Predictors, Incidence of Long-term Use of Benzodiazepines, Z-Drugs in Bipolar Disorder

Investigators sought to determine the incidence of benzodiazepine and Z-drug initiation and predictors of long-term use in patients with bipolar disorder.

Individuals with bipolar disorder who start benzodiazepines and/or Z-drugs, particularly alprazolam and clonazepam, have an increased risk for long-term use, resulting in an increased risk for adverse effects associated with these medications, according to an analysis published in Bipolar Disorders.

Data from adult patients with bipolar disorder or mania who had no history of benzodiazepine or Z-drug (sleep-inducing hypnotics) use in the past year were obtained from Swedish national registers. Patients who initiated therapy were followed for 1 year to determine the proportion who experienced long-term use of >6 months. The investigators evaluated both patient and prescription characteristics to determine potential predictors of long-term drug use.

In this study, a total of 21,883 adult patients with bipolar disorder/mania were included in the final analysis. Of these patients, 6307 (28.8%) initiated therapy with benzodiazepine/Z-drugs. Approximately 1 in 5 patients who initiated therapy during the study period became long-term users, with alprazolam and clonazepam being the strongest predictors for long-term use (adjusted odds ratio [aOR] 2.03; 95% CI, 1.30-3.18 and aOR 3.78; 95% CI, 2.24-6.38, respectively).

Patients prescribed ≥2 benzodiazepines and/or Z-drugs also had a higher odds of becoming long-term users (aOR 2.46; 95% CI, 1.79-3.38). In addition, patients age ≥60 years had a higher likelihood of long-term drug use when compared with patients <30 years old (aOR 1.93; 95% CI, 1.46-2.53, compared with age <30 years), and concomitant psychostimulant (aOR 1.78, 95% CI, 1.33-2.39), lamotrigine (aOR 1.21; 95% CI, 1.04-1.42), and non-mood-stabilizing antipsychotic (aOR 1.53, 95% CI, 1.29-1.82) medication use was associated with a higher risk for long-term use of benzodiazepines/Z-drugs.

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Despite the risks associated with long-term benzodiazepines/Z-drug use, it is possible that the proportion of patients in this study who used these drugs long term may likely benefit from longer treatment durations. The inability to determine whether long-term users were dependent or abused these drugs, primarily because of the lack of data on benzodiazepines/Z-drug dosages, further limits the findings.

The investigators emphasize that alprazolam and clonazepam “should be used very restrictively when treating anxiety or insomnia in bipolar disorder and that prescriptions of more than one benzodiazepine or Z-drug should be avoided to reduce long-term benzodiazepine use in this vulnerable population.”


Wingård L, Taipale H, Reutfors J, et al. Initiation and long-term use of benzodiazepines and Z-drugs in bipolar disorder [published online February 16, 2018]. Bipolar Disord. doi:10.1111/bdi.12626