This interventional trial (n=20) will assess the feasibility of combining Acceptance and Commitment Therapy (ACT) with ketamine intervention in patients with alcohol use disorder (AUD) and comorbid treatment-resistant depression (TRD).
Conducted by the Centre hospitalier de l’Université de Montréal (CHUM), this study aims to explore whether ACT can enhance and prolong the antidepressant effects of ketamine while also improving outcomes related to alcohol consumption.
Given the bidirectional relationship between AUD and TRD, and the limitations of conventional treatments, ketamine has emerged as a promising intervention. Prior research has demonstrated its rapid but transient antidepressant effects, as well as its potential in reducing alcohol use when combined with psychotherapy. By integrating ACT—a cognitive-behavioural therapy focused on psychological flexibility—this trial seeks to evaluate its impact on sustaining ketamine’s benefits and addressing the complex interplay of these conditions. The study is expected to begin in May 2025, with primary completion anticipated by November 2025.
Trial Details
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.Trial Number NCT06620276