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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with both alcohol use disorder (AUD) and treatment-resistant depression (TRD). It combines ketamine, known for its rapid antidepressant effects, with Acceptance and Commitment Therapy (ACT), a talk therapy that aids in managing thoughts and emotions. The researchers aim to determine if this combination can more effectively reduce alcohol use and improve depressive symptoms. Suitable participants have depression unresponsive to standard medications and also face challenges with alcohol use. As an unphased trial, this study provides a unique opportunity for participants to contribute to groundbreaking research that could lead to innovative treatment options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Acceptance and Commitment Therapy (ACT) is generally easy for patients to handle. Studies have found that ACT can reduce substance use and improve mental health issues like depression. For instance, ACT has been linked to positive results in managing symptoms of substance use disorders, with participants showing significant decreases in substance use and distress.

ACT helps by encouraging people to accept their thoughts and feelings instead of fighting them, aiding in the management of both substance use and mental health problems. Studies have not reported any major safety concerns with ACT, making it a promising option for those facing alcohol use disorder and depression. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Acceptance and Commitment Therapy (ACT) for alcoholism and depression because it offers a fresh approach compared to traditional treatments like cognitive-behavioral therapy or medication. Unlike standard therapies that often focus on changing negative thoughts, ACT encourages individuals to accept their thoughts and feelings while committing to personal values and behavioral changes. This method can lead to more sustainable mental health improvements by enhancing psychological flexibility. It's a distinctive approach that might resonate better with some individuals, offering them a new pathway to recovery.

What evidence suggests that ACT + Ketamine might be an effective treatment for alcoholism and depression?

Research has shown that Acceptance and Commitment Therapy (ACT) effectively treats substance use problems, such as alcohol use disorder (AUD). Studies have found that ACT helps individuals reduce substance use and improve outcomes for those with depression. By assisting patients in managing their emotions and thoughts, ACT can lead to reduced drinking and decreased depression. In this trial, participants will receive ACT. Although other research explores the combination of ACT with ketamine, this trial specifically focuses on the effects of ACT alone. ^{1 2 3 6 7}

Who Is on the Research Team?

Nicolas Garel, MD MSc

Principal Investigator

Centre Hospitalier d'Université de Montréal

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S221214472400053X

Effectiveness of acceptance and commitment therapy for ... Three previous systematic reviews have concluded that ACT has a positive effect on treatment outcomes for substance use disorders. Specifically, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7524566/

The Use of Acceptance and Commitment Therapy in ... Most of the studies showed that ACT was effective in the management of SUD showing significant evidence of a reduction in substance use or total ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06620276

ACT_for Alcohol Use Disorder and Depression 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 ...

4. brieflands.com brieflands.com/articles/ijpbs-110135

Effectiveness of Acceptance and Commitment Therapy in ... The present research results showed that ACT was effective in reducing depression in people with substance use disorders in the experimental group. Subjects in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5039035/

Effectiveness of Web-Delivered Acceptance and ... ACT in a Web-based delivery format was found to be effective in the management of depression. Rates of adherence to study protocols and completion were high ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12249220/

The Role of Acceptance and Commitment Therapy in ... Findings suggest that ACT is an effective treatment for reducing distress and disability associated with psychotic symptoms. Effect size: The ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0005789415000477

Acceptance and Commitment Therapy in the Treatment of ... Patients in the ACT group reported significantly higher CAD at 3 and 6 months, significantly lower BDI and BAI scores at 3 and 6 months, and significantly lower ...