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

Louise Wingård; Heidi Taipale; Johan Reutfors; Anna Westerlund; Robert Bodén; Jari Tiihonen; Antti Tanskanen; Morten Andersen

doi:10.1111/bdi.12626

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

Louise Wingård^*, Heidi Taipale, Johan Reutfors, Anna Westerlund, Robert Bodén, Jari Tiihonen, Antti Tanskanen, Morten Andersen

^*Corresponding author for this work

9 Citations (Scopus)

Abstract

Objectives: Increasing 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. Methods: 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 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as “long-term”. Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. Results: Out of the 21 883 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 ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). Conclusions: 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.

Original language	English
Journal	Bipolar Disorders
Volume	20
Issue number	7
Pages (from-to)	634-646
Number of pages	13
ISSN	1398-5647
DOIs	https://doi.org/10.1111/bdi.12626
Publication status	Published - 2018

Keywords

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

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10.1111/bdi.12626

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@article{3aef6a9ef7cb4c489b1dfda33f2713c1,

title = "Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder",

abstract = "Objectives: Increasing 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. Methods: 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 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as “long-term”. Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. Results: Out of the 21 883 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 ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). Conclusions: 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.",

keywords = "benzodiazepines, bipolar disorder, cohort study, drug utilization study, prescription drug misuse, zaleplon, zolpidem, zopiclone",

author = "Louise Wing{\aa}rd and Heidi Taipale and Johan Reutfors and Anna Westerlund and Robert Bod{\'e}n and Jari Tiihonen and Antti Tanskanen and Morten Andersen",

year = "2018",

doi = "10.1111/bdi.12626",

language = "English",

volume = "20",

pages = "634--646",

journal = "Bipolar Disorders, Supplement",

issn = "1399-2406",

publisher = "Wiley-Blackwell",

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TY - JOUR

T1 - Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder

AU - Wingård, Louise

AU - Taipale, Heidi

AU - Reutfors, Johan

AU - Westerlund, Anna

AU - Bodén, Robert

AU - Tiihonen, Jari

AU - Tanskanen, Antti

AU - Andersen, Morten

PY - 2018

Y1 - 2018

N2 - Objectives: Increasing 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. Methods: 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 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as “long-term”. Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. Results: Out of the 21 883 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 ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). Conclusions: 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.

AB - Objectives: Increasing 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. Methods: 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 1 year with regard to prescription fills of benzodiazepines/Z-drugs. Initiators were followed for another year during which continuous use for >6 months was defined as “long-term”. Patient and prescription characteristics were investigated as potential predictors for long-term use in multivariate logistic regression models. Results: Out of the 21 883 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 ≥60 years (aOR 1.93, 95% CI 1.46-2.53, compared to age <30 years), and concomitant treatment with psychostimulants (aOR 1.78, 95% CI 1.33-2.39). Conclusions: 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.

KW - benzodiazepines

KW - bipolar disorder

KW - cohort study

KW - drug utilization study

KW - prescription drug misuse

KW - zaleplon

KW - zolpidem

KW - zopiclone

U2 - 10.1111/bdi.12626

DO - 10.1111/bdi.12626

M3 - Journal article

C2 - 29450954

AN - SCOPUS:85049861679

SN - 1399-2406

VL - 20

SP - 634

EP - 646

JO - Bipolar Disorders, Supplement

JF - Bipolar Disorders, Supplement

IS - 7

ER -

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

Abstract

Keywords

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