Association Between Non-Benzodiazepine Hypnotics and Tinnitus: A Nationwide Cohort Study in Taiwan

Non-benzodiazepine hypnotics, commonly known as Z-drugs, are widely prescribed for conditions such as insomnia, anxiety, and epilepsy. Emerging evidence suggests that these agents may influence auditory function and may be associated with tinnitus, potentially through their modulation of GABAA receptors. However, existing research findings on this association remain inconsistent. The objective of this study was to examine the potential association between the use of Z-drugs and the subsequent risk of incident tinnitus.

This study was conducted using the Taiwan Longitudinal Health Insurance Database. The exposure cohort was composed of all beneficiaries who were prescribed a Z-drug during the study period. The comparison cohort was selected from beneficiaries without any prescription history for Z-drugs during the same timeframe. The primary outcome was the risk of tinnitus within a 5-year follow-up period. To minimize potential confounding, propensity score matching was applied, followed by Cox proportional hazards regression analyses to calculate hazard ratios (HRs) comparing Z-drug users with nonusers.

16,225 patients were identified as Z-drug users, while 1,370,776 were classified as nonusers. Over the 5-year period, Cox proportional hazards regression analysis revealed that Z-drug users had a higher risk of developing tinnitus compared to nonusers (adjusted HR: 1.501; 95% CI: 1.423-1.583). After propensity score matching, this association remained significant (adjusted HR: 1.496; 95% CI: 1.377-1.624). Furthermore, a consistent association between Z-drug use and tinnitus was observed across most subgroups.

The study suggests that the use of Z-drugs, the most prescribed psychoactive drugs globally, may be associated with an increased risk of developing tinnitus. Limitations include the potential for residual confounding and misclassification inherent to claims-based data. Clinicians should consider this potential association when prescribing Z-drugs.