Background
Although many pharmacologic therapies for insomnia are approved for short-term use, patients may use them chronically. Discontinuation of some hypnotic medications may lead to rebound insomnia or withdrawal. Lemborexant is an orally active, dual orexin receptor antagonist (DORA) approved for the treatment of insomnia in adults in several countries like Japan, Canada, the United States, and several Asian countries. Lemborexant has indicated substantial clinical benefit in the treatment of insomnia across phase II and III clinical trials
Methods
- A 12-month, global, multicenter, randomized, placebo-controlled, double-blind, parallel-group phase III study.
- Men and women aged >18 years with insomnia disease were required to have a history of subjective sleep-onset latency >30 min and a subjective wake-after-sleep onset >60 min at least three times weekly during the 4 weeks before enrollment.
- Subjects were randomized 1:1:1 to lemborexant 5 mg (LEM5) or 10 mg (LEM10) or placebo for 6 months.
- Thereafter, for extra 6 months, LEM5- and LEM10-treated subjects continued lemborexant, and the placebo group was rerandomized 1:1 to LEM5 or LEM10.
- Utilizing daily electronic sleep diaries patients reported sleep endpoints.
Results
- Sleep outcome improvements with lemborexant at month 12 were normally retained throughout the 2-week off-treatment period.
- <20% of subjects experienced a substantial worsening of insomnia symptoms.
- There was no evidence of withdrawal symptoms following lemobrexant discontinuation.
Conclusion
This analysis indicates rebound insomnia is improbable to occur with lemborexant and its effectiveness is maintained after abrupt discontinuation without placebo replacement following 6-12 months of treatment