Clinical TrialMajor Depressive Disorder (MDD)KetamineKetaminePlaceboPlaceboPlaceboCompleted

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

The investigators will compare 3 groups (ketamine + naltrexone vs ketamine alone vs placebo) in an 8-week randomised, double-blind, placebo-controlled trial (n=65) of repeated IV ketamine (0.5 mg/kg weekly x4) for comorbid MDD and AUD.

Target Enrollment
65 participants
Study Type
Phase I/II interventional
Design
Randomized, quadruple Blind

Detailed Description

An open-label lead-in (n=5) will first test repeated IV ketamine (0.5 mg/kg weekly x4) for safety and preliminary efficacy with 4-week follow-up.

Following the lead-in, an 8-week randomised, double-blind, parallel-group trial (n=60 planned; total n=65 actual) will compare IV ketamine (0.5 mg/kg weekly x4) plus monthly IM naltrexone (380 mg, 2 injections) versus ketamine plus IM placebo versus IV psychoactive placebo (midazolam 0.045 mg/kg) plus IM placebo; primary outcomes assess depression and alcohol-use measures with 4-month follow-up.

Study Protocol

Preparation

sessions

Dosing

4 sessions

Integration

sessions

Study Arms & Interventions

Ketamine + Naltrexone

experimental

IV ketamine once weekly x4 infusions plus IM naltrexone monthly x2 injections.

Interventions

  • Ketamine0.5 mg/kg
    via IV• weekly• 4 doses total

    IV ketamine 0.5 mg/kg, once weekly for 4 infusions

  • Compound380 mg
    via IM• monthly• 2 doses total

    Naltrexone 380 mg IM monthly, 2 injections

Ketamine + Placebo

experimental

IV ketamine once weekly x4 infusions plus IM placebo monthly x2 injections.

Interventions

  • Ketamine0.5 mg/kg
    via IV• weekly• 4 doses total

    IV ketamine 0.5 mg/kg, once weekly for 4 infusions

  • Placebo
    via IM• monthly• 2 doses total

    IM placebo monthly, 2 injections

Midazolam placebo + Placebo

inactive

IV psychoactive placebo midazolam once weekly x4 infusions plus IM placebo monthly x2 injections.

Interventions

  • Placebo0.045 mg/kg
    via IV• weekly• 4 doses total

    Psychoactive placebo midazolam 0.045 mg/kg IV, once weekly for 4 infusions

  • Placebo
    via IM• monthly• 2 doses total

    IM placebo monthly, 2 injections

Participants

Ages
21 – 65
Sexes
Male & Female

Inclusion 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

  • 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

Study Details

Locations

VA Connecticut Healthcare System West Haven Campus, West Haven, CT — West Haven, Connecticut, United States

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