ACT_for Alcohol Use Disorder and Depression

NCT06620276 | Recruiting

• 1 other identifier: 2025-12519
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Alcohol use disorders (AUDs) and depressive disorders frequently coexist, complicating the clinical management of patients suffering from them. Taken separately, these two disorders have a significant prevalence in the population, and a recent meta-analysis concluded that coexistence could reach 1 in 5 patients (20.8%). This comorbidity represents a considerable challenge, particularly in cases of treatment-resistant depression (TRD), where patients do not respond to conventional pharmacological interventions. Since alcohol can act as a powerful trigger for depressive symptoms, and conversely, a depressive state increases the risk of alcohol abuse, the question of intervention sequence is also of clinical interest: should priority be given to treating TRD, AUD or both simultaneously? This question raises a major issue for healthcare professionals, as current conventional therapeutic approaches present limitations in the concomitant management of these complex disorders. Thus, in certain clinical settings, ketamine has emerged as a promising intervention to treat both TRD and AUD. In fact, ketamine has been shown to produce rapid but only transient antidepressant effects, and is part of the possible treatment arsenal for TRD. The potential of ketamine in the treatment of AUD has also been explored in recent studies, with a few small randomized controlled trials. In these trials, the combination of ketamine with psychotherapy, versus placebo, was investigated as a means of alleviating AUD. Ketamine was shown to increase abstinence rates, time to relapse and decrease the number of heavy drinking days. Acceptance and Commitment Therapy (ACT) is a form of cognitive-behavioural therapy that emphasizes psychological flexibility and acceptance of difficult emotions and thoughts without judgment, a type of psychotherapy particularly relevant to AUD. Thus, adding ACT to ketamine treatment could increase the duration of ketamine's effect on depressive symptoms, while reducing AUD. In view of this accumulated evidence of the potential benefit of ketamine and ACT, adding acceptance and commitment therapy to ketamine appears to be a promising option for improving outcomes in patients diagnosed with TRD comorbid with AUD. This study will not only verify the feasibility of this type of intervention in this particular patient population, but also the preliminary effects on their alcohol consumption and depressive symptoms.

Conditions

Depression - Major Depressive Disorder; Alcohol Use Disorder

Keywords

Depression; Psychotherapy; Alcohol Use Disorder; Ketamine-assisted Acceptance and Commitment Therapy

Outcome Measures

Primary Outcomes (1)

• Study completion AND Adherence to ketamine infusions and ACT psychotherapy sessions

  The number of patients who complete the study (phase 1, weeks 0 to 12). Hypothesis is that at least 80% of enrolled participants will complete the study (week 12 visit). The number of patients who complete all ketamine infusions and ACT psychotherapy sessions (weeks 1 to 8). Hypothesis is that at least 80% of enrolled participants will receive at least 75% of all scheduled ketamine infusions and ACT psychotherapy sessions.

  From enrollment to the end of the follow-up at 12 weeks (phase 1, weeks 0 to 12) and from week 1 to week 8

Secondary Outcomes (10)

• Systematic tracking of adverse events and serious adverse events (Safety)

  From enrollment to the end of treatment at 8 weeks

• Recruitment rate

  Before enrollment

• Consent rate

  Before enrollment

• Data collection rate

  From enrollment to the end of treatment at 8 weeks

• Resource utilization - Therapist

  From enrollment to the end of treatment at 8 weeks

Other Outcomes (16)

• Change From Baseline in Alcohol Use (TLFB) to End of Treatment and to Follow-up

  From enrollment to the end of the follow-up (6 months)

• Change From Baseline in Alcohol Craving (ACQ-NOW) to End of Treatment and to Follow-up

  From enrollment to the end of the follow-up (6 months)

• Change From Baseline in Alcohol Craving (OCDS) to End of Treatment and to Follow-up

  From enrollment to the end of the follow-up (6 months)

Study Arms (1)

Ketamine-assisted Acceptance and Commitment Therapy

EXPERIMENTAL

30 consecutive participants who will receive 6 infusions of ketamine and 8 sessions of Acceptance and Commitment Therapy (ACT) at our research site.

Behavioral: Acceptance and Commitment Therapy; Drug: Ketamine

Interventions

Ketamine DRUG

The protocol includes 6 IV ketamine infusions over 4 weeks at the CHUM Neuromodulation Unit, following the Montreal Model integrating psychotherapeutic and contextual elements (e.g. preparation, music, and integration). Infusions occur twice weekly in weeks 3 and 4 of the treatment protocol, then once weekly in weeks 5 and 6. The first dose is 0.5 mg/kg in 250 mL saline over 40 minutes, with possible titration up to 1.0 mg/kg based on tolerability, clinical response, and participant preferences. Blood alcohol level is measured by breathalyzer before each session, and if any detectable alcohol is present (i.e., BAC ≠ 0%), the infusion will be postponed and rescheduled. Infusions occur in a quiet, dim room with continuous monitoring. Before each infusion, a brief mindfulness exercise promotes openness to internal experience. During the infusion, participants listen to a curated 60 minute instrumental playlist to support emotional exploration.

Ketamine-assisted Acceptance and Commitment Therapy

Acceptance and Commitment Therapy BEHAVIORAL

The ACT intervention consists of eight weekly 50 minute sessions, delivered in person when possible, with virtual options available. ACT targets psychological flexibility by addressing fusion, evaluation, avoidance, and reason giving through six core processes: acceptance, values, committed action, present moment awareness, cognitive defusion, and self as context. Sessions combine didactic content and experiential exercises following a standardized manual, with therapists trained in ACT. Participants receive a workbook to support practice. Each session begins with a brief mindfulness exercise that evolves across weeks, starting with grounding and simple emotional labeling, then progressing to neutral sensory descriptions and openness to challenging sensations.

Ketamine-assisted Acceptance and Commitment Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent after reading and understanding the patient information handout
• Alcohol Use Disorder (AUD) diagnosed by a trained psychiatrist
• Diagnosis of treatment resistant unipolar or bipolar depression, defined as failure to respond to ≥2 adequate trials per Canadian national depression guidelines
• Willingness to engage in 8 weekly psychotherapy sessions
• No changes to psychotropic medications during treatment
• Average daily ethanol consumption of at least moderate risk as per WHO risk levels (Men: \>40 to 60 g per day or \>2.9 to 4.3 drinks / Women: \>20 to 40 g per day or \>1.4 to 2.9 drinks)
• Bipolar or unipolar depressive episode (DSM5), current episode, with MADRS ≥ 20
• Age 18 to 70 years
• Agreement to abstain from consuming grapefruit juice on ketamine infusion days
• Agreement to abstain from driving or operating heavy machinery after infusions until the next day

You may not qualify if:

• Current participation in other evidence based psychotherapeutic interventions for mood disorders or substance abuse
• Inability to commit to the study protocol due to professional or personal obligations
• Non English or non French speaking
• Psychiatric comorbidity likely to take precedence over AUD or TRD
• Acute psychotic disorder or acute psychotic symptoms
• Current or prior substance abuse or dependence other than AUD (except caffeine or nicotine)
• Non response to esketamine or ketamine during the current depressive episode
• Known intellectual disability or autism spectrum disorder
• Inability to attend regular visits to the CHUM Neuromodulation clinic
• Depression secondary to stroke, cancer, or severe medical conditions
• Risk factors for intracranial hemorrhage (trauma, aneurysm, neurosurgery)
• Uncontrolled hypertension or significant coronary or cerebrovascular disease
• Renal or hepatic impairment
• Pregnant, lactating, or of childbearing potential without approved contraception use during ketamine treatment, with a negative urine pregnancy test required at baseline
• Abnormal liver function tests (AST or ALT ≥ 3 times upper normal limit)

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2X3E4, Canada

RECRUITING

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MeSH Terms

Conditions

Alcoholism; Depression

Interventions

Acceptance and Commitment Therapy; Ketamine

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Nicolas Garel, MD MSc

  Centre Hospitalier d'Université de Montréal

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicolas Garel, MD MSc

CONTACT

514-890-8000; nicolas.garel.med@ssss.gouv.qc.ca

Samuel Cyr, PhD

CONTACT

514-890-8000; samuel.cyr.chum@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Assessing the feasibility of providing Acceptance and Commitment Therapy (ACT) to patients diagnosed with Alcohol Use Disorder and Treatment-Resistant Depression who are undergoing ketamine sessions.

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: October 1, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)