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Do antipsychotics lead to cognitive impairment in dementia? A meta-analysis of randomised placebo-controlled trials

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Abstract

Behavioural and psychological symptoms in dementia (BPSD) are common and often treated with antipsychotics, which are known to have small efficacy and to cause many side effects. One potential side effect might be cognitive decline. We searched MEDLINE, Scopus, CENTRAL and www.ClincalStudyResult.org for randomized, double-blind, placebo-controlled trials using antipsychotics for treating BPSD and evaluated cognitive functioning. The studies identified were summarized in a meta-analysis with the standardized mean difference (SMD, Hedges’s g) as the effect size. Meta-regression was additionally performed to identify associated factors. Ten studies provided data on the course of cognitive functioning. The random effects model of the pooled analysis showed a not significant effect (SMD = −0.065, 95 % CI −0.186 to 0.057, I 2 = 41 %). Meta-regression revealed a significant correlation between cognitive impairment and treatment duration (R 2 = 0.78, p < 0.02) as well as baseline MMSE (R 2 = 0.92, p < 0.005). These correlations depend on only two out of ten studies and should interpret cautiously.

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Authors and Affiliations

  1. Department of Anaesthesiology, Intensive Care and Pain Medicine, Saarland University Medical Center, Homburg, Germany

    Alexander Wolf

  2. Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675, Munich, Germany

    Stefan Leucht & Frank-Gerald Pajonk

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  1. Alexander Wolf
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  2. Stefan Leucht
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  3. Frank-Gerald Pajonk
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Correspondence to Frank-Gerald Pajonk.

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Supplementary material 1 (DOCX 72 kb)

Supplemental figure 1 Funnel plot showing no significant publication bias (PPTX 58 kb)

406_2016_723_MOESM3_ESM.pptx

Supplemental figure 2 Forest plot of changes on cognitive course measured with MMSE and where available (in red colour) with ADAS-Cog during treatment as sensitivity analysis. Pooled and grouped analysis of second generation antipsychotics compared to placebo displayed as SMD. SMD: standardized mean difference, CI: confidence interval, RANDOM: random effects model (PPTX 62 kb)

406_2016_723_MOESM4_ESM.pptx

Supplemental figure 3 a,b Graphic processing of R2 and Variance regarding a) meta-regression correlating study length with cognitive change seen in figure 4 b) meta-regression correlating baseline MMSE with cognitive change seen in figure 5 (PPTX 76 kb)

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Wolf, A., Leucht, S. & Pajonk, FG. Do antipsychotics lead to cognitive impairment in dementia? A meta-analysis of randomised placebo-controlled trials. Eur Arch Psychiatry Clin Neurosci 267, 187–198 (2017). https://doi.org/10.1007/s00406-016-0723-4

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  • DOI: https://doi.org/10.1007/s00406-016-0723-4

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