Dataset Information

Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis.

ABSTRACT:

Background

Cognitive impairment in schizophrenia is disabling, but current treatment options remain limited.

Objective

To meta-analyze the efficacy and safety of adjunctive antidepressants for cognitive impairment in schizophrenia.

Data sources and study selection

PubMed, 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 extraction

Two 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.

Results

We 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).

Conclusion

Adjunctive 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.

SUBMITTER: Vernon JA

PROVIDER: S-EPMC4252251 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis.

Vernon Jeffrey A JA Grudnikoff Eugene E Seidman Andrew J AJ Frazier Thomas W TW Vemulapalli Mani Sandhya MS Pareek Priyanki P Goldberg Terry E TE Kane John M JM Correll Christoph U CU

Schizophrenia research 20140918 2-3

<h4>Background</h4>Cognitive impairment in schizophrenia is disabling, but current treatment options remain limited.<h4>Objective</h4>To meta-analyze the efficacy and safety of adjunctive antidepressants for cognitive impairment in schizophrenia.<h4>Data sources and study selection</h4>PubMed, 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 cogn ...[more]

PMID: 25240772

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Project 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, 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.

Project description:ImportanceSchizophrenia is associated with cognitive dysfunction and cardiovascular risk factors, including metabolic syndrome (MetS) and its constituent criteria. Cognitive dysfunction and cardiovascular risk factors can worsen cognition in the general population and may contribute to cognitive impairment in schizophrenia.ObjectiveTo study the association between cognitive dysfunction and cardiovascular risk factors and cognitive impairment in individuals with schizophrenia.Data sourcesA search was conducted of Embase, Scopus, MEDLINE, PubMed, and Cochrane databases from inception to February 25, 2020, using terms that included synonyms of schizophrenia AND metabolic adversities AND cognitive function. Conference proceedings, clinical trial registries, and reference lists of relevant publications were also searched.Study selectionStudies were included that (1) examined cognitive functioning in patients with schizophrenia or schizoaffective disorder; (2) investigated the association of cardiovascular disease risk factors, including MetS, diabetes, obesity, overweight, obesity or overweight, hypertension, dyslipidemia, and insulin resistance with outcomes; and (3) compared cognitive performance of patients with schizophrenia/schizoaffective disorder between those with vs without cardiovascular disease risk factors.Data extraction and synthesisExtraction of data was conducted by 2 to 3 independent reviewers per article. Data were meta-analyzed using a random-effects model.Main outcomes and measuresThe primary outcome was global cognition, defined as a test score using clinically validated measures of overall cognitive functioning.ResultsTwenty-seven studies involving 10 174 individuals with schizophrenia were included. Significantly greater global cognitive deficits were present in patients with schizophrenia who had MetS (13 studies; n = 2800; effect size [ES] = 0.31; 95% CI, 0.13-0.50; P = .001), diabetes (8 studies; n = 2976; ES = 0.32; 95% CI, 0.23-0.42; P < .001), or hypertension (5 studies; n = 1899; ES = 0.21; 95% CI, 0.11-0.31; P < .001); nonsignificantly greater deficits were present in patients with obesity (8 studies; n = 2779; P = .20), overweight (8 studies; n = 2825; P = .41), and insulin resistance (1 study; n = 193; P = .18). Worse performance in specific cognitive domains was associated with cognitive dysfunction and cardiovascular risk factors regarding 5 domains in patients with diabetes (ES range, 0.23 [95% CI, 0.12-0.33] to 0.40 [95% CI, 0.20-0.61]) and 4 domains with MetS (ES range, 0.15 [95% CI, 0.03-0.28] to 0.40 [95% CI, 0.20-0.61]) and hypertension (ES range, 0.15 [95% CI, 0.04-0.26] to 0.27 [95% CI, 0.15-0.39]).Conclusions and relevanceIn this systematic review and meta-analysis, MetS, diabetes, and hypertension were significantly associated with global cognitive impairment in people with schizophrenia.

Project description:BackgroundThe effectiveness of treatments for mild cognitive impairment is uncertain. The aim of this review was to evaluate the effectiveness and harms of treatment for mild cognitive impairment in adults 65 years of age and older.MethodsWe searched MEDLINE, Embase and Cochrane Central (December 2012-December 2014); citations from 2 systematic reviews were considered for inclusion. We included randomized controlled trials involving community-dwelling adults aged 65 years and older with a diagnosis of mild cognitive impairment. Studies reporting on cognition, function, behaviour, global status, mortality and adverse events for treatment with pharmacologic and nonpharmacologic interventions were included.ResultsSeventeen studies were included. Cholinesterase inhibitor studies evaluating cognition (Alzheimer's Disease Assessment Scale, cognition subscale) showed no difference between intervention and control groups (mean difference [MD] -0.33, 95% CI -0.73 to 0.06]; one behavioural study showed no significant effect on cognition (Alzheimer's Disease Assessment Scale, cognition subscale) for the intervention group when compared to controls (MD -0.60, (95% CI -1.44 to 0.24), and one study on vitamin E showed no difference between intervention and control groups (MD 0.85, 95% CI -0.32 to 2.02). With the Mini-Mental State Examination, cholinesterase inhibitors showed no difference between intervention and control groups (MD 0.17, 95% CI -0.13 to 0.47); behavioural studies showed a significant difference favouring intervention (MD 1.01, 95% CI 0.25 to 1.77), and studies of dietary supplements and/or vitamins showed no difference between intervention and control groups (MD 0.20, 95% CI -0.04 to 0.43). Pharmacologic studies showed no difference in serious adverse events (risk ratio 0.98, 95% CI 0.86 to 1.10). No serious adverse events were reported for nonpharmacologic interventions.InterpretationTreatment of mild cognitive impairment with cholinesterase inhibitors showed no benefit when compared with a control group. A small cognitive benefit was observed using behavioural therapies when compared with the control group. However, the clinical significance of this small benefit remains uncertain. The current evidence does not support the use of cholinesterase inhibitors for treating mild cognitive impairment, and future high-quality research using a standardized approach is needed to affirm the finding of a small benefit on cognition that was observed for behavioural interventions.RegistrationPROSPERO no. CRD42014015431.

Dataset Information

Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis.

Background

Objective

Data sources and study selection

Data extraction

Results

Conclusion

Publications

Antidepressants for cognitive impairment in schizophrenia--a systematic review and meta-analysis.

Similar Datasets

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