Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment in schizophrenia: results from the multicenter FACE-SZ cohort

Nathan Vidal; Paul Roux; Mathieu Urbach; Cristobal Belmonte; Laurent Boyer; Delphine Capdevielle; Julie Clauss-Kobayashi; Thierry D'Amato; Romane Dassing; Caroline Dubertret; Julien Dubreucq; Guillaume Fond; Roxana-Mihaela Honciuc; Sylvain Leignier; Pierre-Michel Llorca; Jasmina Mallet; David Misdrahi; Baptiste Pignon; Romain Rey; Franck Schürhoff; Arnaud Tessier; FACE-SZ (FondaMental Academic Centers of Expertise—Schizophrenia) Group; Christine Passerieux; Eric Brunet-Gouet

doi:10.3389/fphar.2024.1403093

Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment in schizophrenia: results from the multicenter FACE-SZ cohort

Front Pharmacol. 2024 Jun 12:15:1403093. doi: 10.3389/fphar.2024.1403093. eCollection 2024.

Authors

Nathan Vidal^{1

2}, Paul Roux^{1

2}, Mathieu Urbach^{1

2}, Cristobal Belmonte^{1

3}, Laurent Boyer^{1

4}, Delphine Capdevielle^{1

3

5}, Julie Clauss-Kobayashi^{1

6}, Thierry D'Amato^{1

7}, Romane Dassing^{1

6}, Caroline Dubertret^{1

8}, Julien Dubreucq^{1

9}, Guillaume Fond^{1

4}, Roxana-Mihaela Honciuc^{1

10}, Sylvain Leignier^{1

9}, Pierre-Michel Llorca^{1

10}, Jasmina Mallet^{1

8}, David Misdrahi^{1

11}, Baptiste Pignon^{1

12}, Romain Rey^{1

7}, Franck Schürhoff^{1

12}, Arnaud Tessier^{1

11}; FACE-SZ (FondaMental Academic Centers of Expertise—Schizophrenia) Group; Christine Passerieux^{1

2}, Eric Brunet-Gouet^{1

2}

Collaborators

FACE-SZ (FondaMental Academic Centers of Expertise—Schizophrenia) Group:
B Aouizerate, V Barteau, S Bensalem, F Berna, O Blanc, E Bourguignon, L Boyer, D CapdevielleI Chéreau, G Chesnoy-Servanin, T D'Amato, A Deloge, H Denizot, J M Dorey, C Dubertret, J Dubreucq, S Esselin, C Faget, C Fluttaz, G Fond, F Gabayet, O Godin, E Haffen, R M Honciuc, M Jarroir, D Lacelle, C Lançon, H Laouamri, M Leboyer, P M Llorca, J Mallet, E Metairie, D Misdrahi, C Passerieux, J Petrucci, P Peri, B Pignon, S Pires, C Portalier, R Rey, C Roman, F Schürhoff, K Souryis, A Szöke, M Urbach, F Vaillant, A, Vehier, P Vidailhet, E Vilà, G Wahiche, H Yazbek, A Zinetti-Bertschy

Affiliations

¹ FondaMental Foundation, Créteil, France.
² Centre Hospitalier de Versailles, Service universitaire de psychiatrie d'adultes et d'addictologie, Le Chesnay, Université Paris-Saclay, Université de Versailles Saint-Quentin-En-Yvelines, DisAP-DevPsy-CESP, Institut National de la Santé et de la Recherche Médicale (INSERM), Villejuif, France.
³ University Department of Adult Psychiatry, Hospital La Colombière, CHU Montpellier, Montpellier, France.
⁴ EA 3279: Department of Epidemiology and Health Economics, School of Medicine-La Timone Medical Campus, Marseille University Hospital, Aix-Marseille University, Marseille, France.
⁵ Institute of Functional Genomics, University of Montpellier, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Montpellier, France.
⁶ Department of Psychiatry, University Hospitals of Strasbourg, University of Strasbourg, Institut National de la Santé et de la Recherche Médicale (INSERM), Strasbourg, France.
⁷ Le Vinatier Hospital, Schizophrenia Expert Centre, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), University Lyon 1, Lyon Neuroscience Research Center, PSYR2 Team, Lyon, France.
⁸ Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Psychiatry, Louis Mourier Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Psychiatry and Neuroscience of Paris, University Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Paris, France.
⁹ Grenoble Alpes University, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble Alpes, Grenoble Institute of Neurosciences, Grenoble, France.
¹⁰ CHU Clermont-Ferrand, Service of psychiatry B, University of Clermont Auvergne, Clermont-Ferrand, France.
¹¹ Department of Universitary and General Psychiatry, Charles Perrens Hospital, University of Bordeaux, Aquitaine Institute for Cognitive and Integrative Neuroscience (CNRS UMR 5287-INCIA, ECOPSY), Bordeaux, France.
¹² Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires "H. Mondor", DMU IMPACT, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Médicale (IMRB), Translational Neuropsychiatry, University Paris-Est-Créteil (UPEC), Créteil, France.

Abstract

Aim: The anticholinergic properties of medications are associated with poorer cognitive performance in schizophrenia. Numerous scales have been developed to assess anticholinergic burden and yet, there is no consensus indicating which anticholinergic burden scale is more relevant for patients with schizophrenia. We aimed to identify valid scales for estimating the risk of iatrogenic cognitive impairment in schizophrenia.

Methods: We identified 27 scales in a literature review. The responses to neuropsychological tests of 839 individuals with schizophrenia or schizoaffective disorder in the FACE-SZ database were collected between 2010 and 2021. We estimated the association between objective global cognitive performance and the 27 scales, the number of psychotropic drugs, and chlorpromazine and lorazepam equivalents in bivariable regressions in a cross-sectional design. We then adjusted the bivariable models with covariates: the predictors significantly associated with cognitive performance in multiple linear regressions were considered to have good concurrent validity to assess cognitive performance.

Results: Eight scales, the number of psychotropic drugs, and drug equivalents were significantly associated with cognitive impairment. The number of psychotropic drugs, the most convenient predictor to compute, was associated with worse executive function (Standardized β = -0.12, p = .004) and reasoning (Standardized β = -0.08, p = .037).

Conclusion: Anticholinergic burden, the number of psychotropic drugs, and drug equivalents were weakly associated with cognition, thus suggesting that cognitive impairment in schizophrenia and schizoaffective disorder is explained by factors other than medication. The number of psychotropic drugs was the most parsimonious method to assess the risk of iatrogenic cognitive impairment.

Keywords: cholinergic antagonist; neuropsychological test; polypharmacy; psychotropic drug; schizophrenia.

Copyright © 2024 Vidal, Roux, Urbach, Belmonte, Boyer, Capdevielle, Clauss-Kobayashi, D’Amato, Dassing, Dubertret, Dubreucq, Fond, Honciuc, Leignier, Llorca, Mallet, Misdrahi, Pignon, Rey, Schürhoff, Tessier, the FACE-SZ (FondaMental Academic Centers of Expertise—Schizophrenia) Group, Passerieux and Brunet-Gouet.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by a grant from the Centre Hospitalier de Versailles (Bourse Registre 2019), by the Fondation FondaMental, Créteil, France and the Investissements d'Avenir programs managed by the ANR under references ANR-11-IDEX-0004-02 and ANR-10-COHO-10-01.