TY - JOUR
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
N1 - Funding Information:
Dr Kishi has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, Yoshitomi, and Tanabe-Mitsubishi and has received a Health Labour Sciences Research Grant and a Fujita Health University School of Medicine research grant. Dr Oya has received speaker’s honoraria from Chugai, Dainippon Sumitomo, Eisai, Eli Lilly, Janssen, Kissei, Meiji, MSD, Otsuka, and Tanabe-Mitsubishi and has received a Fujita Health University School of Medicine research grant. Dr Matsui has received speaker’s honoraria from Dainippon Sumitomo and Otsuka and has received a Fujita Health University School of Medicine research grant. Dr Nomura has received speaker’s honoraria from Meiji, MSD, and Otsuka. Dr Okuya has received speaker’s honoraria from Meiji. Dr Matsuda has received speaker’s honoraria from Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Otsuka, Tanabe-Mitsubishi, and Pfizer and has received a grant-in-aid for Young Scientists (B). Dr Fujita has received speaker’s honoraria from Dainippon Sumitomo, Eli Lilly, Janssen, Otsuka, Meiji, Novartis, and Pfizer. Dr Yoshimura has received speaker’s honoraria from Dainippon Sumitomo, Eli Lilly, Otsuka, and Meiji. Dr Iwata has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Yoshitomi, Otsuka, Meiji, Shionogi, Novartis, and Pfizer and has had research grants from GlaxoSmithKline, Meiji, and Otsuka. The authors report no other conflicts of interest in this work.
Publisher Copyright:
© 2018 Kishi et al.
PY - 2018
Y1 - 2018
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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U2 - 10.2147/NDT.S176676
DO - 10.2147/NDT.S176676
M3 - Article
AN - SCOPUS:85057566511
VL - 14
SP - 2519
EP - 2530
JO - Neuropsychiatric Disease and Treatment
JF - Neuropsychiatric Disease and Treatment
SN - 1176-6328
ER -