: -4.0, P = .002; MMRM: -4.8, P = .001). PANSS responder rates were significantly better with asenapine versus placebo (OR, 1.9; P < .001) and comparable to active controls (OR, 1.7; P = .002). Effect sizes for asenapine were somewhat lower than those reported in the literature for other SGAs. Network meta-analysis also demonstrated that the efficacy of asenapine was comparable to that of other SGAs; estimated differences between asenapine and other SGAs ranged from 3.9 points (95% CI, 0.3 to 7.4) greater than ziprasidone to 2.9 points (95% CI, -0.1 to 5.9) less than olanzapine. CONCLUSIONS:These meta-analyses indicate that the efficacy of asenapine for acute schizophrenia is superior to placebo and comparable to several other SGAs.

IntroductionWeight change and metabolic effects of atypical antipsychotics vary considerably.ObjectiveAssess weight and metabolic effects of asenapine in adults.AimDemonstrate that asenapine marketed doses are well tolerated compared with placebo or olanzapine.MethodsData were from pooled asenapine trials that used placebo (1748 patients; duration: 1−6 wk) and/or olanzapine (3430 patients; duration, 3−>100 wk) controls. Asenapine doses were 5 or 10 mg BID (2–20 mg BID in 2 studies); olanzapine doses were 5–20 mg QD. Post hoc inferential analyses based on ANOVA assessed change from baseline weight, body mass index, and fasting lipid and glucose levels.ResultsTable 1 summarizes the results.[Change From Baseline Weight and Metabolic Paramete]DiscussionThese post hoc pooled analyses support published reports and suggest asenapine was associated with moderate weight gain and increased fasting triglyceride and glucose levels vs placebo, but lower propensity for weight gain or increased serum lipids (ie, triglycerides, low-density lipoprotein, and cholesterol) vs olanzapine.

Methods The primary endpoint was change from baseline vs placebo on Young Mania Rating Scale (YMRS) total score at treatment week 3. Data for asenapine (5 or 10 mg BID) and comparators were obtained from all monotherapy (n = 20) or adjunctive treatment trials in patients showing incomplete response to lithium or valproate monotherapy (n = 10) published at the time of the analysis. Meta-analyses used a random-effects model described by DerSimonian and Laird (Control Clin Trials 1986;7:177–188). Results Treatment effects varied substantially across agents and for individual agents across trials. For monotherapy, the change from baseline in YMRS total score with asenapine exceeded placebo by 4.5 points (95% CI, 2.5–6.4; p < 0.0001); this was comparable to the treatment effect of all comparators vs placebo (4.9 points; 95% CI, 3.8–6.0). The treatment effect for adjunctive asenapine exceeded placebo by 2.4 points (95% CI, 0.5–4.3); this was also comparable to the overall treatment effect for the combined comparators (2.7 points; 95% CI, 2.0–3.3). Discussion These meta-analyses demonstrate statistical superiority of asenapine over placebo, as monotherapy or adjunctive therapy, for acute bipolar mania. Further, they reveal that the efficacy of asenapine is similar to that of other atypical antipsychotics used as monotherapy or adjunctive therapy.