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Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set

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European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

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.

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Acknowledgements

Andrianarisoa Méjad,l, MD PhD, Aouizerate Brunoa,l, MD PhD, Berna Fabriceb,l, MD PhD, Blanc Olivierc,l, MSc, Brunel Lored,l, MSc, Bulzacka Ewad,l, MSc, Capdevielle Delphinee,l, MD PhD, Chéreau-Boudet Isabellec,l, MD, Chesnoy-Servanin Gabriellef,l, MSc, Danion Jean-Marieb,l, MD, D’Amato Thierryf,l, MD PhD, Deloge Arnaudg,l, MD PhD, Delorme Claireh,l, MSc, Denizot Hélènec,l, MD, Dorey Jean-Michelf,l, MD, Dubertret Carolinei,l, MD PhD, Dubreucq Julienh,l, MD, Faget Catherinej,l, MD, Fluttaz Cécileh,l, MSc, Fond Guillaumed,l, MD, Fonteneau Sandrinek,l, MSc, Gabayet Franckh,l, MSc, Giraud-Baro Elisabethh,l, MD, Hardy-Baylé Marie-Christinek,l, MD PhD, Lacelle Delphinec,l, MSc, Lançon Christophej,l, MD PhD, Laouamri Hakiml, MSc, Leboyer Mariond,l, MD PhD, Le Gloahec Tifennd,l, MSc, Le Strat Yanni,l, MD PhD, Llorca Pierre-Michelc,l, MD PhD, Mallet Jasminai,j, MD PhD, Metairie Emelinej,l, MSc, Misdrahi Davidg,l, MD, Offerlin-Meyer Isabelleb,l, PhD, Passerieux Christinek,l, MD PhD, Peri Paulinej,l, MSc, Pires Sylviec,l, MSc, Portalier Célinei,l, MSc, Rey Romainf,l, MD, Roman Célineh,l, MSc, Sebilleau Mathildek,l, MSc, Schandrin Auréliee,l, MD, Schurhoff Franckd,l, MD PhD, Tessier Arnaudg,l, MSc, Tronche Anne-Mariec,l, MD, Urbach Mathieuk,l, MD, Vaillant Florencej,l, MSc, Vehier Aurélief,l, MSc, Vidailhet Pierreb,l, MD PhD, Vilà Estelleg,l, MSc, Yazbek Hanane,l, PhD, Zinetti-Bertschy Annab,l, MSc. a Centre Hospitalier Charles Perrens, F-33076 Bordeaux, France; Université de Bordeaux, Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France; b Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France; c CMP B, CHU, EA 7280 Faculté de Médecine, Université d’Auvergne, BP 69 63003 Clermont-Ferrand Cedex 1, France; d AP-HP, DHU Pe-PSY, Pôle de Psychiatrie et d’addictologie des Hôpitaux Universitaires H Mondor,INSERM U955, Eq. 15 Psychiatrie Translationelle, Université Paris Est-Créteil, Créteil, France; e Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France; f Université Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier Pole Est BP 300 39–95 bd Pinel-69678 BRON Cedex, France; g Centre Hospitalier Charles Perrens, F-33076 Bordeaux, France; Université de Bordeaux, CNRS UMR 5287-INCIA, France; h Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France; i AP-HP, Department of Psychiatry, Louis Mourier Hospital, Colombes, Inserm U894 Université Paris Diderot, Sorbonne Paris Cité, Faculté de médecine, France; j Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France; k Service de psychiatrie d’adulte, Centre Hospitalier de Versailles, Le Chesnay, EA 4047 HANDIReSP, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint-Quentin en Yvelines, Versailles, France; l Fondation Fondamental.

Author information

Authors and Affiliations

  1. Fondation FondaMental, Créteil, France

    Guillaume Fond, F. Berna, L. Boyer, O. Godin, L. Brunel, M. Andrianarisoa, B. Aouizerate, D. Capdevielle, I. Chereau, J. M. Danion, C. Dubertret, J. Dubreucq, C. Faget, F. Gabayet, T. Le Gloahec, P. M. Llorca, J. Mallet, D. Misdrahi, R. Rey, R. Richieri, C. Passerieux, C. Portalier, P. Roux, A. Vehier, H. Yazbek, F. Schürhoff & E. Bulzacka

  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, L. Brunel, M. Andrianarisoa, T. Le Gloahec, F. Schürhoff & E. Bulzacka

  3. Pôle Psychiatrie Universitaire, CHU Sainte-Marguerite, 13274, Marseille cedex 09, France

    L. Boyer

  4. Centre Hospitalier Charles Perrens, Université de Bordeaux, 33076, Bordeaux, France

    B. Aouizerate & D. Misdrahi

  5. Hôpitaux Universitaires de Strasbourg, INSERM U1114, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France

    F. Berna & J. M. Danion

  6. Service Universitaire de Psychiatrie Adulte, Hôpital la Colombière, CHRU Montpellier, Université Montpellier 1, Inserm 1061, Montpellier, France

    D. Capdevielle & H. Yazbek

  7. CMP B, CHU, EA 7280 Faculté de Médecine, Université d’Auvergne, BP 69 63003, Clermont-Ferrand Cedex 1, France

    I. Chereau & P. M. Llorca

  8. Université Claude Bernard Lyon 1/Centre Hospitalier Le Vinatier Pole Est, 95 bd Pinel, BP 300 39, 69678, BRON Cedex, France

    R. Rey & A. Vehier

  9. AP-HP, Department of Psychiatry, Inserm U894, Sorbonne Paris Cité, Faculté de médecine, Louis Mourier Hospital, Université Paris Diderot, Colombes, France

    C. Dubertret, J. Mallet & C. Portalier

  10. Centre Référent de Réhabilitation Psychosociale, CH Alpes Isère, Grenoble, France

    J. Dubreucq & F. Gabayet

  11. Assistance Publique des Hôpitaux de Marseille (AP-HM), pôle universitaire de psychiatrie, Marseille, France

    C. Faget & R. Richieri

  12. 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

    C. Passerieux & P. Roux

  13. Inserm, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, U862, 33000, Bordeaux, France

    B. Aouizerate

  14. CNRS UMR 5287-INCIA, Bordeaux, France

    D. Misdrahi

  15. 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

    O. Godin

  16. Clinique Jeanne d’arc-Hôpital Privé Parisien, 55 rue du commandant Mouchotte, 94160, Saint-Mandé, France

    Guillaume Fond

  17. CHU Carémeau, 30000, Nîmes, France

    Guillaume Fond

Authors
  1. Guillaume Fond
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  2. F. Berna
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  3. L. Boyer
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  4. O. Godin
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  5. L. Brunel
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  6. M. Andrianarisoa
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  7. B. Aouizerate
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  8. D. Capdevielle
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  9. I. Chereau
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  10. J. M. Danion
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  11. C. Dubertret
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  12. J. Dubreucq
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  13. C. Faget
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  14. F. Gabayet
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  15. T. Le Gloahec
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  16. P. M. Llorca
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  17. J. Mallet
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  18. D. Misdrahi
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  19. R. Rey
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  20. R. Richieri
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  21. C. Passerieux
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  22. C. Portalier
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  23. P. Roux
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  24. A. Vehier
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  25. H. Yazbek
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  26. F. Schürhoff
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  27. E. Bulzacka
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Consortia

The FACE-SZ (FondaMental Academic Centers of Expertise for Schizophrenia) group

  • Méja Andrianarisoa
  • , Bruno Aouizerate
  • , Fabrice Berna
  • , Olivier Blanc
  • , Lore Brunel
  • , Ewa Bulzacka
  • , Delphine Capdevielle
  • , Isabelle Chéreau-Boudet
  • , Gabrielle Chesnoy-Servanin
  • , Jean-Marie Danion
  • , Thierry D’Amato
  • , Arnaud Deloge
  • , Claire Delorme
  • , Hélène Denizot
  • , Jean-Michel Dorey
  • , Caroline Dubertret
  • , Julien Dubreucq
  • , Catherine Faget
  • , Cécile Fluttaz
  • , Guillaume Fond
  • , Sandrine Fonteneau
  • , Franck Gabayet
  • , Elisabeth Giraud-Baro
  • , Marie-Christine Hardy-Baylé
  • , Delphine Lacelle
  • , Christophe Lançon
  • , Hakim Laouamri
  • , Marion Leboyer
  • , Tifenn Le Gloahec
  • , Yann Le Strat
  • , Pierre-Michel Llorca
  • , Jasmina Mallet
  • , Emeline Metairie
  • , David Misdrahi
  • , Isabelle Offerlin-Meyer
  • , Christine Passerieux
  • , Pauline Peri
  • , Sylvie Pires
  • , Céline Portalier
  • , Romain Rey
  • , Céline Roman
  • , Mathilde Sebilleau
  • , Aurélie Schandrin
  • , Franck Schurhoff
  • , Arnaud Tessier
  • , Anne-Marie Tronche
  • , Mathieu Urbach
  • , Florence Vaillant
  • , Aurélie Vehier
  • , Pierre Vidailhet
  • , Estelle Vilà
  • , Hanan Yazbek
  •  & Anna Zinetti-Bertschy

Corresponding author

Correspondence to Guillaume Fond.

Additional information

The members of the FACE-SCZ Group are listed in acknowledgements.

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Fond, G., Berna, F., Boyer, L. et al. Benzodiazepine long-term administration is associated with impaired attention/working memory in schizophrenia: results from the national multicentre FACE-SZ data set. Eur Arch Psychiatry Clin Neurosci 268, 17–26 (2018). https://doi.org/10.1007/s00406-017-0787-9

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  • DOI: https://doi.org/10.1007/s00406-017-0787-9

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