Guillaume Fond1,2,3,4, F Berna5,6, L Boyer5,7, O Godin5,8, L Brunel5,9, M Andrianarisoa5,9, B Aouizerate5,10,11, D Capdevielle5,12, I Chereau5,13, J M Danion5,6, C Dubertret5,14, J Dubreucq5,15, C Faget5,16, F Gabayet5,15, T Le Gloahec5,9, P M Llorca5,13, J Mallet5,14, D Misdrahi5,10,17, R Rey5,18, R Richieri5,16, C Passerieux5,19, C Portalier5,14, P Roux5,19, A Vehier5,18, H Yazbek5,12, F Schürhoff5,9, E Bulzacka5,9. 1. Fondation FondaMental, Créteil, France. guillaume.fond@gmail.com. 2. INSERM U955, Translational Psychiatry Team, DHU Pe-PSY, Centre Expert Schizophrénie, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires Henri Mondor,, Paris Est University, 40 rue de Mesly, 94000, Créteil, France. guillaume.fond@gmail.com. 3. Clinique Jeanne d'arc-Hôpital Privé Parisien, 55 rue du commandant Mouchotte, 94160, Saint-Mandé, France. guillaume.fond@gmail.com. 4. CHU Carémeau, 30000, Nîmes, France. guillaume.fond@gmail.com. 5. Fondation FondaMental, Créteil, France. 6. Hôpitaux Universitaires de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France. 7. Pôle Psychiatrie Universitaire, CHU Sainte-Marguerite, 13274, Marseille cedex 09, France. 8. Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Institut Pierre Louis d'Epidémiologie et de Santé Publique, 75013, Paris, France. 9. INSERM U955, Translational Psychiatry Team, DHU Pe-PSY, Centre Expert Schizophrénie, Pôle de Psychiatrie et d'Addictologie des Hôpitaux Universitaires Henri Mondor,, Paris Est University, 40 rue de Mesly, 94000, Créteil, France. 10. Centre Hospitalier Charles Perrens, Université de Bordeaux, 33076, Bordeaux, France. 11. Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, 33000, Bordeaux, France. 12. Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France. 13. CMP B, CHU, EA 7280 Faculté de Médecine, Université d'Auvergne, BP 69 63003, Clermont-Ferrand Cedex 1, France. 14. AP-HP, Department of Psychiatry, Inserm U894, Sorbonne Paris Cité, Faculté de médecine, Louis Mourier Hospital, Université Paris Diderot, Colombes, France. 15. Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France. 16. Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France. 17. CNRS UMR 5287-INCIA, Bordeaux, France. 18. Université Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier Pole Est, 95 bd Pinel, BP 300 39, 69678, BRON Cedex, France. 19. Service de Psychiatrie d'Adulte, Centre Hospitalier de Versailles, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France.
Abstract
OBJECTIVE: The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. METHOD: 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). RESULTS: In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. CONCLUSION: BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine intake and testing, as well as the specific class of benzodiazepines (long half-life vs. short half-life), and the number of benzodiazepine daily intakes have not been recorded in the present study. The precise motive for BLTA prescription and sleep disturbances have not been reported, which is a limit for the interpretation of the present results.
OBJECTIVE: The effect of benzodiazepine long-term administration (BLTA) in cognitive functioning of subjects with schizophrenia (SZ) has been partially explored to date. The objective was to assess BLTA-associated cognitive impairment with a comprehensive cognitive battery in a non-selected multicentric/national community-dwelling sample of stabilized SZ subjects. METHOD: 407 community-dwelling stabilized SZ subjects were consecutively included in the FondaMental Academic Centers of Expertise for Schizophrenia Cohort (FACE-SZ). Patients taking daily benzodiazepine were defined as BLTA+ as all patients examined by the Expert Center were clinically stabilized and under stable dose of treatment for at least 3 months. Each patient has been administered a 1-day long comprehensive cognitive battery (including The National Adult Reading Test, the Wechsler Adult Intelligence Scale, the Trail Making Test, the California Verbal Learning Test, the Doors test, and The Continuous Performance Test-Identical Pairs). RESULTS: In the multivariate analyses, results showed that BLTA was associated with impaired attention/working memory (OR 0.60, 95% confidence interval 0.42-0.86; p = 0.005) independently of socio-demographic variables and illness characteristics. Verbal and performance current IQ-[respectively, OR 0.98, 95% CI (0.96;0.99), p = 0.016 and 0.98, 95% CI(0.97;0.99), p = 0.034] but not premorbid IQ-(p > 0.05) have been associated with BLTA in a multivariate model including the same confounding variables. CONCLUSION: BLTA is associated with impaired attention/working memory in schizophrenia. The BLTA benefit/risk ratio should be regularly reevaluated. Alternative pharmacological and non-pharmacological strategies for comorbid anxiety disorders and sleep disorders should be preferred when possible. It seems reasonable to withdraw BLTA before the start of cognitive remediation therapy, as soon as possible, to improve the effectiveness of this therapy. Limits: the delay between the last benzodiazepine intake and testing, as well as the specific class of benzodiazepines (long half-life vs. short half-life), and the number of benzodiazepine daily intakes have not been recorded in the present study. The precise motive for BLTA prescription and sleep disturbances have not been reported, which is a limit for the interpretation of the present results.
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