Zolpidem Increased Cancer Risk in Patients with Sleep Disorder: A 3‑year Follow‑up Study

Background: Zolpidem has been increasingly used in patients with sleep disorder due to its minimal respiratory depressor effects and short half-life. Materials and Methods: Recent case reports indicate that zolpidem usage may be associated with increased cancer mortality. This study aimed to determine the impact of zolpidem usage on the risk of incident cancer events in sleep disorder patients over a 3-year follow-up. Of the 6924 subjects diagnosed with sleep disorder in 2004, 1728 had used zolpidem. A Cox proportional hazard model was performed to estimate 3-year cancer event-free survival rates for patients using zolpidem and those not using it, after adjusting for confounding and risk factors. Results: At the end of follow-up, 56 patients had incident cancers, 26 (1.5%) who used zolpidem, and 30 (0.6%) who did not. After adjustments for gender, age, comorbidities, and other medications, patients using zolpidem had a 1.75 times (95% confidence interval [CI], 1.02-3) greater risk of cancer events than those not using zolpidem during the 3-year follow-up. Greater mean daily dose and longer use were associated with increased risk. Among patients with sleep disorder, mean daily dose ＞10 mg and length of drug use ＞2 months was associated with 3.74 times greater risk (95% CI, 1.42-9.83; P = 0.008) of incident cancer events. Conclusions: In this study, zolpidem use increased cancer events risk in sleep disorder patients. Risks and benefits of chronic zolpidem usage should be explained to sleep disorder patients, and long-term use should be monitored.