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

Ketamine

Brief 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.

Intervention / Treatment

  • Ketamine + Naltrexone (DRUG)
    Subjects in this arm will receive (1) intravenous ketamine (0.5 mg/kg) once a week for 4 weeks (a total of 4 infusions) and (2) intramuscular naltrexone (380 mg) once a month (a total of 2 injections).
  • Ketamine + Placebo (DRUG)
    Subjects in this arm will receive (1) intravenous ketamine (0.5 mg/kg) once a week for 4 weeks (a total of 4 infusions) and (2) intramuscular placebo once a month (a total of 2 injections).
  • Placebo (psychoactive placebo midazolam) + Placebo (DRUG)
    Subjects in this arm will receive (1) intravenous psychoactive placebo midazolam (0.045 mg/kg) once a week for 4 weeks (a total of 4 infusions) and (2) intramuscular placebo once a month (a total of 2 injections).

Condition or Disease

  • Major Depressive Disorder
  • Alcohol Use Disorder

Phase

  • Phase 1
  • Phase 2

    • Study Design

    Study type: INTERVENTIONAL
    Status: Active, not recruiting
    Study results: No Results Available
    Age: 21 Years to 65 Years
    Enrollment: 65 (ACTUAL)
    Funded by: U.S. Fed
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    QUADRUPLE:
    • Participant
    • Care Provider
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Jan 01, 2015 ACTUAL
    Primary Completion: Oct 31, 2023 ESTIMATED
    Completion Date: Oct 31, 2023 ESTIMATED
    Study First Posted: Jun 03, 2015 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Aug 02, 2023

    Sponsors / Collaborators

    Lead Sponsor: VA Office of Research and Development
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    West Haven, Connecticut, USA

    Participant Groups

    • 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).

    • 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).

    • 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).

    Eligibility Criteria

    Sex: All
    Minimum Age: 21
    Maximum Age: 65
    Age Groups: Adult / Older Adult
    Healthy Volunteers: Yes

    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

    Primary Outcomes

    • Severity of depression

    • Rate of complete abstinence from alcohol

    More Details

    NCT Number: NCT02461927
    Other IDs: MHBB-009-16F
    Study URL: https://clinicaltrials.gov/study/NCT02461927
    Last updated: Sep 29, 2023