Effects of Dose Reduction or Discontinuation of Benzodiazepine Hypnotics on Sleep and Anxiety in Patients With Insomnia After Long-Term Use.

BACKGROUND

Long-term prescribing of benzodiazepine receptor agonists (BZRAs) is a problem worldwide, but there are no detailed reports on the effects or side effects of reducing or discontinuing the dose. We retrospectively investigated the efficacy and safety of discontinuing or reducing the dose of BZRAs hypnotics after long-term use.

METHODS

Between April 2018 and May 2019, patients with insomnia after long-term use of BZRA hypnotics had BZRA hypnotics discontinued or their dose reduced, and their sleep conditions and anxiety symptoms were assessed. Insomnia severity (primary endpoint) was assessed as the change from baseline after discontinuation or reduction of BZRA hypnotics using the Insomnia Severity Index Japanese version (ISI-J). Changes from baseline in sleep quality and anxiety symptoms (secondary endpoint) from baseline were assessed using the Pittsburgh Sleep Quality Index Japanese version (PSQI-J) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The adverse events were recorded during the study period. Statistical analysis was performed using the Wilcoxon matched-pairs signed rank test for changes in BZRA and concomitant medication dose, PSQI-J and GAD-7, and the paired t-test for changes in ISI-J.

RESULTS

The changes in ISI-J (discontinuation group: p = 0.07, reduction group: p = 0.91), PSQI-J (discontinuation group: p = 0.19, reduction group: p = 0.19), and GAD-7 scores (discontinuation group, p = 0.27; reduction group, p = 0.81) were not significant after the BZRA hypnotics were discontinued or reduced. Concomitant medications (antipsychotics and antidepressants) did not change from the baseline. The incidence of each adverse event did not change during the study period.

CONCLUSION

BZRA hypnotics can be discontinued or their dose reduced after long-term use without worsening sleep conditions and anxiety symptoms. Our results may provide a basis for the safe and effective discontinuation or dose reduction of long-term benzodiazepine hypnotics use.