Suvorexant (an orexin blocker) for suicide risk in veterans with major depressive disorder

Orexin Antagonism to Target Mechanisms of Suicide Risk: A Proof-of-Concept Clinical Trial

Phase 2 Interventional Bronx Veterans Medical Research Foundation, Inc · NCT06854224

This trial will try daily suvorexant for four weeks to see if it is safe and tolerable for veterans with major depressive disorder who have had suicidal thoughts or attempts.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment30 (estimated)
Ages18 Years to 70 Years
SexAll
SponsorBronx Veterans Medical Research Foundation, Inc Academic / other
Locations1 site (The Bronx, New York)
Trial IDNCT06854224 on ClinicalTrials.gov

What this trial studies

This is a Phase 2, proof-of-concept interventional trial testing the orexin antagonist suvorexant in veteran adults with major depressive disorder and elevated suicide risk. Participants take 10 mg nightly for the first two weeks and 20 mg nightly for the second two weeks, with in-person visits at baseline, week 3, and week 5 and remote self-report assessments at weeks 2 and 4. The primary focus is on initial safety, feasibility, and tolerability of daily suvorexant in this population. The trial excludes people with certain medical, substance use, or psychiatric conditions that could confound safety or interpretation.

Who should consider this trial

Good fit: Ideal candidates are veteran adults aged 18–70 with a primary diagnosis of major depressive disorder and a history of suicide attempt plus current suicidal ideation (C-SSRS score ≥2) who are medically stable and not taking contraindicated medications.

Not a fit: Patients with active substance use disorder, bipolar or psychotic disorders, severe medical or neurological conditions, pregnancy or breastfeeding, or who need contraindicated medications are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, this could identify a potentially safe short-term medication approach that might help address sleep-related drivers of suicidal thoughts in veterans with depression.

How similar studies have performed: Orexin antagonists like suvorexant are approved for insomnia and have an established safety profile for sleep, but using them specifically to reduce suicide risk is largely novel and has limited prior evidence.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* Veteran
* At least 18 years of age (up to 70 years)
* Primary diagnosis of Major Depressive Disorder as determined by the study psychiatrist and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
* Lifetime suicide attempt history and suicidal ideation at baseline as determined by a score ≥2 on the Columbia-Suicide Severity Rating Scale (C-SSRS)

Exclusion Criteria:

* Clinically significant medical or neurological condition
* Current use of strong CYP3A live enzymes or moderate CYP3A inhibitors or strong CYP3A inducers
* Current use of digoxin
* Currently pregnant, not using contraception, nursing, or trying to become pregnant
* Active substance use disorder in the last six months, disorder, or current or past psychotic disorder, bipolar disorder, or obsessive-compulsive disorder
* Severe traumatic brain injury
* Imminent suicidal or homicidal risk
* Free of unstable medical conditions or any contraindication to suvorexant (per FDA prescribing label) as determined by patient interview and review of available medical records.

Where this trial is running

The Bronx, New York

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Suicide RiskMajor Depressive DisorderSuicide riskProof-of-concept clinical trialSuvorexantOrexin antagonist
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.