TY - JOUR
T1 - Anti-dementia drugs for psychopathology and cognitive impairment in schizophrenia
T2 - A systematic review and meta-analysis
AU - Kishi, Taro
AU - Ikuta, Toshikazu
AU - Oya, Kazuto
AU - Matsunaga, Shinji
AU - Matsuda, Yuki
AU - Iwata, Nakao
N1 - Funding Information:
Drs Kishi, Ikuta, Oya, Matsunaga, Matsuda, and Iwata declare that they have no direct conflicts of interest relevant to this study. No grant support or other sources of funding were used to conduct this study or prepare this manuscript. Dr Kishi has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, and Tanabe-Mitsubishi (Yoshitomi) and has received a Health Labour Sciences research grant and a Fujita Health University School of Medicine research grant. Dr Ikuta has received speaker’s honoraria from Eli Lilly, Daiichi Sankyo, and Dainippon Sumitomo. Dr Oya has received speaker’s honoraria from Eisai, Eli Lilly, Janssen, Meiji, Otsuka, and Tanabe-Mitsubishi and has received a Fujita Health University School of Medicine research grant. Dr Matsunaga has received speaker’s honoraria from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Meiji, MSD, Novartis, Otsuka, and Tanabe-Mitsubishi and has received a Fujita Health University School of Medicine research grant and a grant-in-aid for young scientists (B). 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 Ikuta has received speaker’s honoraria from Eli Lilly, Daiichi Sankyo, and Dainippon Sumitomo. 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.
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of CINP.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Background: We conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of anti-dementia drugs plus antipsychotics for schizophrenia. Methods: Primary outcomes of efficacy and safety included improving overall symptoms (Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores) and all-cause discontinuation, respectively. Other outcomes included psychopathology subscales (positive, negative, general, and anxiety/depressive symptoms), cognitive function (attention/ vigilance, reasoning/problem solving, social cognition, speed of processing, verbal learning, visual learning, working memory, and cognitive control/executive function), Mini-Mental State Examination scores, treatment discontinuation due to adverse events and inefficacy, and individual adverse events. We evaluated the effect size using a random effects model. Results: We identified 37 studies (n=1574): 14 donepezil-based (n=568), 10 galantamine-based (n=371), 4 rivastigmine-based (n=146), and 9 memantine-based (n=489) studies. Pooled anti-dementia drugs plus antipsychotics treatments were superior to placebo plus antipsychotics in improving the overall symptoms (24 studies, 1069 patients: standardized mean difference=−0.34, 95% CI=−0.61 to −0.08, P=.01), negative symptoms (24 studies, 1077 patients: standardized mean difference =−0.62, 95% CI=−0.92 to −0.32, Pcorrected=.00018), and Mini-Mental State Examination scores (7 studies, 225 patients: standardized mean difference=−0.79, 95% CI=−1.23 to −0.34, P=.0006). No significant differences were found between antidementia drugs plus antipsychotics and placebo plus antipsychotics regarding other outcomes. Conclusions: Although the results suggest that anti-dementia drugs plus antipsychotics treatment improves negative symptoms and Mini-Mental State Examination scores in schizophrenia patients, they possibly were influenced by a small-study effect and some bias. However, it was not superior to placebo plus antipsychotics in improving composite cognitive test score, which more systematically evaluates cognitive impairment than the Mini-Mental State Examination score. Overall, the anti-dementia drugs plus antipsychotics treatment was well tolerated.
AB - Background: We conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of anti-dementia drugs plus antipsychotics for schizophrenia. Methods: Primary outcomes of efficacy and safety included improving overall symptoms (Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores) and all-cause discontinuation, respectively. Other outcomes included psychopathology subscales (positive, negative, general, and anxiety/depressive symptoms), cognitive function (attention/ vigilance, reasoning/problem solving, social cognition, speed of processing, verbal learning, visual learning, working memory, and cognitive control/executive function), Mini-Mental State Examination scores, treatment discontinuation due to adverse events and inefficacy, and individual adverse events. We evaluated the effect size using a random effects model. Results: We identified 37 studies (n=1574): 14 donepezil-based (n=568), 10 galantamine-based (n=371), 4 rivastigmine-based (n=146), and 9 memantine-based (n=489) studies. Pooled anti-dementia drugs plus antipsychotics treatments were superior to placebo plus antipsychotics in improving the overall symptoms (24 studies, 1069 patients: standardized mean difference=−0.34, 95% CI=−0.61 to −0.08, P=.01), negative symptoms (24 studies, 1077 patients: standardized mean difference =−0.62, 95% CI=−0.92 to −0.32, Pcorrected=.00018), and Mini-Mental State Examination scores (7 studies, 225 patients: standardized mean difference=−0.79, 95% CI=−1.23 to −0.34, P=.0006). No significant differences were found between antidementia drugs plus antipsychotics and placebo plus antipsychotics regarding other outcomes. Conclusions: Although the results suggest that anti-dementia drugs plus antipsychotics treatment improves negative symptoms and Mini-Mental State Examination scores in schizophrenia patients, they possibly were influenced by a small-study effect and some bias. However, it was not superior to placebo plus antipsychotics in improving composite cognitive test score, which more systematically evaluates cognitive impairment than the Mini-Mental State Examination score. Overall, the anti-dementia drugs plus antipsychotics treatment was well tolerated.
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U2 - 10.1093/ijnp/pyy045
DO - 10.1093/ijnp/pyy045
M3 - Review article
C2 - 29762677
AN - SCOPUS:85055432394
VL - 21
SP - 748
EP - 757
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 8
ER -