Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: A 6‐week, randomized, double‐blind, placebo‐controlled study

Ishigooka, Jun; Iwashita, Shuichi; Tadori, Yoshihiro

doi:10.1111/pcn.12682

Cited by 52 publications

(51 citation statements)

References 14 publications

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“…Recently, a DBRCT of brexpiprazole for patients with acute schizophrenia as a Phase II/III study was conducted in Japan. 7 Surprisingly, this study found that brexpiprazole 2 mg/day, but not 4 mg/day, was superior to placebo for improvements in the PANSS total score and that neither brexpiprazole 4 nor 2 mg/day were superior to placebo for improvements in the PANSS positive subscale score and response rate. 7 On the basis of these findings, brexpiprazole 4 mg/day was not approved in Japan for the treatment of schizophrenia.…”

Section: Introductionmentioning

confidence: 57%

“…We did not retrieve any additional studies from the clinical trial registries ( Figure S1 ). Finally, three DBRCTs 4 , 5 , 7 were selected for inclusion. The total numbers of patients in the various arms were as follows: brexpiprazole 4 mg/day: n=477; brexpiprazole 2 mg/day: n=483; and placebo: n=484.…”

Section: Resultsmentioning

confidence: 99%

“…Although brexpiprazole 4 and 2 mg/day were both associated with a lower incidence of the discontinuation rate due to adverse events when compared with placebo, it was noted that the most common reasons for discontinuation due to adverse events were related to psychiatric problems such as schizophrenia. 4 , 5 , 7 …”

Section: Discussionmentioning

confidence: 99%

“…However, there were two notable differences in patient characteristics between the Japanese study 7 and the other two studies 4 , 5 ( Table 1 ). First, fewer patients were included in the Japanese study than in other studies, suggesting that the lack of statistical significance for some efficacy outcomes may have been a type II error resulting from the small sample size.…”

Section: Introductionmentioning

confidence: 96%

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Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials

Kishi¹,

Oya²,

Matsui³

et al. 2018

NDT

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PurposeThe purpose of this study was to compare the efficacy and safety of brexpiprazole 4 mg/day (B4) and 2 mg/day (B2) for treating acute schizophrenia.Patients and methodsWe performed three categorical meta-analyses (B4 vs placebo, B2 vs placebo, and B4 vs B2) of double-blind, randomized placebo-controlled trials (DBRCTs) that reported improvements in the Positive and Negative Syndrome Scale (PANSS) scores, response rate, Clinical Global Impression–Improvement and Severity (CGI-I and CGI-S) scores, discontinuation rate, and incidence of individual adverse events.ResultsWe identified three DBRCTs with 1,444 patients. Both B4 and B2 were superior to placebo for PANSS total score (B4: standardized mean difference [SMD] =−0.30, 95% CI =−0.43, −0.17; B2: SMD =−0.30, 95% CI =−0.46, −0.13), PANSS negative score, response rate, CGI-S score, and CGI-I score. B2, but not B4, was superior to placebo for the PANSS positive score. However, there was considerable heterogeneity in the meta-analysis for B4’s PANSS positive score, which disappeared after excluding a 2018 Japanese study from the meta-analysis that included more patients on a high-dose antipsychotic prior to their participation. A meta-analysis that excluded the data from the abovementioned patients showed B4 to be superior to the placebo in terms of the PANSS positive score (SMD =−0.22, 95% CI =−0.40, −0.03). B2, but not B4, was associated with a lower incidence of all-cause discontinuation compared with placebo. Both B4 and B2 were superior to placebo for discontinuation due to adverse events and schizophrenia, but both were associated with a higher incidence of weight gain compared with placebo. B4 was also associated with a higher risk of extrapyramidal symptoms than B2.ConclusionBoth B4 and B2 benefitted patients with schizophrenia, particularly those who were not previously on high-dose antipsychotics. Both the regimens were well-tolerated, but carried a risk of weight gain and extrapyramidal symptoms, although the latter risk was higher for B4 than B2.

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Section: Introductionmentioning

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials

Kishi¹,

Oya²,

Matsui³

et al. 2018

NDT

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Introduction The use of the blonanserin patch (BLO-P) for schizophrenia treatment was approved in Japan in 2019. This systematic review of trials in Japan assessed the efficacy and safety profile of BLO-P compared with other antipsychotics. Methods The systematic review included 6-week, double-blind, randomized, placebo-controlled, phase 3 trials in Japan that included patients with acute schizophrenia. Pooled data for patients receiving BLO-P 40 and 80 mg/day (BLO-P40+80) were compared with pooled data for patients receiving asenapine 10 and 20 mg/day (ASE10+20) and data for those receiving brexpiprazole 2 mg/day (BRE2) and paliperidone extended-release 6 mg/day (PAL-ER6). Results All the investigated treatments were superior to placebo in reducing the Positive and Negative Syndrome Scale (PANSS) total score; the Hedges’ g values (95% confidence interval) for BLO-P40+80, ASE10+20, BRE2, and PAL-ER6 were−0.40 (−0.58,−0.22),−0.61 (−0.79,−0.42),−0.33 (−0.60,−0.07), and−0.69 (−0.93,−0.45), respectively. There were differences among the antipsychotics in the incidence of various individual adverse events. Discussion BLO-P40+80 may have a good efficacy/safety/tolerability profile for the treatment of patients with acute schizophrenia.

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Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia

et al. 2021

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IMPORTANCEThe doses of antipsychotic drugs needed for relapse prevention in schizophrenia is a debated issue.OBJECTIVE To examine dose-response findings in a meta-analysis of randomized clinical trials.DATA SOURCES Studies were identified through the Cochrane Schizophrenia Group's Study-Based Register of Trials (March 9, 2020), PubMed (January 1, 2021), and previous reviews. First authors and/or pharmaceutical companies were contacted for additional information.STUDY SELECTION Two reviewers independently selected randomized clinical trials that compared fixed doses of a second-generation antipsychotic, haloperidol, or fluphenazine for relapse prevention in patients with stable schizophrenia. DATA EXTRACTION AND SYNTHESIS Using the Preferred Reporting Items for SystematicReviews and Meta-analyses guideline, all parameters in duplicate were extracted and frequentist dose-response random-effects meta-analyses were conducted.MAIN OUTCOMES AND MEASURES Study-defined relapse (primary outcome), rehospitalization, Positive and Negative Syndrome Scale or Brief Psychiatric Rating Scale total score reduction from baseline, all-cause discontinuation, and dropouts due to adverse events. RESULTSEvidence from 72 dose arms from 26 studies with 4776 participants was analyzed. The efficacy-related dose-response curves had a hyperbolic shape meaning that the probability to relapse decreased rapidly with doses of up to 5-mg/d risperidone equivalent (relative relapse risk, 0.43; 95% CI, 0.31-0.57; standardized mean difference for Positive and Negative Syndrome Scale total score reduction, −0.55; 95% CI, −0.68 to −0.41), but flattened thereafter. In contrast, dropouts due to adverse events continued to increase beyond this dose (relative risk at 5 mg/d, 1.38; 95% CI, 0.87-2.55; relative risk at 15 mg/d, 2.68; 95% CI, 1.49-4.62). In a subgroup analysis of patients in remission, a plateau was reached earlier, at approximately 2.5-mg/d risperidone equivalent. CONCLUSIONS AND RELEVANCEThe findings of this meta-analysis suggest that doses higher than approximately 5-mg/d risperidone equivalent may provide limited additional benefit for relapse prevention but more adverse events. For patients in remission or who are receiving high-potency first-generation antipsychotics, doses as low as 2.5-mg/d risperidone equivalent may be sufficient. However, caution is needed at this low dose end when further decreases of dose may be accompanied by a disproportionally higher relapse risk. Moreover, the observations are averages, and factors such as slow or rapid metabolism, age, illness stage, comorbidities, and drug-drug interactions suggest that individual patients will often need higher or lower doses.

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Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: A 6‐week, randomized, double‐blind, placebo‐controlled study

Abstract: Brexpiprazole was efficacious and well tolerated in Japanese adult patients with acute SCZ.

Cited by 52 publications

References 14 publications

Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials

Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia: a meta-analysis of double-blind, randomized placebo-controlled trials

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

Examination of Dosing of Antipsychotic Drugs for Relapse Prevention in Patients With Stable Schizophrenia

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