NCT07247370

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

An Open-label Pilot Evaluation of Ketamine-Enhanced Psychotherapy in Individuals With Alcohol Use Disorder (AUD) and Co-morbid Major Depressive Disorder (MDD)

• Status: Not Yet Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: South West Sydney Local Health District · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed 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).

Conditions

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

Interventions

Type	Name	Description
DRUG	Ketamine	Subcutaneous administration of of Ketamine across 3 dosing sessions (at week 2, 4 and 6). Dosing adjustments are permitted based on tolerability, with a minimum dose of 0.7mg/kg and a potential maximum of 1.2 mg/kg, at the discretion of the principal investigator (previous studies have found efficacy at 0.8mg/kg for AUD).
BEHAVIORAL	Cognitive Behavioural Therapy	This study uses a manualized CBT program adapted for ketamine-assisted context. It integrates evidence-based CBT for substance use and depression with principles of psychedelic-assisted therapy, including "set and setting." considerations central to psychedelic-assisted therapy. The therapist manual includes guidance on psychological preparation, intention-setting, integration, and therapeutic framing of ketamine experiences. Participants receive six 90-minute sessions over six weeks, delivered by trained health professionals (e.g., psychologists, mental health nurses, social workers) with specific training in the adapted CBT protocol and psychedelic-assisted therapy. Sessions include: Preparation (Week 1): Review of alcohol use, treatment goals, and ketamine orientation. Integration (Weeks 2, 4, 6): Post-dose processing and linking experience to recovery goals occurring 24-48 hours post dose. Continued CBT (Weeks 3, 5): Coping strategies, goal setting, and relapse prevention.

Timeline

• Start date: 2025-12-10
• Primary completion: 2027-04-10
• Completion: 2027-12-10
• First posted: 2025-11-25
• Last updated: 2025-11-25

Locations

1 site across 1 country: Australia