Efficacy and safety of asenapine in Asian patients with an acute exacerbation of schizophrenia: a multicentre, randomized, double-blind, 6-week, placebo-controlled study

Abstract

RationaleAsenapine is a second generation anti-psychotic approved in the USA in 2009 for the treatment of schizophrenia, but its efficacy has not been proven in Asian patients.ObjectivesThe objectives of this study are to evaluate the efficacy and tolerability of asenapine in Asian patients experiencing an acute exacerbation of schizophrenia.MethodsIn this prospective, double-blind study, patients in Japan, Korea, and Taiwan were randomized (1:1:1) to asenapine 5 mg twice daily (bid), 10 mg bid or placebo for 6 weeks after a 3- to 7-day washout/screening period. The primary endpoint was the mean change in the positive and negative syndrome scale (PANSS) total score from baseline to day 42/treatment end.ResultsOf the 532 participants randomized, 530 received treatment. The primary endpoint was significantly greater with asenapine 5 and 10 mg bid than with placebo (−12.24 and −14.17 vs. −0.95; p < 0.0001). The results of secondary endpoints including PANSS negative subscale scores and PANSS responders at the end of treatment supported the results of the primary endpoint. There were no significant differences in the incidence of treatment-emergent adverse events reported with asenapine 5 and 10 mg bid and placebo (84.6, 80.7, and 81.6 %). There was a mean (± standard deviation) change in weight of −1.76 ± 2.45 kg for placebo, +0.42 ± 2.65 kg for asenapine 5 mg bid, and +0.81 ± 2.89 kg for asenapine 10 mg bid group.ConclusionsAsenapine was effective and generally well tolerated when used for the treatment of acute exacerbations of schizophrenia in Asian patients.

<p>Transdermal Asenapine in Schizophrenia: A Systematic Review</p>

“…53 This is comparable to changes seen with sublingual asenapine in schizophrenia. 26 , 27 This translates in a number needed to treat (NNT) of 9 for low-dose transdermal asenapine and 10 for high-dose transdermal asenapine. 53 This is comparable to an NNT for acute psychosis in schizophrenia with sublingual asenapine (administered at 5 mg BID).…”

“…Asenapine is a novel second-generation antipsychotic with a unique receptor profile (Table 2) that has been approved in its sublingual formulation for treatment of people with schizophrenia and bipolar disorder. [24][25][26][27] Its exact mechanism of action in schizophrenia and bipolar disorder is unknown, but it has a unique human receptor signature, with binding affinity and receptor profiles that differ considerably from other antipsychotic drugs. It has antagonist activity for the D 3 , D 4 , 5HT 2A , 5HT 2C , 5HT 2B , 5HT 7 , and 5HT 6 , histamine type 1 (H 1 ), and alpha adrenergic type 2 (α2)-receptors, all at higher affinity than to the dopamine type 2 (D 2 ) receptor (Table 2).…”

Blonanserin patch vs. Other Antipsychotics for Acute Schizophrenia: A Systematic Review of Double-blind, Randomized, Placebo-controlled, Phase 3 Trials in Japan

“…Other outcomes were the PANSS subscale scores, response rates (defining a response as a reduction in the total PANSS score of at least 30 %), all-cause discontinuation, and the incidence of individual adverse events. A characteristic adverse event associated with ASE was oral hypoesthesia [17]; however, this outcome was not reported for the other antipsychotics, so we have presented the statistical results for ASE only. The PAL-ER trial did not include a determination of metabolic parameters and blood prolactin concentrations, so our analysis of these parameters was based on data from the other 3 trials.…”

“…Various antipsychotics have been approved for schizophrenia treatment in Japan; however, the only antipsychotic medications for which there have been 6-week, double-blind, randomized, placebo-controlled trials as phase 3 trials in Japan are asenapine (ASE) [17], BLO-P [14], brexpiprazole (BRE) [18], and paliperidone extended-release (PAL-ER) [19]. All of these were included in the review.…”

“…The ASE and BLO-P trials included 2 dose arms: ASE, 10 mg/ day (ASE10) and 20 mg/day (ASE20); and BLO-P, 40 mg/day (BLO-P40) and 80 mg/day (BLO-P80). However, these trials did not include direct comparisons of efficacy and safety outcomes between the dose arms [14,17], so we also investigated whether there were differences between the dose arms in those studies (ASE10 vs. ASE20 and BLO-P40 vs. BLO-P80).…”