Recruiting

Ketamine & ACT

Sponsor:

Centre hospitalier de l'Université de Montréal (CHUM)

Code:

NCT06620276

Conditions

Depression - Major Depressive Disorder

Alcohol Use Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

Acceptance and Commitment Therapy

Ketamine

Study Details

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

Study ID

NCT06620276

Start date

May 1, 2025

Status verified date

Mar, 2026

Completion date

Jun 1, 2028

Anticipated

Primary completion date

Dec 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  • Clinically significant abnormal ECG results
  • Unstable thyroid hormone levels or uncorrected hypo or hyper thyroidism
  • Any unstable or clinically significant condition judged by the study physician to interfere with treatment
  • Positive toxicology screen for drugs not prescribed
  • Unwillingness to abstain from benzodiazepines, narcotics, or NMDA antagonists (including memantine and lamotrigine) 12 hours before infusions
  • Known intolerance or hypersensitivity to ketamine
  • Significant hearing impairment not improved by aids
  • Any recent significant decline in exercise tolerance

Study Design

Enrollment

30 participants

Anticipated

Intervention Model

Single group

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Ketamine-assisted Acceptance and Commitment Therapy

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

Interventions

Acceptance and Commitment Therapy

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

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.

Primary outcome measure

  • Study completion AND Adherence to ketamine infusions and ACT psychotherapy sessions [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

Nicolas Garel, MD MSc

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

Samuel Cyr, PhD

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

Locations

Centre Hospitalier de l'Université de Montréal

Recruiting

Montreal, Quebec, Canada, H2X3E4

Contacts

Nicolas Garel, MD MSc

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

Samuel Cyr, PhD

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

Principal Investigator:

Nicolas Garel, MD MSc

More Information

Sponsor

Centre hospitalier de l'Université de Montréal (CHUM)

Last update posted

Mar 5, 2026

Last verified

Mar, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Centre hospitalier de l'Université de Montréal (CHUM) on 2026-03-05.