Combining Behavioural Activation Therapy with Esketamine for Resistant Depression

Optimizing the Synergy Between Behavioural Activation Therapy and Esketamine for Resistant Depression

Not applicable Interventional The Royal's Institute of Mental Health Research · NCT06431386

This study is testing if combining a therapy that encourages positive activities with esketamine can help people with hard-to-treat depression or bipolar disorder feel better.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment40 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorThe Royal's Institute of Mental Health Research Academic / other
Locations1 site (Ottawa, Ontario)
Trial IDNCT06431386 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining behavioural activation therapy with esketamine treatment for individuals suffering from treatment-resistant major depressive disorder or bipolar disorder. The approach aims to enhance mood through esketamine while encouraging participants to engage in new behaviors that may lead to lasting recovery. The study targets individuals who have not responded adequately to traditional antidepressant medications, addressing a significant gap in current treatment options for severe depressive episodes.

Who should consider this trial

Good fit: Ideal candidates are English-speaking adults aged 18-65 with major depressive disorder or bipolar disorder who have not responded to at least two different antidepressant treatments.

Not a fit: Patients with depression secondary to severe medical illnesses, active psychotic symptoms, or a recent history of substance use may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective treatment option for patients with treatment-resistant depression, potentially leading to improved long-term outcomes.

How similar studies have performed: Other studies have shown promising results with ketamine and psychotherapy combinations, indicating potential for success in this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* English speaking
* Ages 18-65
* Participants meeting criteria for major depressive disorder (MDD) or bipolar disorder, depressive episode without psychotic symptoms according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-5).
* Participants who have not responded adequately to at least two separate courses of treatment with different antidepressants, each of adequate dose and duration, in the current moderate to severe depressive episode.

Exclusion Criteria:

* Depression secondary to a stroke, cancer, or other severe medical illnesses.
* Pregnant, lactating or of childbearing potential and unwilling to use an approved method of contraception during the study.
* A history of intracerebral hemorrhage, vascular disease.
* Active psychotic symptoms.
* Current and/or recent history (\<12 months) of substance use/dependence (except for caffeine or nicotine) or problematic current alcohol use or dependence as defined by DSM-5 criteria.
* A diagnosis of major neurocognitive disorder or a Montreal Cognitive Assessment (MOCA) score \<24.
* Active suicidal intent with the absence of psychotic symptoms is not an exclusion criterion, as this is not atypical in individuals with treatment-resistant, and/or severe depression (safety monitoring will be carried out by research personnel/study psychiatrists).
* Known history of intolerance or hypersensitivity to ketamine.
* Any other condition that, in the opinion of the PI/study investigator(s), would adversely affect the participant's ability to complete the study or its measures.
* The participant must not be receiving psychotherapy treatment outside the clinical trial for the duration of the study.

Where this trial is running

Ottawa, Ontario

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Depressive Disorder, Treatment-ResistantDepressive Disorder, MajorBipolar DisorderMajor Depressive DisorderEsketaminePsychotherapyBehavioural ActivationBipolar Depression
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.