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

VA Office of Research and Development

Status and phase: Completed; Phase 2; Phase 1

Conditions: Major Depressive Disorder; Alcohol Use Disorder

Treatments: Drug: Ketamine + Placebo; Drug: Placebo (psychoactive placebo midazolam) + Placebo; Drug: Ketamine + Naltrexone

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT02461927

MHBB-009-16F

GY 0002 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 65 patients

Sex: All

Ages: 21 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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65 participants in 3 patient groups, including a placebo group

Ketamine + Naltrexone

Experimental group

Description:

Subjects in this arm will receive (1) intravenous ketamine treatment once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular naltrexone once a month (a total of 2 injections).

Treatment:

Drug: Ketamine + Naltrexone

Ketamine + Placebo

Experimental group

Description:

Subjects in this arm will receive (1) intravenous ketamine treatment once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular placebo once a month (a total of 2 injections).

Treatment:

Drug: Ketamine + Placebo

Placebo (psychoactive placebo midazolam) + Placebo

Placebo Comparator group

Description:

Subjects in this arm will receive (1) intravenous placebo treatment (psychoactive placebo midazolam) once a week for 4 weeks (a total of 4 infusions) with a follow-up of 4 weeks and (2) intramuscular placebo once a month (a total of 2 injections).

Treatment:

Drug: Placebo (psychoactive placebo midazolam) + Placebo