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Completed

NCT Number: NCT02461927

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

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.

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Key information

Conditions

Major Depressive Disorder Alcohol Use Disorder Alcohol-Related Disorders Alcoholism Chemically-Induced Disorders Depressive Disorder Depressive Disorder, Major Mental Disorders Mood Disorders Substance-Related Disorders

Age range

21 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, 06516-2770, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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).

Primary outcomes

  1. Number of Participants With 50% or Greater Improvement in MADRS Scores From Baseline

    Time frame: Day 21 (after 4th infusion, 240 minutes)

    Our primary analysis (severity of depression) was to compare the proportions of subjects with clinical response in symptoms of major depressive disorder (response defined as a 50% or greater improvement from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores) at the end-of-treatment time point (Day 21, after 4th infusion, T+240 minutes).

  2. Rate of Complete Abstinence From Alcohol

    Time frame: Day 28

    Alcohol consumption was measured using the Time Line Follow Back (TLFB) method. The rates of complete abstinence from alcohol across visits 3 (day 0) through visit 7 (day 28) were compared among the three study groups.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Registry information

Official study title

Ketamine for The Rapid Treatment of Major Depression and Alcohol Use Disorder

Important dates

Study start
2015
Primary completion
2023
Study completion
2023
First posted
Jun 3, 2015
Registry last updated
Apr 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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