4.4 Article

Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder

Journal

BIPOLAR DISORDERS
Volume 20, Issue 7, Pages 634-646

Publisher

WILEY
DOI: 10.1111/bdi.12626

Keywords

benzodiazepines; bipolar disorder; cohort study; drug utilization study; prescription drug misuse; zaleplon; zolpidem; zopiclone

Funding

  1. Novo Nordisk Foundation [NNF15SA0018404]
  2. Swedish Research Council [2016-02362]
  3. Karolinska Institutet Funds [2013-37903]
  4. Fredrik O Ingrid Thurings Foundation [2015-00114]
  5. Capio Research Foundation [2014-2722]
  6. Bror Gadelius Memorial Fund
  7. Soderstrom-Konig Foundation [SLS-480131]
  8. Swedish Society of Medicine [SLS-502541, SLS-587661]

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ObjectivesMethodsIncreasing evidence points to the harmful effects of long-term benzodiazepine treatment. Our objective was to study the incidence of, and predictors for, long-term use of benzodiazepines and Z-drugs in bipolar disorder. We conducted a population-based cohort study, using data from Swedish national registers. Swedish residents aged 18-75 years with a recorded diagnosis of bipolar disorder or mania between July 2006 and December 2012, and no history of benzodiazepine/Z-drug use in the past year, were included. Patients were followed for 1year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6months was defined as long-term. Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. ResultsConclusionsOut of the 21883 patients included, 29% started benzodiazepine/Z-drug treatment, of whom one in five became long-term users. Patients who were prescribed clonazepam or alprazolam had high odds for subsequent long-term use (adjusted odds ratios [aORs] 3.78 [95% confidence interval (CI) 2.24-6.38] and 2.03 [95% CI 1.30-3.18], respectively), compared to those prescribed diazepam. Polytherapy with benzodiazepines/Z-drugs also predicted long-term use (aOR 2.46, 95% CI 1.79-3.38), as did age 60years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). The incidence of subsequent long-term use among bipolar benzodiazepine initiators is high. Patients on clonazepam, alprazolam or benzodiazepine/Z-drug polytherapy have the highest risk of becoming long-term users, suggesting that these treatments should be used restrictively.

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