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Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis

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 Sca...

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Autores principales: Kishi, Taro, Ikuta, Toshikazu, Oya, Kazuto, Matsunaga, Shinji, Matsuda, Yuki, Iwata, Nakao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070030/
https://www.ncbi.nlm.nih.gov/pubmed/29762677
http://dx.doi.org/10.1093/ijnp/pyy045
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author Kishi, Taro
Ikuta, Toshikazu
Oya, Kazuto
Matsunaga, Shinji
Matsuda, Yuki
Iwata, Nakao
author_facet Kishi, Taro
Ikuta, Toshikazu
Oya, Kazuto
Matsunaga, Shinji
Matsuda, Yuki
Iwata, Nakao
author_sort Kishi, Taro
collection PubMed
description 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, P(corrected)=.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 anti-dementia 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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spelling pubmed-60700302018-08-08 Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis Kishi, Taro Ikuta, Toshikazu Oya, Kazuto Matsunaga, Shinji Matsuda, Yuki Iwata, Nakao Int J Neuropsychopharmacol Review 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, P(corrected)=.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 anti-dementia 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. Oxford University Press 2018-05-14 /pmc/articles/PMC6070030/ /pubmed/29762677 http://dx.doi.org/10.1093/ijnp/pyy045 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of CINP. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Review
Kishi, Taro
Ikuta, Toshikazu
Oya, Kazuto
Matsunaga, Shinji
Matsuda, Yuki
Iwata, Nakao
Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis
title Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis
title_full Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis
title_fullStr Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis
title_full_unstemmed Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis
title_short Anti-Dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-Analysis
title_sort anti-dementia drugs for psychopathology and cognitive impairment in schizophrenia: a systematic review and meta-analysis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070030/
https://www.ncbi.nlm.nih.gov/pubmed/29762677
http://dx.doi.org/10.1093/ijnp/pyy045
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