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

South West Sydney Local Health District

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Alcohol Use Disorder (AUD); Comorbidities and Coexisting Conditions; Major Depressive Disorder (MDD)

Treatments: Drug: Ketamine; Behavioral: Cognitive Behavioural Therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT07247370

X25-0138

Details and patient eligibility

About

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.

Full description

New strategies for the treatment of alcohol use disorder (AUD) and co-morbid major depressive disorder (MDD) are urgently required. This population represents a high-risk group that has largely been excluded from addiction-focused trials despite its clinical complexity and poor response to standard interventions.

Recent early phase studies have shown that ketamine-enhanced psychotherapy (KET) can reduce alcohol consumption, enhance motivation and alleviate depressive symptoms. Effects have been shown to be particularly pronounced among participants who also received motivational enhancement therapy, suggesting a synergistic effect between ketamine and psychotherapy.

Emerging evidence suggests that KET may be of promise for AUD, and has demonstrated a good safety profile and potential efficacy in alcohol dependence. However, no trials to date have specifically targeted AUD and co-morbid MDD.

This project will assess the clinical safety, feasibility and preliminary efficacy of KET in individuals with AUD and co-morbid MDD. The investigators hypothesise that KET will be safe and feasible to deliver in this population, and expect to observe preliminary improvements in alcohol consumption, depressive symptoms, and treatment engagement. The KET intervention is also anticipated to be well tolerated with high levels of session attendance and acceptable rates of adverse events.

The trial will utilise an open-label, single-arm, pilot clinical trial design. A sample of 20 individuals will receive 6 weeks of treatment including 6 manualized cognitive-behavioural therapy sessions and 3 dosing sessions with Ketamine administered at 2 week intervals (0.7mg/kg initially up).

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

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

Experimental group

Description:

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)

Treatment:

Behavioral: Cognitive Behavioural Therapy

Drug: Ketamine