ACT_for Alcohol Use Disorder 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

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder; Depression - Major Depressive Disorder
• Intervention / Treatment: Behavioral: Acceptance and Commitment Therapy; Drug: Ketamine

Detailed Description

Study rationale: Acceptance and Commitment Therapy (ACT) has been proposed as a particularly well-suited form of psychotherapy to be added to ketamine for improving its rapid but short antidepressant action. This is in part because of ketamine's acute effect on psychological flexibility, a crucial construct that is addressed with ACT. / There has been extensive efforts to find effective strategies to enhance and sustain the therapeutic response of ketamine, with most attempts using various pharmacotherapies such as clonidine, D-cycloserine, lamotrigine, lithium, rapamycin, and riluzole which have yielded mostly disappointing results. Consequently, the most common approach to extending ketamine benefits has been to administer repeated doses, although there is limited evidence supporting the long-term safety, efficacy, and practicality of this practice. / Substantial evidence indicates that psychotherapy can enhance the effects of pharmacological treatments, such as oral antidepressants, and even help maintain their benefits after discontinuation. While further research is required, it is plausible to assume that similar benefits of adding psychotherapy could extend to ketamine, particularly considering its potential neuroplastic effects. / In view of the accumulated evidence, the addition of ACT to a ketamine intervention appears as a promising option to improve the outcomes of patients diagnosed with AUD comorbid with TRD. This study will not only verify the feasibility of adding psychotherapy to ketamine in this population, but also the effect on their alcohol consumption and depressive symptoms. / Background: Alcohol Use Disorder (AUD) and depressive disorders frequently coexist and complicate the clinical management and treatment outcomes for patients. It is estimated that around 1 in 10 people (10.4%) in the USA is experiencing a major depressive disorder (MDD) in the course of a year, while it goes up to 1 in 5 (20.6%) in the course of a lifetime. As for AUD, twelve month and lifetime prevalence are respectively 13.9% and 29.1%. When these disorders coexist, the prevalence is estimated as high as 20.8%, as reported by a recent meta-analysis. Research has also shown that individuals with AUD are approximately 2.3 times more likely to experience MDD within a given year. / This comorbidity presents a formidable challenge, particularly in cases of Treatment-Resistant Depression (TRD), a subset of MDD where patients do not respond to conventional pharmacological interventions. In the United States, it is estimated that out of 8.9 million adults receiving medication for MDD, 2.8 million, or 30.9%, are grappling with TRD. The economic impact is substantial, with the total annual cost of medication-treated MDD reaching $92.7 billion, nearly half of which $43.8 billion or 47.2% is attributable to TRD. / The concomitance of TRD and AUD represents a major clinical challenge as alcohol can act as a powerful trigger for depressive symptoms, and conversely a depressive state can increase the risk of alcohol abuse. This creates a complex, bidirectional relationship between the two disorders, considerably complicating the assessment and clinical management of these concurrent disorders. The question of intervention sequence is also of clinical interest: should treatment of TRD, AUD, or both simultaneously be prioritized? This question raises major challenges for health professionals, as current conventional therapeutic approaches present limitations in the concomitant management of these complex disorders. Traditional pharmacological treatments, such as antidepressants, may not be sufficiently effective or tolerated by some patients to treat these comorbid disorders. As for standard psychotherapeutic approaches, such as cognitive-behavioral therapy, the heterogeneity of symptoms and diversity of issues often mean that the needs of individuals suffering from these comorbidities cannot be met comprehensively. / In response to this challenge, in selected clinical settings, ketamine has emerged as a promising intervention for treating both AUD and depressive disorders. Ketamine, an NMDA receptor antagonist, has been shown to produce rapid and substantial, albeit short-lived (i.e. 7 days), antidepressant effects in individuals with TRD. Furthermore, ketamine potential in treating AUD has been explored in recent studies, with randomized controlled trials emerging. In such trials, the combination of ketamine to psychotherapy as compared to a placebo is studied to alleviate AUD. For instance, individuals with AUD who received a ketamine infusion and motivational therapy had improved rates of abstinence, prolonged time to relapse, and fewer days of heavy drinking than individuals with AUD who received an infusion of midazolam, considered as a placebo. Another team also compared the use of ketamine with a relapse prevention-based psychological therapy to placebo and found that there was a significant increase in the number of days abstinent from alcohol. / Considering the substantial but transient effect of ketamine on depressive symptomatology, and its promising results in AUD patients, a novel approach is to add a psychotherapeutic component to the ketamine treatment with the aim of enhancing and prolonging its effect. Acceptance and Commitment Therapy (ACT) seems to be a particularly well-suited form of psychotherapy to be added to ketamine treatment. Indeed, ACT is a form of cognitive-behavioural therapy that emphasizes psychological flexibility and the acceptance of difficult emotions and thoughts without judgment. ACT has been extensively studied in various psychopathologies, including anxiety and depression, demonstrating positive outcomes in multiple rigorous clinical trials and meta-analysis. Growing evidence suggest that ACT may be an effective and even superior treatment for individuals with substance use disorders. ACT encourages individuals to commit to behavior changes consistent with their values, which can be particularly beneficial for those with AUD and comorbid TRD. Ketamine has been shown to have an acute effect on psychological flexibility, and the addition of ACT's focus on acceptance and value-driven behavior holds promise for improving the ketamine's rapid and short antidepressant action and addressing the complex interplay of AUD and TRD. / Standard treatment options: Alcohol Use Disorder (AUD). In 2023, a committee of AUD specialists published the Canadian guideline with treatment recommendations for AUD. As a strong recommendation, they first proposed that all patients with AUD should be offered specialist-led psychosocial treatment interventions, such as cognitive behavioral therapy or family-based therapy. However, both therapies were found to have small to medium beneficial impacts on AUD outcomes. For pharmacotherapy, as a complement to the psychosocial treatment, naltrexone or acamprosate were recommended as first-line therapy. Second-line options, some of them being used as off-label therapies, were also proposed, namely gabapentin, topiramate and disulfiram. Of note, these recommendations are in line with other reviews of AUD pharmacotherapy and other national guidelines, namely American and Australian guidelines. / However, there are some limitations associated with the use of those treatment options. Apart from safety concerns, with common AE associated with treatments such as nausea, dizziness and fatigue, there is an ongoing debate among experts about the actual efficacy of the treatment options. In fact, naltrexone and acamprosate have an estimated number needed to treat to prevent a return to heavy drinking of 12, with modest differences found when comparing drugs with placebo, contributing to their underutilization in AUD patients. For instance, in over 28,000 Medicare beneficiaries hospitalized with a primary or secondary diagnosis of AUD, it was found that only 0.7% of patients started pharmacotherapy within two days after discharge and 1.3% within 30 days. Even among patients for whom AUD was the primary diagnosis after hospitalization, only 2.3% started pharmacotherapy within two days of discharge. / Treatment Resistant Depression (TRD). Leading experts in TRD summarized in 2023 the options available to try and reach a favorable outcome in individuals who fail to respond to at least two adequate trials of psychotropics against depression. First, extending a current antidepressant trial could be a potential treatment plan. A systematic review determined that up to 20% of patients who did not respond to their antidepressant in the first four weeks of treatment responded during the following four weeks (from weeks five to eight), and up to 10% during weeks nine to twelve. Similarly, there is some evidence, albeit conflicting, that switching antidepressants or combining antidepressants could benefit some patients, especially if the change or addition involves a new mechanism of action. To cite only one example of this option, adding antidepressants with antagonism activity on the alpha-2 receptor (i.e., mirtazapine, trazodone) to a selective serotonin reuptake inhibitor was superior to monotherapy in a meta-analysis. / Other treatment modalities have also been studied, including adding various pharmacological agents like second-generation antipsychotics and mood stabilizers. In real-world settings, most patients with TRD are prescribed multiple psychotropic medications, often for extended periods, with generally limited success. For example, a recent cohort study conducted over 12 months across various European countries, involving 411 patients with TRD, highlighted high rates of polypharmacy alongside modest clinical improvement, with only about 30% showing a positive response after 6 to 12 months of consistent treatment. The study also indicated a concerning level of therapeutic inertia, where 60% of patients did not undergo any changes in their treatment plan, despite ongoing poor outcomes. / Electroconvulsive therapy (ECT), aside from the usual pharmacological approaches, is considered one of the most empirically supported interventions for TRD. However, despite its effectiveness, ECT is often hindered by significant barriers, including societal stigma, inconsistent access, and notable side effects such as memory loss, largely due to the need for general anesthesia during the procedure. / Amid the current treatment challenges, the rapid and robust antidepressant effects of subanesthetic doses of IV racemic ketamine, a distinctive N-methyl-D-aspartate (NMDA) receptor antagonist, have sparked considerable interest and optimism. Meta-analyses suggest that nearly half of patients with treatment-resistant depression (TRD) experience a significant reduction in depressive symptoms, over 50%, within just hours to days following a single 40-minute IV ketamine infusion. This promising efficacy has led many experts to regard subanesthetic ketamine as one of the most transformative advancements in psychiatric pharmacology in recent decades. While impressive, ketamine's benefits typically fade within days or weeks. / Given the evidence of ketamine's beneficial effect, the neuromodulation service of the CHUM began providing this treatment to patients with TRD in 2018, covering the whole province of Quebec. Since then, the neuromodulation service has created a state-of-the-art infrastructure for the ketamine service. / *Data Sharing Statement: Reasonable requests for access to data will be reviewed by the study's steering committee, and, if approved, only the data necessary to complete the proposed project will be shared under a data use agreement.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nicolas Garel, MD MSc; Phone Number: 514-890-8000; Email: nicolas.garel.med@ssss.gouv.qc.ca
• Study Contact Backup: Name: Samuel Cyr, PhD; Phone Number: 514-890-8000; Email: samuel.cyr.chum@ssss.gouv.qc.ca

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H2X3E4
      • Recruiting
      • Centre Hospitalier de l'Universite de Montreal
      • Contact: Nicolas Garel, MD MSc; Phone Number: 514-890-8000; Email: nicolas.garel.med@ssss.gouv.qc.ca
      • Contact: Samuel Cyr, PhD; Phone Number: 514-890-8000; Email: samuel.cyr.chum@ssss.gouv.qc.ca
      • Principal Investigator: Nicolas Garel, MD MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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.

Behavioral: 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.; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systematic tracking of adverse events and serious adverse events (Safety)	Safety will be assessed through systematic tracking of adverse events (AEs) and serious adverse events (SAEs). AEs occurring during or after ketamine/psychotherapeutic sessions will be solicited and recorded at each study visit according to Medical Dictionary for Regulatory Activities (MedDRA) standards. Hypothesis that it will be safe and tolerated, with no SAEs	From enrollment to the end of treatment at 8 weeks
Recruitment rate	The recruitment rate will be calculated as the number of participants enrolled per month. This metric will reflect the feasibility of enrolling eligible individuals within the study timeline. A recruitment rate of 2 to 3 participants per month is anticipated, with full recruitment expected within 10-12 months.	Before enrollment
Consent rate	The consent rate will represent the proportion of eligible participants who agree to enroll. A consent rate exceeding 80% will be considered indicative of the study's acceptability among the target population.	Before enrollment
Data collection rate	The data collection rate will be defined as the proportion of planned data successfully collected across all participants. A rate above 80% will indicate that data collection methods are both feasible and acceptable to participants.	From enrollment to the end of treatment at 8 weeks
Resource utilization - Therapist	Resource utilization will be systematically tracked throughout the study. For each participant, the following metric will be recorded: therapist time for preparation, delivery, and documentation of ACT sessions. This can help determine whether the intervention is feasible in terms of resource allocation.	From enrollment to the end of treatment at 8 weeks
Resource utilization - Clinical staff	Resource utilization will be systematically tracked throughout the study. For each participant, the following metric will be recorded: clinical staff time dedicated to ketamine infusions, including nursing, medical monitoring, and recovery supervision. This can help determine whether the intervention is feasible in terms of resource allocation.	From enrollment to the end of treatment at 8 weeks
Resource utilization - Session duration	Resource utilization will be systematically tracked throughout the study. For each participant, the following metric will be recorded: session duration for both psychotherapy and infusions. This can help determine whether the intervention is feasible in terms of resource allocation.	From enrollment to the end of treatment at 8 weeks
Resource utilization - Material and infrastructure	Resource utilization will be systematically tracked throughout the study. For each participant, the following metric will be recorded: material and infrastructure use, including room occupancy time, ketamine dosing supplies, monitoring equipment, and music delivery devices. This can help determine whether the intervention is feasible in terms of resource allocation.	From enrollment to the end of treatment at 8 weeks
Resource utilization - Administrative and coordination time	Resource utilization will be systematically tracked throughout the study. For each participant, the following metric will be recorded: administrative and coordination time, such as scheduling, safety checks (e.g., breathalyzer), and follow-up communication. This can help determine whether the intervention is feasible in terms of resource allocation.	From enrollment to the end of treatment at 8 weeks
Number of patients engaging in ACT in between therapy exercises	Participant engagement with ACT outside of scheduled therapy sessions will be assessed as a secondary effectiveness measure. This will be defined by the number of between-session exercises completed.	From enrollment to the end of treatment at 8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Alcohol Use (TLFB) to End of Treatment and to Follow-up	With the Timeline Followback method, study team provide calendar-based memory cues to help patients build up chronological reports of their alcohol use within an established period. It is considered the gold-standard method to assess alcohol use/quantity.	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	The Alcohol Craving Questionnaire - Now (ACQ-NOW) is a 47-item, self-administered questionnaire designed to assess the intensity and characteristics of alcohol craving at the present moment. Items are rated on a Likert-type scale, and responses are summed to generate a total score, with higher scores indicating greater levels of alcohol craving.	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	The Obsessive Compulsive Drinking Scale (OCDS) is a 14-item, self-administered questionnaire designed to assess alcohol related thoughts and behaviors, including obsessive preoccupation with drinking and compulsive drinking behavior. Items are scored using ordinal response options and summed to yield total and subscale scores, with higher scores indicating greater severity of obsessive and compulsive drinking symptoms.	From enrollment to the end of the follow-up (6 months)
Change From Baseline in SOCRATES (readiness to change alcohol-related behaviors) Total Score to End of Treatment and to Follow-up	The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) is a 19-item, self-administered questionnaire designed to assess an individual's readiness to change alcohol related behaviors and engage in treatment. Items are summed to generate total and subscale scores reflecting recognition, ambivalence, and taking steps, with higher scores indicating greater readiness for change and treatment engagement.	From enrollment (baseline) to the end of the follow-up (6 months)
Change From Baseline in AASE (self-confidence to avoid alcohol use) Total Score to End of Treatment and to Follow-up	The Alcohol Abstinence Self Efficacy Scale (AASE) is a 12-item, self-administered questionnaire designed to assess an individual's confidence in their ability to abstain from alcohol across a range of high risk situations. Items are summed to produce a total score, with higher scores indicating greater abstinence self efficacy.	From enrollment (baseline) to the end of the follow-up (6 months)
Change From Baseline in MADRS (depressive symptoms) Total Score to End of Treatment and to Follow-up	The Montgomery-Åsberg Depression Rating Scale is a 10-item, clinician-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 6 (item's symptoms are severe). The total possible score is 60. Higher scores indicate greater severity.	From enrollment (baseline) to the end of the follow-up (6 months)
Change From Baseline in BDI-II (depressive symtpoms) Total Score to End of Treatment and to Follow-up	The Beck Depression Inventory Scale is a 21-item, patient-rated scale to rate the severity of the depressive symptoms. Each item is scored from 0 (item's symptoms not present) to 3 (item's symptoms are severe). The total possible score is 63. Higher scores indicate greater severity.	From enrollment (baseline) to the end of the follow-up (6 months)
Change From Baseline in GAD-7 (general anxiety symptoms) to End of Treatment and Follow-up	The General Anxiety Disorder=7 (GAD-7) is a 7 item, self administered measure with scores ranging from 0 to 21, where higher scores indicate worse anxiety symptoms.	From enrollment (baseline) to the end of the follow-up (6 months)
Change From Baseline in SSI (suicide ideation) Total to End of Treatment and follow-up	The Beck Scale for Suicide Ideation (SSI) is a 19 item, self administered measure with scores ranging from 0 to 38, where higher scores reflect more severe suicide related thoughts.	From enrollment (baseline) to the end of the follow-up (6 months)
The Mystical Experience Questionnaire (MEQ) after each ketamine treatment	The Mystical Experience Questionnaire consists of 30 statements to rate from 0 (none) to 5 (extreme). Possible scores range from 0 to 150 with higher scores indicating greater mystical experiences.	From the start of ketamine treatment to to the end of ketamine treatment (4 weeks)
The Emotional Breakthrough Inventory (EBI) after each ketamine treatment	The Emotional Breakthrough Inventory (EBI) is a 6-item, self-administered questionnaire designed to assess the experience of emotional release or breakthrough during psychedelic assisted psychotherapy. Items are rated using Likert-type response options and summed to produce a total score, with higher scores indicating a greater degree of emotional breakthrough.	From the start of ketamine treatment to to the end of ketamine treatment (4 weeks)
The Five Facet Mindfulness Questionnaire (FFMQ) at baseline	The Five Facet Mindfulness Questionnaire (FFMQ) is a 39-item, self-administered questionnaire designed to assess dispositional mindfulness across five domains, namely observing, describing, acting with awareness, non judging, and non reactivity to inner experience. Items are rated on a Likert-type scale and summed to generate total and facet scores, with higher scores indicating greater levels of mindfulness.	At enrollment (baseline)
The Modified Tellegen Absorption Scale (MODTAS) at baseline	The Modified Tellegen Absorption Scale (MODTAS) is a 34-item, self-administered questionnaire designed to assess absorption as a personality trait, reflecting an individual's openness to emotional and cognitive alterations across a range of situations. Items are summed to generate a total score, with higher scores indicating greater levels of absorption.	At enrollment (baseline)
Change From Baseline in EQ-5D-5L (quality of life) to End of Treatment and Follow-up	The EQ-5D-5L is a self-administered measure of health related quality of life consisting of two components, a five item descriptive system and a visual analog scale. The descriptive system assesses mobility, self care, usual activities, pain or discomfort, and anxiety or depression, each rated across five levels of severity from no problems to extreme problems. The visual analog scale captures the participant's self rated health on a vertical scale anchored by the worst and best health states imaginable, with higher scores reflecting better perceived health status.	From enrollment (baseline) to the end of the follow-up (6 months)
Change From Baseline in WHODAS 2.0 (functioning and disability) to End of Treatment and Follow-up	The WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) 12-item version is a self-administered questionnaire designed to assess overall functioning and disability. It evaluates functioning across six domains, including cognition, mobility, self care, interpersonal relationships, daily activities, and social participation. Items are summed to generate an overall functioning score, with higher scores indicating greater levels of disability.	From enrollment to the end of the follow-up (6 months)
Therapeutic Alliance for participants and for therapists	The Working Alliance Inventory for patient (WAI-SR) is a 12-item, self-administered questionnaire designed to assess the quality of the working alliance between the patient and the therapist. Items evaluate key aspects of the therapeutic alliance and are summed to produce a total score, with higher scores indicating a stronger working alliance. The Working Alliance Inventory - therapist version (WAI-SRT) is a 10-item, self-administered questionnaire completed by the therapist to assess the quality of the working alliance with the patient. Items are summed to yield a total score, with higher scores reflecting a stronger perceived therapeutic alliance.	From the start of psychotherapy treatment to to the end of treatment (8 weeks)

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Investigators: Principal Investigator: Nicolas Garel, MD MSc, Centre Hospitalier d'Université de Montréal

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: September 25, 2024
• First Submitted That Met QC Criteria: September 27, 2024
• First Posted (Actual): October 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Alcohol Use Disorder; Psychotherapy; Ketamine-assisted Acceptance and Commitment Therapy
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Behavior; Alcoholism; Depression; Organic Chemicals; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Cognitive Behavioral Therapy; Ketamine; Acceptance and Commitment Therapy
• Other Study ID Numbers: 2025-12519

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No