Anti-dementia drugs for psychopathology and cognitive impairment in schizophrenia

A systematic review and meta-analysis

Taro Kishi, Toshikazu Ikuta, Kazuto Oya, Shinji Matsunaga, Yuki Matsuda, Nakao Iwata

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)748-757
Number of pages10
JournalInternational Journal of Neuropsychopharmacology
Volume21
Issue number8
DOIs
Publication statusPublished - 01-01-2018

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Psychopathology
Antipsychotic Agents
Dementia
Meta-Analysis
Schizophrenia
Pharmaceutical Preparations
Placebos
Rivastigmine
Cognition
Galantamine
Memantine
Brief Psychiatric Rating Scale
Verbal Learning
Cognitive Dysfunction
Executive Function
Therapeutics
Short-Term Memory
Anxiety
Randomized Controlled Trials
Learning

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

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. In: International Journal of Neuropsychopharmacology. 2018 ; Vol. 21, No. 8. pp. 748-757.
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title = "Anti-dementia drugs for psychopathology and cognitive impairment in schizophrenia: A systematic review and meta-analysis",
abstract = "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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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.

In: International Journal of Neuropsychopharmacology, Vol. 21, No. 8, 01.01.2018, p. 748-757.

Research output: Contribution to journalReview article

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

PY - 2018/1/1

Y1 - 2018/1/1

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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