Long-term effects of introducing novel hypnotics to users of benzodiazepine receptor agonist hypnotics

Long-term use of benzodiazepine receptor agonists (BZRAs) for insomnia causes several adverse events, such as dependency and cognitive impairment. Novel hypnotics are safer, but switching from BZRAs is difficult. We aimed to clarify how initiating novel hypnotics impacts BZRA reduction, focusing on prior BZRA use duration.

A retrospective cohort study at two hospitals in Japan evaluated outpatients on BZRAs who initiated novel hypnotics from May 1, 2021, to April 30, 2022. The primary outcome was the success rate of BZRA hypnotic reduction (by at least one agent) at the 1-year follow-up. The duration of BZRA use and successful reduction were assessed using multivariate logistic regression.

In total, 3802 patients were prescribed 5114 hypnotics (novel hypnotics, 38%); 190 patients met the criteria for novel hypnotic initiation while receiving BZRA hypnotics. At the end of the follow-up period, 46% of the patients achieved BZRA hypnotic reduction. The success rate for BZRA hypnotic reduction was significantly higher in patients with <1 vs. ≥1 year of prior BZRA use (69% vs. 36%, p < 0.0001). After adjusting for covariates, the odds ratios for successful reduction were 0.21 (95% CI: 0.08-0.56) vs. 0.16 (95% CI: 0.06-0.43) for 1-5 vs. ≥5 years of use, relative to non-regular use.

Initiating novel hypnotics may be effective in BZRA hypnotic reduction, while success rates decline sharply with the duration of prior BZRA use. To preserve the feasibility of medication withdrawal, avoiding long-term BZRA therapy and prioritizing the use of safer novel hypnotics may be a good approach.