Suvorexant for Depression

Overseen By James Murrough, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Marianne Goodman

Must not be taking: CYP3A drugs, Digoxin

Disqualifiers: Substance use, Psychotic, Bipolar, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 4 weeks

30 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using certain medications like strong CYP3A liver enzymes, moderate CYP3A inhibitors, strong CYP3A inducers, or digoxin.

How does the drug Suvorexant differ from other treatments for depression?

Suvorexant is unique because it is primarily used as a sleep aid, working by blocking orexin receptors in the brain, which are involved in wakefulness. This mechanism is different from traditional antidepressants that typically target neurotransmitters like serotonin or norepinephrine. ^{1 2 3 4 5}

What is the purpose of this 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)

Eligibility Criteria

This trial is for veteran adults with Major Depressive Disorder and a high risk of suicide. Participants will take the drug Suvorexant daily for four weeks, with in-person visits at weeks 1, 3, and 5, plus remote self-reports at weeks 2 and 4.

Inclusion Criteria

Veteran

Lifetime suicide attempt history and suicidal ideation at baseline as determined by a score ≥2 on the Columbia-Suicide Severity Rating Scale (C-SSRS)

I have been diagnosed with Major Depressive Disorder by a psychiatrist.

Exclusion Criteria

Imminent suicidal or homicidal risk

I have a serious health or brain condition.

I am currently taking digoxin.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

Treatment

Participants take Suvorexant daily for four weeks, starting with 10mg for the first two weeks and 20mg for the last two weeks

4 weeks

3 visits (in-person) at weeks 1, 3, and 5; 2 remote assessments at weeks 2 and 4

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Suvorexant

Trial Overview The study tests the safety, feasibility, and tolerability of Suvorexant—a dual orexin receptor antagonist—in reducing suicidal thoughts among those with severe depression. The dosage increases from week two to four.

Participant Groups

Group I: Suvorexant group Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Marianne Goodman

Lead Sponsor

Trials

1

Recruited

30+

VISN 2 Mental Illness Research & Education Clinical Center

Collaborator

Trials

1

Recruited

30+

References

1. France pubmed.ncbi.nlm.nih.gov

Emodinol ameliorates urate nephropathy by regulating renal organic ion transporters and inhibiting immune inflammatory responses in rats. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Characterization of Stereoselective Metabolism, Inhibitory Effect on Uric Acid Uptake Transporters, and Pharmacokinetics of Lesinurad Atropisomers. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and safety of switching from febuxostat to dotinurad, a novel selective urate reabsorption inhibitor, in hyperuricemic patients with type 2 diabetic kidney disease: Protocol for a single-arm, open-label, prospective, exploratory study. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Pallidifloside D from Smilax riparia enhanced allopurinol effects in hyperuricemia mice. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Hypouricemic effect of allopurinol are improved by Pallidifloside D based on the uric acid metabolism enzymes PRPS, HGPRT and PRPPAT. [2017]