Anticholinergic Burden and Cognitive Function in Psychosis: A Systematic Review and Meta-Analysis.
Scientific Abstract
The authors synthesized evidence from studies quantifying the relationship between anticholinergic medication and cognitive function in psychosis, and additionally explored studies that investigated whether reducing anticholinergic medications affects cognitive function in individuals with psychosis.
A database search was conducted in MEDLINE, Embase, and PsycINFO, from database inception to October 2023, for studies reporting objective cognitive assessment and quantification of anticholinergic burden using clinical scales, serological anticholinergic activity, or tapering of anticholinergic medications. Analyses were carried out in R using the package. Random-effects meta-analysis models were employed, along with assessment of heterogeneity, study quality, and meta-regressions (age, sex, and antipsychotic dosage in chlorpromazine equivalents).
Of 1,337 citations retrieved, 40 met inclusion criteria, comprising 25 anticholinergic burden studies (4,620 patients), six serological anticholinergic activity studies (382 patients), and nine tapering studies (186 patients). A negative correlation was identified between anticholinergic burden and global cognition (r=-0.37, 95% CI=-0.48, -0.25), verbal learning (r=-0.28, 95% CI=-0.36, -0.21), visual learning (r=-0.17, 95% CI=-0.28, -0.06), working memory (r=-0.22, 95% CI=-0.29, -0.14), processing speed (r=-0.24, 95% CI=-0.35, -0.13), attention (r=-0.19, 95% CI=-0.29, -0.08), executive functions (r=-0.17, 95% CI=-0.27, -0.06), and social cognition (r=-0.12, 95% CI=-0.19, -0.05), and between serological anticholinergic activity and verbal learning (r=-0.26, 95% CI=-0.38, -0.14), working memory (r=-0.19, 95% CI=-0.35, -0.03), and executive functions (r=-0.16, 95% CI=-0.27, -0.04). Finally, tapering off anticholinergic medication improved the scores in verbal learning (d=0.77, 95% CI=0.44, 1.1), working memory (d=0.94, 95% CI=0.63, 1.26), and executive functions (d=0.44, 95% CI=0.26, 0.62).
Anticholinergic burden is associated with the cognitive impairments observed in psychosis. From a clinical perspective, tapering off anticholinergic medication in patients with psychosis may improve cognition. However, randomized clinical trials are needed for an unbiased quantification of benefit.
Similar content
News
Dr Jeffrey Stedehouder awarded Cambridge NeuroWorks Blue Sky Proof-of-Concept Award
16 September 2026
Paper
MRC CoRE in RND Output
The hippocampus as a generative model.
2026. Philos Trans R Soc Lond B Biol Sci, 381(1954).
Free Full Text at Europe PMC
PMC7619457
Preprint
Phase-targeted modulation of essential tremor with transcranial magnetic stimulation of motor cortex
Preprint
Driving theta-gamma oscillations modulates extrasynaptic GABAergic tone: a tACS-TMS study
Anticholinergic Burden and Cognitive Function in Psychosis: A Systematic Review and Meta-Analysis.
Scientific Abstract
The authors synthesized evidence from studies quantifying the relationship between anticholinergic medication and cognitive function in psychosis, and additionally explored studies that investigated whether reducing anticholinergic medications affects cognitive function in individuals with psychosis.
A database search was conducted in MEDLINE, Embase, and PsycINFO, from database inception to October 2023, for studies reporting objective cognitive assessment and quantification of anticholinergic burden using clinical scales, serological anticholinergic activity, or tapering of anticholinergic medications. Analyses were carried out in R using the package. Random-effects meta-analysis models were employed, along with assessment of heterogeneity, study quality, and meta-regressions (age, sex, and antipsychotic dosage in chlorpromazine equivalents).
Of 1,337 citations retrieved, 40 met inclusion criteria, comprising 25 anticholinergic burden studies (4,620 patients), six serological anticholinergic activity studies (382 patients), and nine tapering studies (186 patients). A negative correlation was identified between anticholinergic burden and global cognition (r=-0.37, 95% CI=-0.48, -0.25), verbal learning (r=-0.28, 95% CI=-0.36, -0.21), visual learning (r=-0.17, 95% CI=-0.28, -0.06), working memory (r=-0.22, 95% CI=-0.29, -0.14), processing speed (r=-0.24, 95% CI=-0.35, -0.13), attention (r=-0.19, 95% CI=-0.29, -0.08), executive functions (r=-0.17, 95% CI=-0.27, -0.06), and social cognition (r=-0.12, 95% CI=-0.19, -0.05), and between serological anticholinergic activity and verbal learning (r=-0.26, 95% CI=-0.38, -0.14), working memory (r=-0.19, 95% CI=-0.35, -0.03), and executive functions (r=-0.16, 95% CI=-0.27, -0.04). Finally, tapering off anticholinergic medication improved the scores in verbal learning (d=0.77, 95% CI=0.44, 1.1), working memory (d=0.94, 95% CI=0.63, 1.26), and executive functions (d=0.44, 95% CI=0.26, 0.62).
Anticholinergic burden is associated with the cognitive impairments observed in psychosis. From a clinical perspective, tapering off anticholinergic medication in patients with psychosis may improve cognition. However, randomized clinical trials are needed for an unbiased quantification of benefit.
Citation
2025. Am J Psychiatry, 182(4):349-359.
DOI
10.1176/appi.ajp.20240260
Downloads
Similar content
News
Dr Jeffrey Stedehouder awarded Cambridge NeuroWorks Blue Sky Proof-of-Concept Award
16 September 2026
Paper
MRC CoRE in RND Output
The hippocampus as a generative model.
2026. Philos Trans R Soc Lond B Biol Sci, 381(1954).
Free Full Text at Europe PMC
PMC7619457
Preprint
Phase-targeted modulation of essential tremor with transcranial magnetic stimulation of motor cortex
Preprint