Comparative efficacy and safety of antipsychotics in the treatment of schizophrenia: a network meta-analysis in a Japanese population

Abstract

BackgroundThe relative efficacy and tolerability of antipsychotics for schizophrenia are considerably well studied. This study aimed to examine whether previous findings could be replicated in a genetically distinct and homogenous group (ie, Japanese patients with schizophrenia) and whether previous findings could be extended to a broader range of antipsychotics with previously unclear relative efficacy and tolerability.MethodsBayesian network meta-analysis was performed in which randomized trials comparing any of the following interventions were included: second-generation antipsychotics, haloperidol, or placebo. The primary outcomes for efficacy and acceptability were the response rate and all-cause discontinuation. The secondary outcomes included the improvement of Positive and Negative Syndrome Scale scores, discontinuation because of adverse events, and individual adverse events.ResultsEighteen relevant studies were identified (total n=3,446; aripiprazole =267, blonanserin =285, clozapine =47, clocapramine =295, haloperidol =857, mosapramine =493, olanzapine =179, paliperidone =136, perospirone =146, placebo =138, quetiapine =212, and risperidone =338; mean study duration =8.33±1.41 weeks). In primary outcomes, olanzapine and paliperidone showed efficacy than placebo, and olanzapine and paliperidone showed superior acceptability compared with placebo. There were differences in the incidences of individual adverse events (the best antipsychotic: extrapyramidal symptoms = olanzapine, hyperprolactinemia- related symptoms = quetiapine, sedation = paliperidone, and weight change = blonanserin) among antipsychotics.ConclusionAlthough the current analysis exclusively included Japanese patients with schizophrenia, no remarkable differences were observed in efficacy and safety compared with previous meta-analyses. Diverse hierarchies in safety outcomes also support the implication that individual risk expectations for adverse events can guide clinical decisions. However, the sample size was relatively limited. Additional efficacy and safety data are required to fully obtain a conclusive understanding.

Efficacy, Tolerability, and Safety of Blonanserin in Schizophrenia: An Updated and Extended Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Blonanserin produced fewer cases of faintness/dizziness, psychomotor retardation, and diarrhea than did haloperidol. In our recent network meta-analysis evaluating the comparative efficacy and safety of antipsychotics for the treatment of Japanese patients with schizophrenia [6], blonanserin was the first-ranked antipsychotic for the lowest risk of weight change and was the second-lowest ranked antipsychotic for the risk of drowsiness, sedation, and somnolence. These findings are consistent with the results of previous meta-analyzes in which blonanserin exhibited a lower risk of weight gain than did risperidone and lower risk of dizziness than did haloperidol [3,5].…”

“…To identify relevant RCTs, an electronic search was conducted using Embase, Medline/PubMed, the Cochrane Library, the U.S. National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov), and the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; http://www.umin.ac.jp/ctr/ index.htm); the last search was performed on September 26, 2017, using the following search terms: "blonanserin" AND "schizophrenia" AND "random," "randomly," OR "randomized." Additional eligible RCTs were also sought through a manual search of reference lists from relevant articles and reviews [3,5,6].…”

“…Although dizziness and akathisia occur significantly less often with blonanserin than with haloperidol, blonanserin has a higher risk of akathisia than does risperidone [3]. Moreover, similar to aripiprazole, blonanserin produces less weight gain [2,[5][6][7]. Recently, 6 new randomized controlled trials (RCTs) have compared blonanserin with other antipsychotics [1,2,[8][9][10][11].…”

Evidence-based guidelines for the pharmacological treatment of schizophrenia: Updated recommendations from the British Association for Psychopharmacology

“…But when switching with the aim of enhancing therapeutic efficacy (Dold and Leucht, 2014), which antipsychotic medication should be chosen? Meta-analyses of RCTs reveal only modest differences in efficacy between the available non-clozapine antipsychotic medications and the clinical significance of any such small efficacy advantages is uncertain (Kishi et al, 2017a; Leucht et al, 2013).…”

Switching Antipsychotics to Blonanserin in Patients with Schizophrenia: An Open-label, Prospective, Multicenter Study

“…However, blonanserin induced less BW gain compared with risperidone. Furthermore, a recent network meta-analysis indicated that blonanserin was the most BW-neutral antipsychotic, with even less effect on BW than aripiprazole 33). As positive effects can be achieved when switching treatment from metabolically disruptive antipsychotics to more BW-neutral antipsychotics,27) the results of the present study suggest other benefits of switching to blonanserin from other antipsychotics that have a high to moderate risk of inducing metabolic abnormalities, including olanzapine, quetiapine, and risperidone.…”