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

• Status: Recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: VA Connecticut Healthcare System; VA Office of Research and Development
• Treatments: Ketamine; Midazolam; Naltrexone

Criteria

Inclusion Criteria:

• 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