Association of Zolpidem Use and Subsequent Increased Risk of Epilepsy: A Population-Based, Case-Control Study

Objective: To evaluate the impact of long-term zolpidem use on the subsequent risk of epilepsy.

Method: We used data from the National Health Insurance system of Taiwan to conduct a population-based case-control study. We identified 4,972 newly diagnosed epilepsy patients (ICD-9-CM code 345) for the period of 2005-2010 as cases. For each epilepsy case, 4 controls without a history of epilepsy were randomly selected from the rest of the population. Zolpidem was used as a predictor of epilepsy.

Results: Patients with epilepsy exhibited an adjusted odds ratio (OR) of 1.86 (95% CI, 1.70-2.03) and were, therefore, more strongly associated with zolpidem exposure than control patients were. The adjusted OR of epilepsy increased with the increase of mean zolpidem exposure (g/y). Compared with the OR of nonusers, the adjusted OR was 1.64 (95% CI, 1.44-1.86) for those who had taken < 1.0 g/y of zolpidem and 2.38 (95% CI, 2.06-2.74) for those who had taken ≥ 20.0 g/y of zolpidem. An adjusted OR of 3.55 (95% CI, 2.94-4.28) was noted to be associated with epilepsy when users had stopped taking the drug less than 7 days earlier. The estimated risk declined to an OR of 1.62 (95% CI, 1.47-1.78) when users had stopped taking the drug more than 90 days earlier.

Conclusions: This population-based, retrospective case-control study revealed a possible increase in epilepsy risk with zolpidem use, at either typical or supratherapeutic doses. These findings might stimulate public interest in safety issues regarding zolpidem use.