Orexin Antagonism for Suicide Risk: A Proof-of-Concept Clinical Trial

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

The goal of this proof-of-concept clinical trial is to evaluate the initial safety, feasibility, and tolerability of the orexin mixed antagonist suvorexant in a sample of veteran adults with Major Depressive Disorder and elevated suicide risk. The main question it aims to answer is: Is Suvorexant safe, feasible, and tolerable for participants?

Participants will:

• Take Surovexant every day for four weeks (10mg in the first two weeks and 20mg in the second two weeks)
• Visit the medical center at the beginning of the study (week 1), after taking Suvorexant for two weeks (week 3) and following the full Suvorexant dose (week 5) for in-person assessments.
• Fill out self-report assessments (remotely) at week 2 (after one week of Suvorexant) and week 4 (after three weeks of Surovexant)

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.