title: Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Fondation FondaMental, Créteil, France. guillaume.fond@gmail.com.|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.|Clinique Jeanne d'arc-Hôpital Privé Parisien, 55 rue du commandant Mouchotte, 94160, Saint-Mandé, France. guillaume.fond@gmail.com.|CHU Carémeau, 30000, Nîmes, France. guillaume.fond@gmail.com.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Fond
authors.affiliation: Fondation FondaMental, Créteil, France.|Hôpitaux Universitaires de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: F
authors.initials: F
authors.lastname: Berna
authors.affiliation: Fondation FondaMental, Créteil, France.|Pôle Psychiatrie Universitaire, CHU Sainte-Marguerite, 13274, Marseille cedex 09, France.
authors.forename: L
authors.initials: L
authors.lastname: Boyer
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: O
authors.initials: O
authors.lastname: Godin
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: L
authors.initials: L
authors.lastname: Brunel
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: M
authors.initials: M
authors.lastname: Andrianarisoa
authors.affiliation: Fondation FondaMental, Créteil, France.|Centre Hospitalier Charles Perrens, Université de Bordeaux, 33076, Bordeaux, France.|Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, 33000, Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Aouizerate
authors.affiliation: Fondation FondaMental, Créteil, France.|Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Capdevielle
authors.affiliation: Fondation FondaMental, Créteil, France.|CMP B, CHU, EA 7280 Faculté de Médecine, Université d'Auvergne, BP 69 63003, Clermont-Ferrand Cedex 1, France.
authors.forename: I
authors.initials: I
authors.lastname: Chereau
authors.affiliation: Fondation FondaMental, Créteil, France.|Hôpitaux Universitaires de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Danion
authors.affiliation: Fondation FondaMental, Créteil, France.|AP-HP, Department of Psychiatry, Inserm U894, Sorbonne Paris Cité, Faculté de médecine, Louis Mourier Hospital, Université Paris Diderot, Colombes, France.
authors.forename: C
authors.initials: C
authors.lastname: Dubertret
authors.affiliation: Fondation FondaMental, Créteil, France.|Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France.
authors.forename: J
authors.initials: J
authors.lastname: Dubreucq
authors.affiliation: Fondation FondaMental, Créteil, France.|Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Faget
authors.affiliation: Fondation FondaMental, Créteil, France.|Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France.
authors.forename: F
authors.initials: F
authors.lastname: Gabayet
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: T
authors.initials: T
authors.lastname: Le Gloahec
authors.affiliation: Fondation FondaMental, Créteil, France.|CMP B, CHU, EA 7280 Faculté de Médecine, Université d'Auvergne, BP 69 63003, Clermont-Ferrand Cedex 1, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Llorca
authors.affiliation: Fondation FondaMental, Créteil, France.|AP-HP, Department of Psychiatry, Inserm U894, Sorbonne Paris Cité, Faculté de médecine, Louis Mourier Hospital, Université Paris Diderot, Colombes, France.
authors.forename: J
authors.initials: J
authors.lastname: Mallet
authors.affiliation: Fondation FondaMental, Créteil, France.|Centre Hospitalier Charles Perrens, Université de Bordeaux, 33076, Bordeaux, France.|CNRS UMR 5287-INCIA, Bordeaux, France.
authors.forename: D
authors.initials: D
authors.lastname: Misdrahi
authors.affiliation: Fondation FondaMental, Créteil, France.|Université Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier Pole Est, 95 bd Pinel, BP 300 39, 69678, BRON Cedex, France.
authors.forename: R
authors.initials: R
authors.lastname: Rey
authors.affiliation: Fondation FondaMental, Créteil, France.|Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France.
authors.forename: R
authors.initials: R
authors.lastname: Richieri
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: C
authors.initials: C
authors.lastname: Passerieux
authors.affiliation: Fondation FondaMental, Créteil, France.|AP-HP, Department of Psychiatry, Inserm U894, Sorbonne Paris Cité, Faculté de médecine, Louis Mourier Hospital, Université Paris Diderot, Colombes, France.
authors.forename: C
authors.initials: C
authors.lastname: Portalier
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: P
authors.initials: P
authors.lastname: Roux
authors.affiliation: Fondation FondaMental, Créteil, France.|Université Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier Pole Est, 95 bd Pinel, BP 300 39, 69678, BRON Cedex, France.
authors.forename: A
authors.initials: A
authors.lastname: Vehier
authors.affiliation: Fondation FondaMental, Créteil, France.|Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France.
authors.forename: H
authors.initials: H
authors.lastname: Yazbek
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: F
authors.initials: F
authors.lastname: Schürhoff
authors.affiliation: Fondation FondaMental, Créteil, France.|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.
authors.forename: E
authors.initials: E
authors.lastname: Bulzacka
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced*; D001569:Benzodiazepines / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D008570:Memory, Short-Term / Q000187:drug effects*; D009483:Neuropsychological Tests; D025341:Principal Component Analysis; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines
keywords: Anxiety; Anxiolytics; Benzodiazepine; Cognition; Schizophrenia