Anticholinergic Burden and Cognitive Function in Psychosis: A Systematic Review and Meta-Analysis

Objective: 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. Methods: 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 clinicalscales, serologicalanticholinergic activity, or tapering of anticholinergic medications. Analyses were carried out in R using the metafor 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). Results: 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), executivefunctions (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 executivefunctions (d= 0.44, 95% CI= 0.26, 0.62). Conclusions: 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.