Ketamine for the Rapid Treatment of Major Depressive Disorder and Alcohol Use Disorder
Sponsored by VA Office of Research and Development
About This Study
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.
Conditions Studied
Interventions
- •Ketamine + Naltrexone
- •Ketamine + Placebo
- •Placebo (psychoactive placebo midazolam) + Placebo
Eligibility
View full 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