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

Marianne Goodman

Status and phase: Enrolling; Phase 2

Conditions: Suicide Risk; Major Depressive Disorder (MDD)

Treatments: Drug: Suvorexant (dual orexin receptor antagonist)

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT06854224

1851192

Details and patient eligibility

About

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)

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

Suvorexant group

Experimental group

Description:

Veteran patients with Major Depressive Disorder and elevated risk of suicide will receive the FDA-approved drug Suvorexant (brand name: Belsomra), a mixed Orexin antagonist, for four weeks. Participants will take 10mg of Surovexant nightly for the first two weeks and 20mg of Surovexant nightly for the second two weeks.

Treatment:

Drug: Suvorexant (dual orexin receptor antagonist)