Is seltorexant, an orexin-2 receptor antagonist, showing promise in insomnia?

Insomnia is common. Seltorexant (JNJ-42847922), a selective orexin-2 receptor antagonist, was originally trialed in major depression. In a repurposing, seltorexant has been tested in a phase 2b trial for insomnia. This trial represents a new approach to treat insomnia. The primary efficacy endpoint was latency to persistent sleep (LPS) on night 1, which was shortened with seltorexant. In addition to shortening the time to go to sleep in subjects with insomnia, Seltorexant prolonged sleeping time before waking. Comparison showed more benefit and less adverse effects with seltorexant than with zolpidem, an established treatment for insomnia. The findings that (i) the effects of seltorexant may diminish with time, depending on dose and (ii) that the overall incidence of treatment-emergent adverse effects was lower with seltorexant than with placebo, need explanation. A phase 3 trial of seltorexant in depression and insomnia is underway. As seltorexant is showing promise in insomnia, further trials are needed. However, at present, there are no phase 3 clinical trials registered for the treatment of insomnia by seltorexant alone or in comparison with zolpidem, and such trials need consideration.