Long-term use of zolpidem increases the risk of major injury: a population-based cohort study

To estimate the risk of head injury or fracture requiring hospitalization in patients treated with zolpidem.

We identified 8188 patients 18 years and older who had received a first prescription for zolpidem between January 1, 2000, and December 31, 2009, and compared them with 32,752 age- and sex-matched patients who had not used sedative-hypnotic agents. Both cohorts were followed up for at least 1 year or until hospitalization for head injury or fracture (major injury). Hazard ratios (HRs) and 95% CIs were calculated by comparing the incidence of major injury requiring hospitalization between the zolpidem user and comparison cohorts, including age groups 18 to 54 and 55 years or more, using a Cox proportional hazards regression analysis.

The adjusted HR for major injury in zolpidem users was 1.67 (95% CI, 1.19-2.34). The adjusted HR for major injury in zolpidem users in the younger cohort (aged 18-54 years) was 1.70 (95% CI, 1.15-2.51) and in the older cohort (aged ≥55 years) was 1.57 (95% CI, 0.78-3.13). The adjusted HR for major injury in zolpidem users increased when the zolpidem dosage increased (HR, 2.04; 95% CI, 1.32-3.13 for 71-800 mg/y; HR, 4.37; 95% CI, 2.12-9.01 for 801-1600 mg/y; and HR, 4.74; 95% CI, 2.38-9.42 for >1600 mg/y).

The long-term use of zolpidem is associated with a significantly greater risk of head injury or fracture requiring hospitalization than in patients who do not use sedative-hypnotic agents (P<.001), particularly in the younger (aged 18-54 years) patients.