Behavioural Activation Therapy and Esketamine for Resistant Depression

NCT06431386 | Terminated

• 1 other identifier: REB 2024002
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized clinical trial to test the effectiveness of combining a proven psychological intervention called behavioural activation therapy alongside esketamine treatment for treatment resistant major depressive episodes in individuals with major depressive disorder or bipolar disorder. Encouraging participants to practice new behaviours while their mood is improved through esketamine treatment may lead to more lasting recovery from depression.

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Bipolar Disorder

Keywords

Major Depressive Disorder; Esketamine; Psychotherapy; Behavioural Activation; Bipolar Depression

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptoms

  Change in Montgomery-Åsberg Depression Rating Scale (MADRS) score

  Baseline to the end of the induction phase (week 4); additional efficacy assessment time points will include end of weeks 2, 8 and 12

Secondary Outcomes (2)

• Speed of therapeutic effects

  Induction phase (weeks 1-4)

• Change in participant perceived functioning

  Baseline to end of induction phase (week 4), and the end of weeks 8 and 12

Study Arms (2)

Esketamine + Behavioural Activation Therapy

EXPERIMENTAL

Participants randomized to this arm will be administered esketamine treatment as per standard clinical care in conjunction with behavioural activation (BA) therapy. Both treatments will be initiated in Week 1 of the induction phase (first 4 weeks of esketamine treatment).

Behavioral: Behavioural Activation (BA) Therapy; Drug: Esketamine

Esketamine Alone

ACTIVE COMPARATOR

Participants randomized to this arm will be administered esketamine treatment as per standard clinical care and will be offered a course of BA therapy (12 one hour sessions) after their completion of the trial.

Drug: Esketamine

Interventions

Behavioural Activation (BA) Therapy BEHAVIORAL

Participants will receive weekly one-hour BA sessions on a day they are not receiving esketamine, delivered virtually or in person as per participant preference. The aim is for participants to learn to observe the relationship between what they did, felt, and thought and what was happening around them, and to identify conditions which maintained, increased, or weakened maladaptive behaviours. Functional behaviour analysis will be used in problem and behaviour evaluation and in planning and reviewing changes introduced by participants between sessions. Other techniques include self-observation and self-report, elaboration of activity hierarchies, behaviour programming, rehearsal and behavioural modelling, and contingency management. Between-session homework will develop relevant and rewarding routines to offer reinforcement in each participant's environment. Participants will be offered 12 BA sessions in total.

Esketamine + Behavioural Activation Therapy

Esketamine DRUG

Participants will receive intranasal esketamine twice weekly during the induction phase (first 4 weeks of treatment). Maintenance treatments are administered once per week or once every two weeks at the discretion of the treating physician for 8 additional weeks, totaling 12 weeks of esketamine treatment. Dosing for esketamine usually starts at 56mg on Day 1, followed by 56 or 84mg doses for subsequent treatments.

Esketamine + Behavioural Activation Therapy; Esketamine Alone

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• The Royal's Institute of Mental Health Research: lead

Study Sites (1)

The Royal Ottawa Mental Health Centre

Ottawa, Ontario, K1Z 7K4, Canada

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major; Bipolar Disorder

Interventions

Therapeutics; Esketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Study Officials

• Jeanne Talbot, MD PhD FRCP

  The Royal's Institute of Mental Health Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Clinical outcome assessments will be performed by raters blind to treatment allocation and not the treating therapist or physician. Ratings will be acquired prior to treatment administration.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician Scientist

Model Details: This pilot study is a single-site, parallel-arm, randomized clinical trial.

Study Record Dates

• First Submitted: May 22, 2024
• First Posted: May 28, 2024
• Study Start: June 11, 2024
• Primary Completion: September 17, 2025
• Study Completion: September 17, 2025
• Last Updated: October 1, 2025

Record last verified: 2025-09

Locations

CA (1)