Orexin receptor antagonism may offer a novel treatment approach to insomnia, clinical findings suggest.
"Antagonism of orexin peptide receptors selectively dampens unwanted wakefulness interfering with sleep," the researchers explain in Neurology.
This provides an alternative treatment pathway to existing benzodiazepine receptor agonist treatments, which act on the widely distributed γ-aminobutyric acid A receptor system, they add.
The team, led by W Joseph Herring (Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, USA), studied the effects of the orexin receptor antagonist suvorexant in treating 254 people aged 18 to 64 years with moderately severe insomnia.
The participants were randomly assigned to take either suvorexant, at doses of 10, 20, 40, or 80 mg, or placebo for 4 weeks, after which they switched to the alternative treatment for a further 4 weeks.
Their sleep was monitored in a sleep laboratory on the first night of taking each treatment and again in the fourth week of each treatment.
Sleep efficiency, reflecting the time patients spent in bed at night asleep, was an average 66% (with an average total sleep time of 316 minutes) before treatment and improved by a significant 5.2% to 12.9% on the first night of treatment with suvorexant, compared with placebo.
Suvorexant treatment also resulted in patients experiencing 21 to 37 fewer minutes awake during the first night when compared with placebo.
The benefits of suvorexant were maintained over the 4 weeks of the study, with a significant 4.7% to 10.4% improvement in sleep efficiency, compared with placebo.
For both outcomes, the effect was dose-related and all doses were superior to placebo for improving sleep efficiency on night 1 and at the end of week 4.
Dose-related effects were also seen for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset).
The researchers note that, overall, suvorexant was well tolerated. The most common adverse event associated with the drug was somnolence, which showed a dose-related increase.
But there was no consistent evidence of rebound insomnia or withdrawal effects after 4 weeks of treatment, or for next-day residual effects.
"This study provides evidence that suvorexant may offer a successful alternative strategy for treating insomnia," Herring said in a press statement.
The team now calls for further study to "more fully characterize the clinical profile of suvorexant," including trials involving a greater number of patients, longer treatment duration, and elderly patients, who comprise a large proportion of those with insomnia.
Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.