Ketamine paired with Acceptance and Commitment Therapy for people with alcohol problems and depression
Acceptance and Commitment Therapy in Patients With Alcohol Use Disorder and Comorbid Treatment-Resistant Depression Who Are Undergoing Ketamine Intervention: A Feasibility Study
This will test whether combining ketamine infusions with Acceptance and Commitment Therapy helps adults who have both alcohol use disorder and treatment-resistant depression.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | Centre hospitalier de l'Université de Montréal (CHUM) Academic / other |
| Locations | 1 site (Montreal, Quebec) |
| Trial ID | NCT06620276 on ClinicalTrials.gov |
What this trial studies
Adults with co-occurring alcohol use disorder and treatment-resistant unipolar or bipolar depression will receive a combined intervention of ketamine infusions plus eight weekly Acceptance and Commitment Therapy sessions at a single academic center. Eligible participants must meet DSM-5 criteria, have a current depressive episode with MADRS ≥20, have failed ≥2 adequate antidepressant trials, and meet WHO thresholds for at least moderate-risk drinking. Medications must remain stable during treatment, and participants must agree to abstain from grapefruit juice on infusion days and avoid driving until the next day. Outcomes include changes in depressive symptoms, alcohol use, and measures of psychological flexibility to assess feasibility and preliminary clinical effect.
Who should consider this trial
Good fit: Ideal candidates are adults 18–70 with DSM-5 alcohol use disorder and treatment-resistant unipolar or bipolar depression (MADRS ≥20 and ≥2 failed antidepressant trials) who drink at or above WHO moderate-risk levels and can attend eight weekly therapy sessions and ketamine infusion visits.
Not a fit: People without treatment-resistant depression, those drinking below the study's risk thresholds, or those with medical or psychiatric contraindications to ketamine or inability to attend in-person therapy are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could produce faster reductions in depressive symptoms and help sustain those improvements while reducing harmful alcohol use by pairing ketamine's rapid effects with ACT skills.
How similar studies have performed: While ketamine has well-documented rapid antidepressant effects and psychotherapy has been shown to extend pharmacologic benefits, combining ketamine with ACT for co-occurring AUD and treatment-resistant depression is a relatively new approach with limited direct evidence to date.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Montreal, Quebec
- Centre Hospitalier de l'Université de Montréal — Montreal, Quebec, Canada (Recruiting)
Study contacts
- Principal investigator: Nicolas Garel, MD MSc — Centre Hospitalier d'Université de Montréal
- Study coordinator: Nicolas Garel, MD MSc
- Email: nicolas.garel.med@ssss.gouv.qc.ca
- Phone: 514-890-8000
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.