Phase 2 Completed N=65 Randomized Quadruple-blind Treatment

Ketamine for the Rapid Treatment of Major Depressive Disorder and Alcohol Use Disorder

Major Depressive Disorder · Alcohol Use Disorder

Source: ClinicalTrials.gov NCT02461927 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Apr 2025

Primary outcomePrimary: Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline — 15; 9; 13 Participants

Summary

The investigators will compare 3 treatment groups (ketamine plus naltrexone vs. ketamine alone vs. placebo) for treating major depressive disorder (MDD) and alcohol use disorder (AUD) in an 8-week randomized, double-blind, placebo-controlled, between-subjects trial. First, prior to the double-blind trial, the investigators will conduct an open-label trial that will include 5 patients with comorbid MDD and AUD to test safety and efficacy of repeated ketamine treatment (0.5 mg/kg; once a week for 4 weeks; a total of 4 ketamine infusions) with a follow-up of 4 weeks. Second, after reviewing the safety and efficacy of repeated ketamine treatment from the open-label trial, the investigators will conduct an 8-week, randomized, double-blind, placebo-controlled trial that will include 60 patients with comorbid MDD and AUD to test safety and efficacy of repeated ketamine treatment (0.5 mg/kg; once a week for 4 weeks; a total of 4 ketamine infusions) plus naltrexone with a follow-up of 4 weeks. The 4-month follow-up session will also occur.

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline	15; 9; 13	—
PRIMARY Rate of Complete Abstinence From Alcohol	3; 6; 2	—

Eligibility Criteria

Inclusion Criteria

Male or female veterans and civilians, 21-65 years old
Current major depressive disorder without psychotic features by DSM-5 (antidepressant regimens can be allowed and changed during the trial)
Montgomery-Asberg Depression Rating Scale (MADRS) 20 or higher
A minimum of 4 of 11 current alcohol use disorder symptoms by DSM-5
Heavy drinking at least 4 times in the past month ('heavy drinking' defined as 5 standard drinks per day for men and 4 standard drinks per day for women
Able to provide written informed consent

Exclusion Criteria

Current substance use disorder by DSM-5 in the past 3 months (except alcohol, tobacco, or cannabis)
Current or past history of psychotic features or psychotic disorder
Current dementia
Current uncontrolled hypertension (systolic BP > 170 mm Hg or diastolic BP > 100 mm Hg)
Unstable medical condition or allergy to ketamine, midazolam, naltrexone, or lorazepam---clinically determined by a physician
Imminent suicidal or homicidal risk
Pregnant or nursing women, positive pregnancy test, or inadequate birth control methods in women of childbearing potential
Positive opioid or illicit drug screen test (except marijuana)
Opioid use within 10 days prior to study medication (injectable naltrexone) or risks for opioid use during the study
Liver enzymes that are three times higher than the upper limit of normal
Current use of benzodiazepine
Acute narrow-angle glaucoma
Severe sleep apnea---clinically determined by a physician

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02461927). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.