TABLE 4.

Orexinergic agents with antidepressant properties in the pipeline.

Authors/Trial sponsor	Methodology	Results	Clinical trial phase, trial identifier (if available)
Recourt et al. (2019)	Seltorexant (MIN-202, JNJ-42847922, JNJ-922) vs diphenhydramine vs placebo, DBRCT, N = 47, MDD, 4 weeks	Core symptoms of depression were improved after 10 days with seltorexant vs placebo and its efficacy persisted up to day 28	Phase Ib, NCT02476058
Savitz et al. (2021)	Seltorexant + ongoing antidepressant, DBRCT, N = 287, MDD with insufficient response to 1–3 SSRI/SNRI, 6 weeks	MADRS scores improved more in the seltorexant (20 mg) vs placebo at weeks 3 and 6. If baseline ISI≥15 the efficacy of seltorexant 20 mg/day was higher vs placebo	Phase IIb, NCT03227224
National Library of Medicine (2021c)	Seltorexant + ongoing antidepressant, DBRCT, N = 52 (estimated), MDD with inadequate response to SSRI/psychotherapy	The outcomes will be related to tolerability, depression severity, clinical global impression, sleep quality, cognitive performance, and pharmacokinetic parameters	Phase I, NCT04951609

DBRCT, double-blind randomized controlled trial; ISI, Insomnia Severity Index; MADRS, Montgomery-Asberg Depression Rating Scale; MDD, major depressive disorder; NLM, National Library of Medicine; SNRI, Serotonin and norepinephrine reuptake inhibitor; SSRI, Selective serotonin reuptake inhibitor.