Anticholinergic Activity of Psychotropic Drugs and Cognitive Impairment Among Participants Aged 45 and Over: The CONSTANCES Study

Abdelkrim Ziad (), Claudine Berr (), Fabrice Ruiz (), Bernard Bégaud (), Cédric Lemogne (), Marcel Goldberg (), Marie Zins () and Thibault Mura ()
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Abdelkrim Ziad: ClinSearch-110
Claudine Berr: INSERM, University of Montpellier, U1061, Neuropsychiatry: Epidemiological and Clinical Research
Fabrice Ruiz: ClinSearch-110
Bernard Bégaud: INSERM, U1219-Pharmacoepidemiology, Bordeaux University
Cédric Lemogne: Université de Paris, Faculté de Santé, UFR de Médecine
Marcel Goldberg: Population-based Epidemiological Cohorts Unit, US 011 Inserm
Marie Zins: Population-based Epidemiological Cohorts Unit, US 011 Inserm
Thibault Mura: INSERM, University of Montpellier, U1061, Neuropsychiatry: Epidemiological and Clinical Research

Drug Safety, 2021, vol. 44, issue 5, No 6, 565-579

Abstract: Abstract Introduction Psychotropic drugs such as anxiolytics, antidepressants and antipsychotics may have anticholinergic properties that could directly affect patients’ cognition. Objectives Our objective was to assess the relationship between exposure to anticholinergic-positive (AC+) psychotropic drugs and cognitive impairment compared with psychotropic drugs without anticholinergic activity (AC−). Methods This analysis included participants (aged 45–70 years) enrolled between January 2012 and October 2017 in the CONSTANCES cohort treated with psychotropic drugs (antidepressants n = 2602, anxiolytics n = 1195, antipsychotics n = 197) in the 3 years preceding cognitive assessment. Within each drug class, the Anticholinergic Cognitive Burden scale was used to classify drugs as either AC+ or AC−. Cognitive impairment was defined as a score below − 1 standard deviation from the standardized mean of the neuropsychological score. We used multiple logistic regression models and matching on propensity score to estimate the relationship between anticholinergic activity and cognitive impairment. Results Our analyses did not show any increased risk of cognitive impairment for AC+ antidepressants and anxiolytics, with the exception of a slight increase for AC+ antidepressants in episodic memory (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.05–1.36). Conversely, we found a more marked increase in risk with AC+ antipsychotics on executive function (Trail Making Test-A [TMT-A], OR 4.49 [95% CI 2.59–7.97] and TMT-B, OR 3.62 [95% CI 2.25–5.89]). Conclusion Our results suggest there is no clinically relevant association between the anticholinergic activity of antidepressant and anxiolytic drugs and cognitive impairment in middle-aged adults. An association could exist between AC+ antipsychotics and executive function.

Date: 2021
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DOI: 10.1007/s40264-021-01043-5

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