DOI: 10.1111/acps.70121 ISSN: 0001-690X

Benzodiazepine Use and Mortality Risk: A Nationwide Cohort Study on New Benzodiazepine Users With a 5‐Year Follow‐Up

Hanna Särkilä, Heidi Taipale, Antti Tanskanen, Tero Taiminen, Reijo Sund, Terhi Kurko, Jarmo Hietala, Solja Niemelä
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ABSTRACT

Introduction

We aimed to investigate the risks of all‐cause and cause‐specific mortality associated with dose‐dependent benzodiazepine and Z‐drug ( BZDR) use in the Finnish population initiating new BZDR use with five‐year follow‐up.

Methods

Study subjects were included if BZDR use had started in 2006 with no BZDR dispensing during the preceding years 2004–2005. The information drug dispensing was modeled with PRE2DUP method as time‐varying measure updated at every dispensing and then divided into three dose categories which were low dose (< 1.0 Defined Daily Doses [DDDs] per day), medium to high dose (1.0–< 3.0 DDDs/day) and very high‐dose (≥ 3.0 DDDs/day). Risk of mortality was studied with Cox regression models.

Results

The study included 48,124 incident BZDR users aged 18–65 years (44.4% male). During the 5‐year follow‐up, 2294 (4.9%) individuals died. Compared to non‐use periods, BZDRs use was associated with increased mortality risk (adjusted Hazard Ratio HR 1.28, 95% Confidence Interval CI 1.16–1.41). Compared to the time periods when BZDRs were not used, both medium to high‐dose use ( aHR 1.58, 1.36–1.74) and very‐high‐dose use ( aHR 2.68, 95% CI 2.20–3.26) were associated with an increased risk of all‐cause mortality, whereas low dose use was not. The highest risk estimates were observed during very high‐dose use and for potentially preventable deaths such as overdoses ( aHR 6.18, 95% CI 3.77–10.12), suicides ( aHR 4.46, 95% CI 2.79–7.13), and accidents ( aHR 3.77, 95% CI 2.66–5.35).

Conclusions

Persons using BZDRs in very high doses are at a six‐fold increased risk of overdose deaths compared to non‐use, and those using BZDRs in medium to high doses are at a three‐fold increased risk. In low doses, however, the risk of all‐cause mortality was not elevated. The mortality risk strongly associates with higher doses and is often characterized by concomitant use of more than one BZDRs at the same time.

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