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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 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.

SUBMITTER: Kishi T

PROVIDER: S-EPMC6070030 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Kishi Taro T Ikuta Toshikazu T Oya Kazuto K Matsunaga Shinji S Matsuda Yuki Y Iwata Nakao N

The international journal of neuropsychopharmacology 20180801 8

<h4>Background</h4>We conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of anti-dementia drugs plus antipsychotics for schizophrenia.<h4>Methods</h4>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/depr ...[more]

PMID: 29762677

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Project description:BackgroundCognitive impairment in schizophrenia is disabling, but current treatment options remain limited.ObjectiveTo meta-analyze the efficacy and safety of adjunctive antidepressants for cognitive impairment in schizophrenia.Data sources and study selectionPubMed, MEDLINE, PsycINFO, and Cochrane Library databases were searched until 12/2013 for randomized controlled trials comparing antidepressant augmentation of antipsychotics with placebo regarding effects on cognitive functioning in schizophrenia.Data extractionTwo authors independently extracted data. Standardized mean differences (SMDs) were calculated for continuous outcomes and risk ratios for categorical outcomes. SMDs of individual cognitive tests were pooled on a study level within domains (primary outcome) and across domains. When results were heterogeneous, random instead of fixed effects models were used.ResultsWe meta-analyzed 11 studies (duration = 8.7 ± 3.7 weeks) including 568 patients (mean age = 39.5 ± 6.9 years, males = 67.2%, illness duration = 12.5 ± 8.0 years). Antidepressants included mirtazapine (4 studies; n = 126), citalopram (2 studies; n = 231), fluvoxamine (1 study; n = 47), duloxetine (1 study; n = 40), mianserin (1 study; n = 30), bupropion (1 study; n = 61), and reboxetine (1 study; n = 33). Statistically significant, but clinically negligible, advantages were found for pooled antidepressants compared to placebo in executive function (Hedges' g = 0.17, p = 0.02) and a composite cognition score (Hedges' g = 0.095, p = 0.012). Depression improved with serotonergic antidepressants (p = 0.0009) and selective serotonin reuptake inhibitors (p = 0.009), but not with pooled antidepressants (p = 0.39). Sedation was more common with pooled antidepressants (p = 0.04).ConclusionAdjunctive antidepressants do not demonstrate clinically significant effects on cognition in schizophrenia patients, however, larger studies, preferably in euthymic schizophrenia patients and using full neurocognitive batteries, are needed to confirm this finding.

Project description:BackgroundThere is growing evidence that sepsis survivors are at increased risk of developing new-onset atrial fibrillation, acute kidney injury, and neurological diseases. However, whether sepsis survivals increase the risk of dementia or cognitive impairment remains to be further explored.ObjectiveThe objective of this study was to determine whether sepsis survivals increase the risk of dementia or cognitive impairment.MethodsWe searched PubMed, Cochrane Library, Web of Science, and EMBASE databases for cohort studies or case-control studies from their inception to November 5, 2021. The quality of this study was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). The Stata software (version 15.1) was used to calculate the odds ratio (OR) of dementia or cognitive impairment in sepsis survivals. Subgroup and sensitivity analyses were performed to assess the source of heterogeneity. Funnel plots and Egger's test were used to detect the publication bias.ResultsEight studies (i.e., seven cohort studies and one case-control study) involving 891,562 individuals were included. The quality assessment results showed that the average score of NOS was over 7, and the overall quality of the included studies was high. Pooled analyses indicated that sepsis survivals were associated with an increased risk of all-cause dementia (OR = 1.62, 95% CI = 1.23-2.15, I 2 = 96.4%, p = 0.001). However, there was no obvious association between sepsis survivals and the risk of cognitive impairment (OR = 1.77, 95% CI = 0.59-5.32, I 2 = 87.4%, p = 0.306). Subgroup analyses showed that severe sepsis was associated with an increased risk of dementia or cognitive impairment (OR = 1.99, 95% CI = 1.19-3.31, I 2 = 75.3%, p = 0.008); such risk was higher than that of other unspecified types of sepsis (OR = 1.47, 95% CI = 1.04-2.09, I 2 = 97.6%, p = 0.029).ConclusionSepsis survivals are associated with an increased risk of all-cause dementia but not with cognitive impairment. Appropriate management and prevention are essential to preserve the cognitive function of sepsis survivors and reduce the risk of dementia.

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Dataset Information

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

Publications

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

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