spec sheet11 rows
Filorexant merck's second dual orexin antagonist (MK-6096); a shorter-acting DORA studied for insomnia and then, unsuccessfully, for depression, before development was discontinued.
- explored the orexin class for both insomnia and depression
- its negative depression result helped redirect the field toward selective OX2 antagonism
- somnolence
- suicidal ideation reported in the depression trial
- orexin-class cautions (next-day sedation; theoretical sleep paralysis/hallucinations)
Overview
the 'other' merck orexin drug. filorexant looked reasonable for sleep and was pushed into a proof-of-concept depression trial that came up empty (partly because the study couldn't enroll enough patients); merck ultimately did not advance it, focusing on suvorexant instead.
- filorexant's depression trial is one of the key negative data points arguing that broad dual orexin block is not an antidepressant, which helped shift interest toward selective OX2 antagonism (seltorexant).
- the depression study had to stop early because it could not enroll enough patients, so it was underpowered even before the negative result.
- merck ran filorexant and suvorexant in parallel and ultimately backed suvorexant to market.
Mechanism
filorexant is a dual receptor that blocks OX1R and OX2R with balanced, potent activity, reducing orexin wake-drive to promote sleep; it has a shorter duration of action than suvorexant. beyond insomnia, merck tested the orexin-block-as-antidepressant hypothesis (orexin signaling is tied to stress, arousal, and reward), adding filorexant to ongoing antidepressants in partial responders. the biological rationale was plausible but the clinical result was negative.
receptor fingerprint
OX1R (-1 / HCRTR1)competitive antagonist
OX2R (-2 / HCRTR2)competitive antagonist
Dosingtypical ranges, not medical advice
interested in protocols and clinical dosages? make an account to see them! ^_^
Safetyrisks and cautions, not medical advice
investigational-only; never approved. in the depression trial the most common adverse events were somnolence and suicidal ideation, and the study was underpowered because it terminated early for enrollment reasons (connor 2017). standard orexin-class cautions (next-day sedation, and theoretical sleep paralysis/hallucinations/cataplexy-like effects) apply. not available as a medicine.
History
developed by merck as MK-6096 alongside suvorexant. it advanced into phase 2 for insomnia and into a phase 2 proof-of-concept trial as add-on therapy for major depressive disorder (NCT01554176), which was negative and terminated early for poor enrollment (connor 2017). merck did not carry it forward as a marketed product.
Reputation
a footnote DORA; useful mainly as evidence in the 'can orexin blockers treat depression?' debate, where a dual antagonist (filorexant) failed while the selective OX2 antagonist seltorexant later showed signals in insomnia-heavy depression. otherwise it has no clinical standing.
Subjective profileweighing the evidence above
A footnote rather than an option. Development stopped, the depression trial reported somnolence and suicidal ideation in an underpowered study, and its real legacy is having pushed the orexin field toward selective OX2 blockade instead.
Resources
This entry is here for reference.
Research
- 1.Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder.
- 2.Orexin Receptor Antagonists in the Treatment of Depression: A Leading Article Summarising Pre-clinical and Clinical Studies.
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
is filorexant available?
no; it was never approved and development did not advance to a marketed product. it is investigational only.
did filorexant treat depression?
no. in a phase 2 add-on trial in major depression it did not separate from placebo, and the study was underpowered because it stopped early for enrollment problems (connor 2017). that negative signal is its main scientific legacy.
how is it different from suvorexant?
both are merck dual orexin antagonists; filorexant is shorter-acting and was never marketed, while suvorexant became belsomra. merck ultimately backed suvorexant.
why do orexin drugs get tested for depression at all?
orexin neurons sit at the crossroads of arousal, stress, and reward, all disturbed in depression, and many depressed patients have insomnia. the hypothesis was reasonable, but dual block (filorexant) failed; a selective OX2 blocker (seltorexant) later did better in insomnia-heavy depression.
Adverse effects
- somnolence
- suicidal ideation reported in the depression trial
- orexin-class cautions (next-day sedation; theoretical sleep paralysis/hallucinations)