ACT + Ketamine for Alcoholism and Depression

Overseen By Samuel Cyr, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

Must be taking: Psychotropics

Must not be taking: Benzodiazepines, Narcotics, NMDA antagonists

Disqualifiers: Other psychiatric comorbidity, Substance abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not change your medications during treatment. However, you must stop taking benzodiazepines the evening before ketamine infusions and discontinue any narcotics, memantine, or lamotrigine starting a minimum of 5 drug half-lives before infusions.

What data supports the effectiveness of the treatment Acceptance and Commitment Therapy (ACT) combined with ketamine for alcoholism and depression?

Research suggests that ketamine, when used with psychotherapy, shows promise in treating depression and substance use disorders. Ketamine-assisted therapy has been effective in improving depression and anxiety symptoms, and it may help reduce substance use when combined with psychological interventions like ACT. ^{1 2 3 4 5}

Is ketamine safe for use in humans when combined with therapy?

Ketamine has been used safely in humans for many years as an anesthetic and in lower doses for treating depression and alcohol use disorder. However, there are concerns about its effects on blood pressure, so it should be administered in a controlled setting with proper monitoring. ^{1 2 6 7 8}

How is the treatment ACT + Ketamine for Alcoholism and Depression different from other treatments?

ACT (Acceptance and Commitment Therapy) is unique because it focuses on increasing psychological flexibility by helping patients accept their thoughts and feelings rather than fighting them, and it encourages taking committed actions aligned with personal values. This approach is different from traditional therapies that often focus on changing thought patterns. When combined with ketamine, which is known for its rapid antidepressant effects, this treatment may offer a novel way to address both alcoholism and depression. ^{9 10 11 12 13}

Research Team

Nicolas Garel, MD MSc

Principal Investigator

Centre Hospitalier d'Université de Montréal

Eligibility Criteria

This trial is for individuals with both alcohol use disorder (AUD) and treatment-resistant depression (TRD), where traditional treatments haven't worked. It's aimed at those who struggle with alcohol as a trigger for depression or vice versa, and are looking for new ways to manage these conditions.

Inclusion Criteria

No changes to medications during treatment

Accept to abstain from consuming grapefruit juice on the day of the ketamine infusions

Have comorbid Alcohol Use Disorder (AUD) as diagnosed by a trained psychiatrist

Exclusion Criteria

Not able to commit to the study protocol secondary to professional/personal obligations

Other psychiatric comorbidity than MDD/TRD and AUD

Prior or current substance abuse or dependence other than AUD and/or recent history of cannabis abuse or dependence

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ketamine intervention combined with Acceptance and Commitment Therapy (ACT) for 8 weeks

8 weeks

8 sessions of ACT, in-person or virtual

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of depressive symptoms and alcohol use

6 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Acceptance and Commitment Therapy

Trial Overview The study tests adding Acceptance and Commitment Therapy (ACT) to ketamine treatment. ACT is a type of psychotherapy that helps patients accept their thoughts without judgment, which could extend the benefits of ketamine on depressive symptoms while also tackling AUD.

Participant Groups

Group I: Acceptance and Commitment Therapy (ACT) Experimental Treatment 1 Intervention

20 consecutive participants who will receive 8 sessions of Acceptance and Commitment Therapy (ACT) at our research site or virtually.

Who Is Running the Clinical Trial?

Centre hospitalier de l'Université de Montréal (CHUM)

Lead Sponsor

Trials

389

Recruited

143,000+

Findings from Research

Ketamine, traditionally used as an anesthetic since the 1970s, shows significant potential as a treatment for depression when combined with psychological therapies, based on both anecdotal evidence and clinical research.

The review proposes a novel approach to using esketamine (a specific form of ketamine) alongside Acceptance and Commitment Therapy (ACT), highlighting the importance of ketamine's psychoactive effects in enhancing therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Synergies of Ketamine and Psychotherapy. Mathai, DS., Mora, V., Garcia-Romeu, A.[2022]

A ketamine-assisted therapy program evaluated in a community of practice model showed significant improvements in mental health outcomes for 94 patients, with 91% reporting reduced anxiety, 79% reporting reduced depression, and 86% of PTSD patients screening negative after treatment.

The program demonstrated clinically significant enhancements in work/life functionality, with 92% of participants experiencing improvements, highlighting ketamine's potential as an effective treatment for those with treatment-resistant mental health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression. Dames, S., Kryskow, P., Watler, C.[2022]

Ketamine-assisted psychotherapy (KAP) shows a significant positive effect on treatment outcomes for substance use disorders (SUD), based on five randomized-controlled trials, although the results for treatment-resistant depression (TRD) were not beneficial in one study.

The efficacy of KAP may be linked to temporary neural changes from ketamine, such as NMDAR inhibition and increased synaptic neuroplasticity, but more research is needed to understand the mechanisms and to conduct larger clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active mechanisms of ketamine-assisted psychotherapy: A systematic review. Joneborg, I., Lee, Y., Di Vincenzo, JD., et al.[2022]

In a clinical trial, ketamine-assisted psychotherapy (KPT) significantly improved treatment outcomes for alcoholism, with 65.8% of patients achieving total abstinence for over a year, compared to only 24% in the conventional treatment group.

KPT appears to induce beneficial psychological changes, such as improved self-concept and life values, while also affecting neurotransmitter systems related to alcohol dependence, suggesting a multifaceted mechanism of action for its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. Krupitsky, EM., Grinenko, AY.[2022]

In a study of 831 Veterans receiving Acceptance and Commitment Therapy for depression (ACT-D), participants showed a significant average reduction in depression symptoms, with a 3.39 point decrease on the PHQ-9 scale, indicating moderate effectiveness.

40% of Veterans achieved subthreshold depression symptoms after treatment, suggesting that ACT-D can be beneficial for many, although adaptations may be necessary for those with comorbid conditions like PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Acceptance and Commitment Therapy for depression and predictors of treatment response in Veterans Health Administration patients. Grau, PP., Sripada, RK., Ganoczy, D., et al.[2023]

Acceptance and Commitment Therapy (ACT) significantly improved cumulative abstinence duration and reduced depression and anxiety symptoms in patients with alcohol use disorder (AUD) and comorbid affective disorders compared to treatment as usual (TAU) alone, based on a study of 52 participants.

The benefits of ACT were sustained over a 6-month follow-up period, indicating its effectiveness as an adjunct to standard treatment for enhancing recovery outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptance and Commitment Therapy in the Treatment of Alcohol Use Disorder and Comorbid Affective Disorder: A Pilot Matched Control Trial. Thekiso, TB., Murphy, P., Milnes, J., et al.[2018]

Acceptance and Commitment Therapy (ACT) effectively enhances psychological flexibility and has shown efficacy in treating a variety of psychiatric disorders, including depression, anxiety, and PTSD, with a meta-analysis revealing an average effect size of 0.66 at post-treatment across 704 participants.

ACT not only improves mental health outcomes but also benefits other medical areas such as chronic pain management and smoking cessation, demonstrating its versatility and positive impact on quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acceptance and commitment therapy]. Ducasse, D., Fond, G.[2019]

A national training initiative for Acceptance and Commitment Therapy for depression (ACT-D) led to a significant increase in therapist competency, with 96% of therapists achieving competency by the end of training, up from only 21% at the start.

Patient outcomes improved markedly, with average depression scores (BDI-II) decreasing from 30 to 19, indicating effective treatment, alongside increased quality of life scores and stronger therapeutic alliances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Training in and implementation of Acceptance and Commitment Therapy for depression in the Veterans Health Administration: therapist and patient outcomes. Walser, RD., Karlin, BE., Trockel, M., et al.[2022]

Acceptance and Commitment Therapy (ACT) is an effective treatment for Major Depressive Disorder (MDD), utilizing mindfulness and acceptance strategies to enhance psychological flexibility, which is crucial for behavior change.

ACT can be delivered in various formats, including individual, group, or self-help options, and has shown empirical support for its efficacy in improving depression outcomes through its core processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acceptance and Commitment Therapy for Major Depressive Disorder: Insights into a New Generation of Face-to-Face Treatment and Digital Self-Help Approaches. Apolinário-Hagen, J., Drüge, M., Hennemann, S., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Mental health facilities with ketamine infusion therapy in the United States in 2020: Co-location of dual diagnosis mental health and substance use disorder treatment. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Toward Synergies of Ketamine and Psychotherapy. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Cohort-Based Case Report: The Impact of Ketamine-Assisted Therapy Embedded in a Community of Practice Framework for Healthcare Providers With PTSD and Depression. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Single-dose intravenous ketamine or intramuscular naltrexone for high-utilization inpatients with alcohol use disorder: pilot trial feasibility and readmission rates. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Active mechanisms of ketamine-assisted psychotherapy: A systematic review. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ketamine psychedelic therapy (KPT): a review of the results of ten years of research. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Adjunctive Ketamine With Relapse Prevention-Based Psychological Therapy in the Treatment of Alcohol Use Disorder. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions. [2019]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Outcomes of Acceptance and Commitment Therapy for depression and predictors of treatment response in Veterans Health Administration patients. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Acceptance and Commitment Therapy in the Treatment of Alcohol Use Disorder and Comorbid Affective Disorder: A Pilot Matched Control Trial. [2018]

11. France pubmed.ncbi.nlm.nih.gov

[Acceptance and commitment therapy]. [2019]

12. England pubmed.ncbi.nlm.nih.gov

Training in and implementation of Acceptance and Commitment Therapy for depression in the Veterans Health Administration: therapist and patient outcomes. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Acceptance and Commitment Therapy for Major Depressive Disorder: Insights into a New Generation of Face-to-Face Treatment and Digital Self-Help Approaches. [2021]