Incidence of and Characteristics Associated With Long-term Benzodiazepine Use in Finland

Heidi Taipale,Jari Tiihonen,Terhi Kurko,Leena Saastamoinen,Antti Tanskanen,Annamari Tuulio-Henriksson,Jarmo Hietala,Hanna Särkilä,Tero Taiminen,Reijo Sund

doi:10.1001/jamanetworkopen.2020.19029

Abstract

The proportion of patients who develop long-term benzodiazepine use remains controversial, as do the length of time before long-term use develops and the factors associated with long-term use. To investigate the incidence of long-term benzodiazepine and related drug (BZDR) use and factors associated with the development of long-term use implementing a follow-up design with new BZDR users. This population-based cohort study used a nationwide cohort of 129 732 new BZDR users in Finland. New users of BZDRs aged 18 years or older were identified from the prescription register maintained by the Social Insurance Institution of Finland as individuals who initiated BZDR use during 2006 and had not used BZDRs from 2004 to 2005. The follow-up continued until death, long-term hospitalization, a gap of 2 years in BZDR use, or December 31, 2015. The population was analyzed according to age at treatment initiation, categorized into younger (<65 years) and older (≥65 years) subcohorts. Analyses were conducted from May 2019 to February 2020. Use of BZDRs, modeled from register-based data using the PRE2DUP (from prescriptions to drug use periods) method. Long-term BZDR use, defined as continuous use of 180 days or longer, and factors associated with long-term vs short-term use, compared using Cox proportional hazards models. Among the 129 732 incident BZDR users, the mean (SD) age was 52.6 (17.7) years, and 78 017 (60.1%) individuals were women. During the follow-up period, 51 099 BZDR users (39.4%) became long-term users. Long-term treatment was more common in the older subcohort (19 103 individuals [54.5%]) than the younger subcohort (31 996 individuals [33.8%]). At 6 months, 28 586 individuals (22.0%) had become long-term users: 11 805 (33.7%) in the older subcohort and 16 781 (17.7%) in the younger subcohort. The largest proportions of initiators who became long-term users were those persons who initiated treatment with nitrazepam (76.4%; 95% CI, 73.6%-79.1%), temazepam (63.9%; 95% CI, 62.9%-65.0%), lorazepam (62.4%; 95% CI, 59.7%-65.1%), or clonazepam (57.5%; 95% CI, 55.9%-59.2%). Factors associated with the development of long-term use included male sex, older age, receipt of social benefits, psychiatric comorbidities, and substance abuse. The findings of this population-based cohort study conducted in Finland suggest that the incidence of subsequent long-term BZDR use in individuals who initiate use of BZDRs is high, especially among older persons, and that the specific BZDR used initially is associated with the development of long-term BZDR use and should be carefully considered when prescribing BZDRs. The observed factors that appear to be associated with development of long-term BZDR use also should be considered in clinical decision-making when starting and monitoring BZDR treatment.

Highlights

Factors associated with the development of long-term use included male sex, older age, receipt of social benefits, psychiatric comorbidities, and substance abuse. The findings of this population-based cohort study conducted in Finland suggest that the incidence of subsequent long-term benzodiazepine and related drug (BZDR) use in individuals who initiate use
Most Common BZDRs Initiated In both subcohorts, zopiclone was the most common BZDR at the initiation of use; 30 176 (31.9%) of the younger users and 13 875 (39.6%) of the older users initiated treatment with zopiclone
The results of this study suggest that new BZDR users frequently become long-term users; one-third of persons younger than 65 years and about 55% of persons aged 65 years or older were defined as long-term users, and a substantial proportion developed long-term use quickly, without having any gaps in use after initiation

Summary

Introduction

The rationale for long-term use of benzodiazepines and related drugs (BZDRs) has long been a subject that has divided physicians all over the world.[1,2,3] The main concerns about benzodiazepine use are related to development of tolerance and dependence on regular use as well as adverse events, especially in older individuals.[4,5] several guidelines and recommendations for BZDR prescribing have been published over the years, emphasizing that duration of use should be limited to the short term (4-12 weeks).[6,7,8,9,10,11,12,13] Some authors suggest that BZDR benefits may persist, at least in specific patient groups,[14,15,16,17] and that the risk-benefit ratio of long-term use (eg, in anxiety disorders) has not been properly studied in comparison with alternative pharmacotherapeutic approaches such as the administration of selective serotonin reuptake inhibitors.[18,19]Despite all the recommendations, a vast amount of literature shows that long-term use is still very common, especially in older patients, and further research on the topic is needed to optimize the use of BZDRs.[20,21] Among older persons, BZDR use has been associated with cognitive and psychomotor adverse effects and an increased risk of falls,[22] fractures,[23,24] and even mortality.[25]. General factors associated with long-term BZDR use, according to previous studies, include sex, comorbid conditions, older age, lower income, and poorer health status.[20,26,27] Some studies point toward problems focused on specific substances, including alprazolam and clonazepam.[28,29,30] Concerns have been raised about the increasing use of benzodiazepine-related drugs, often called Z-drugs, zolpidem.[28,30,31]

Methods

Results

Discussion

Conclusion