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

Taro Kishi, Kazuto Oya, Yuki Matsui, Ikuo Nomura, Kenji Sakuma, Makoto Okuya, Yuki Matsuda, Kiyoshi Fujita, Toshihiko Funahashi, Reiji Yoshimura, Nakao Iwata

Research output: Contribution to journalArticle

Abstract

Purpose: The 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 methods: We 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. Results: We 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. Conclusion: Both 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.

Original languageEnglish
Pages (from-to)2519-2530
Number of pages12
JournalNeuropsychiatric Disease and Treatment
Volume14
DOIs
Publication statusPublished - 01-01-2018

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Meta-Analysis
Schizophrenia
Randomized Controlled Trials
Placebos
Safety
Antipsychotic Agents
Weight Gain
Incidence
brexpiprazole

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Kishi, Taro ; Oya, Kazuto ; Matsui, Yuki ; Nomura, Ikuo ; Sakuma, Kenji ; Okuya, Makoto ; Matsuda, Yuki ; Fujita, Kiyoshi ; Funahashi, Toshihiko ; Yoshimura, Reiji ; Iwata, Nakao. / 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. In: Neuropsychiatric Disease and Treatment. 2018 ; Vol. 14. pp. 2519-2530.
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abstract = "Purpose: The 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 methods: We 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. Results: We 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. Conclusion: Both 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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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. / Kishi, Taro; Oya, Kazuto; Matsui, Yuki; Nomura, Ikuo; Sakuma, Kenji; Okuya, Makoto; Matsuda, Yuki; Fujita, Kiyoshi; Funahashi, Toshihiko; Yoshimura, Reiji; Iwata, Nakao.

In: Neuropsychiatric Disease and Treatment, Vol. 14, 01.01.2018, p. 2519-2530.

Research output: Contribution to journalArticle

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T1 - Comparison of the efficacy and safety of 4 and 2 mg/day brexpiprazole for acute schizophrenia

T2 - A meta-analysis of double-blind, randomized placebo-controlled trials

AU - Kishi, Taro

AU - Oya, Kazuto

AU - Matsui, Yuki

AU - Nomura, Ikuo

AU - Sakuma, Kenji

AU - Okuya, Makoto

AU - Matsuda, Yuki

AU - Fujita, Kiyoshi

AU - Funahashi, Toshihiko

AU - Yoshimura, Reiji

AU - Iwata, Nakao

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: The 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 methods: We 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. Results: We 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. Conclusion: Both 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.

AB - Purpose: The 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 methods: We 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. Results: We 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. Conclusion: Both 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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