Blonanserin versus haloperidol in Japanese patients with schizophrenia: A phase 3, 8‐week, double‐blind, multicenter, randomized controlled study

Abstract

Objective This Japanese, multicenter, randomized, double‐blind trial, evaluating the efficacy and safety of blonanserin compared with haloperidol in patients with schizophrenia, was previously published by Murasaki in the Japanese language. In this article, we present the results of the trial based on full analysis dataset instead of per protocol dataset formerly reported and discuss the findings in light of the latest knowledge of pharmacological treatment for schizophrenia. Methods A total of 265 patients were randomized to receive blonanserin (8 to 24 mg/d) or haloperidol (4 to 12 mg/d) twice daily for 8 weeks. Efficacy assessments included the Clinical Global Impressions—Improvement (CGI‐I) and the Positive and Negative Syndrome Scale (PANSS). Results Blonanserin was not inferior to haloperidol with a margin of 10% with respect to the improvement rate on CGI‐I at end of study (60.5% vs 50.0%, P < 0.001). The decrease in the PANSS total score did not differ between the drugs (−10.3 vs −7.1). For the PANSS negative symptom score, the decrease was significantly greater with blonanserin than with haloperidol (P = 0.006). Blonanserin was well tolerated. The incidence of adverse events was similar for the two drugs. Extrapyramidal adverse events, sedation, hypotension, and prolactin increase were rarer with blonanserin than with haloperidol. No clinically important weight gain was observed. Conclusions Blonanserin is as effective as haloperidol for the treatment of schizophrenia. Blonanserin is more effective for negative symptoms with a lower risk of extrapyramidal symptoms compared with haloperidol.

Blonanserin vs risperidone in Japanese patients with schizophrenia: A post hoc analysis of a phase 3, 8‐week, multicenter, double‐blind, randomized controlled study

“…Blonanserin was reportedly more effective to negative symptoms than haloperidol . The recent meta‐analysis indicated that blonanserin has potentially superior efficacy in negative symptoms to other SGAs .…”

“…Due to its receptor‐binding profiles, blonanserin is expected to improve positive and negative symptoms, while suppressing extrapyramidal side effects that were a serious problem in FGAs. Previous reports on randomized controlled trials showed similar efficacy of blonanserin in various psychiatric symptoms in schizophrenia compared with haloperidol or risperidone …”

“…Blinding was maintained with a double‐dummy design. Blonanserin was administered as 2‐ or 4‐mg tablet, started from 8 mg/d, and could be adjusted thereafter between 8 and 24 mg/d, which was the same manner as that in the preceding haloperidol‐controlled study . Risperidone was given as 1‐ or 2‐mg tablet, started from 2 mg/d and could be adjusted thereafter between 2 and 6 mg/d according to the agreement made with Japanese authority .…”

“…Laboratory data, vital signs, weight, ECG parameters, and EEG parameters were analyzed for change from baseline and the incidence of abnormal change by treatment group and evaluation point. The intergroup difference in the change in PANSS total score of 0 and a standard deviation of 20 was assumed . A total of 260 patients (130 per group) were required to provide a power of 80% to establish noninferiority.…”

“…Previous reports on randomized controlled trials showed similar efficacy of blonanserin in various psychiatric symptoms in schizophrenia compared with haloperidol or risperidone. 5,6 The comparator, risperidone, is one of the most widely used SGAs. It has high affinity for serotonin 5-HT 2A and 5-HT 7 , dopamine D 2 , adrenergic α 1 and α 2 receptors and a moderate affinity for histamine H 1 receptors.…”