Introduction Preclinical and clinical pharmacologic evidence indicate that orexin systems are relevant to sleep-wake cycle regulation and dimensions of reward and cognition, providing the basis to hypothesizing that they may be effective as therapeutics in mental disorders. Due to the limited efficacy and tolerability profiles of existing treatments for Major Depressive Disorder (MDD), investigational compounds in novel treatment classes are needed; seltorexant, an orexin receptor antagonist, is a potential new treatment currently under investigation.