Clinical TrialDepressive DisordersKetamineNot yet recruiting

Ketamine-Enhanced Therapy for Individuals With Alcohol Use Disorder and Depression: A Pilot Study (KET-DUAL)

This Phase I/II, open-label, single-group trial (n=20) will assess the safety, feasibility and preliminary efficacy of ketamine-enhanced psychotherapy in adults with moderate-to-severe alcohol use disorder (AUD) and comorbid major depressive disorder (MDD). Participants will receive three sub-anaesthetic subcutaneous doses of racemic ketamine (0.7 mg/kg initially, with potential escalation up to 1.2 mg/kg at investigator discretion) combined with a manualised cognitive–behavioural therapy (CBT) programme adapted for ketamine-assisted treatment. The single-arm pilot consists of six 90-minute CBT sessions delivered over six weeks with ketamine dosing at weeks 2, 4 and 6; week 1 is preparation, integration sessions occur 24–48 hours after each dose, and continued CBT occurs in the intervening weeks. Primary outcomes are feasibility (recruitment rates, retention, session attendance and treatment adherence) and safety (frequency, severity and relatedness of adverse events including dissociation, affective destabilisation and vital-sign abnormalities), with preliminary clinical measures of alcohol consumption, depressive symptoms and treatment engagement assessed across a 22-week study period.

Target Enrollment
20 participants
Study Type
Phase I/II interventional
Design
Non-randomized

Detailed Description

To assess the safety, feasibility and preliminary efficacy of ketamine-enhanced therapy (KET) for alcohol use disorder (AUD) and comorbid major depressive disorder (MDD) in an open-label, single arm, pilot clinical trial.

Study Arms & Interventions

Ketamine-enhanced therapy (KET): sub-anesthetic ketamine plus structured psychotherapy

experimental

1. x CBT session (Week 1) Dose 1: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability) (Week 2) 2. x CBT sessions (Week 2 - 3) Dose 2: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability (Week 4) 2 x CBT sessions (Week 4 - 5) Dose 3: 1x Sub-anaesthetic subcutaneous dose of racemic ketamine (initially 0.7mg/kg, up to a potential maximum of 1.2mg/kg, at the discretion of the principal investigator and permitted based on tolerability (Week 6) 1x CBT session (Week 6)

Interventions

  • Ketamine

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • 1. Moderate to severe AUD according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria
  • 2. Presence of current Major Depressive Disorder (MDD), according to the Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) criteria
  • 3. Expressed motivation to reduce or cease alcohol consumption.
  • 4. Consumed at least 21 standard drinks per week or 2 HDD per week (≥5 standard drinks/day for men; ≥4 for women) in the month prior to screening
  • 5. Age 18-70
  • 6. Adequate cognition and English language skills to give valid consent and complete research interviews
  • 7. Stable housing
  • 8. Willingness to give written informed consent.
  • 9. Willingness to comply with study procedures and attend scheduled visits.

Exclusion Criteria

  • 1. DSM-5 diagnosis of current or past psychotic disorder, bipolar I disorder, or substance-induced psychosis.
  • 2. Current acute suicidality, defined as high risk by the Columbia Suicide Severity Rating Scale (C-SSRS) or clinical judgment or attempts in the past 6 months.
  • 3. DSM-5 diagnosis of current or past moderate-to-severe ketamine or other dissociative drug use disorder.
  • 4. Use of ketamine (prescribed or non-prescribed) in the previous 4 weeks.
  • 5. Enrolment in another interventional clinical trial that may interfere with safety, data quality, or trial participation.
  • 6. Pregnant or breastfeeding, or planning to become pregnant during the course of the study.
  • 7. Significant uncontrolled medical conditions, including but not limited to:
  • * Severe or poorly controlled hypertension (\>160/100 mmHg)
  • * Severe cardiovascular disease (e.g., heart failure, recent myocardial infarction, dysrhythmia)
  • * History of stroke, cerebral trauma, or intracranial mass/haemorrhage
  • * Severe hepatic impairment (e.g., MELD ≥10) or end-stage liver disease, bladder or kidney disease
  • 8. Clinically significant alcohol withdrawal at screening (e.g., CIWA-Ar ≥10, history of delirium tremens).
  • 9. History of heightened intracranial pressure, seizures, or diagnosed seizure disorder (except childhood febrile seizures).
  • 10. Known hypersensitivity to ketamine or any excipients.
  • 11. Concurrent use of psychotropic medications (other than stable-dose antidepressants ≥4 weeks).
  • 12. Active substance use disorder (moderate or severe) other than nicotine or caffeine; stable opioid use disorder permitted if on maintenance therapy (with strict stability criteria).
  • 13. Inability or unwillingness to comply with study procedures, judged by the principal investigator.
  • 14. Any clinically significant medical or psychiatric condition that, in the judgment of the Principal Investigator, poses a safety risk or could confound study results or hinder protocol adherence.

Study Details

  • Status
    Not yet recruiting
  • Phase
    Phase IPhase II
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment20 participants
  • Timeline
    Start: 2025-12-10
    End: 2027-12-10
  • Compound
    Ketamine
  • Topic
    Depressive Disorders

Study Team

Sponsors & Collaborators

Locations

Drug Health Services, Royal Prince Alfred Hospital — Sydney, New South Wales, Australia

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