Clinical TrialTreatment-Resistant Depression (TRD)EsketamineEsketamineTerminated

Behavioural Activation Therapy and Esketamine for Resistant Depression

Randomised, parallel-arm trial (n=6 actual) comparing concurrent behavioural activation therapy plus intranasal esketamine versus esketamine alone for treatment-resistant depressive episodes in MDD or BD.

Target Enrollment
6 participants
Study Type
Phase NA interventional
Design
Randomized, single Blind

Detailed Description

This single-site, parallel-arm randomized clinical trial tests whether combining behavioural activation therapy with intranasal esketamine produces larger, faster, and more sustained reductions in depressive symptoms than esketamine alone.

Esketamine is administered intranasally with an induction phase (twice weekly for 4 weeks) followed by maintenance (once weekly or biweekly) for a total treatment period of 12 weeks; BA therapy consists of 12 weekly one-hour sessions delivered virtually or in person.

Primary outcomes assess depressive symptom change and speed of antidepressant response; secondary outcomes include functional recovery measures and treatment feasibility in a naturalistic academic-hospital setting.

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

cbt

Study Arms & Interventions

Esketamine + BA

experimental

Concurrent intranasal esketamine plus weekly behavioural activation therapy (BA) for 12 sessions.

Interventions

  • Compound
    via Other• weekly• 12 doses total

    Behavioural Activation (BA) therapy: 12 one-hour sessions, virtual or in person; delivered on a non-esketamine dosing day.

  • Esketamine56 - 84 mg
    via Other• twice weekly induction then weekly/biweekly maintenance

    Intranasal esketamine — induction twice weekly for 4 weeks (usually 56 mg Day 1 then 56 or 84 mg), maintenance up to week 12.

Esketamine alone

active comparator

Intranasal esketamine as treatment as usual; BA offered after week 12.

Interventions

  • Esketamine56 - 84 mg
    via Other• twice weekly induction then weekly/biweekly maintenance

    Intranasal esketamine per standard clinical care (induction then maintenance).

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • English speaking
  • Ages 18–65
  • Meet DSM-5 criteria for major depressive disorder (MDD) or bipolar disorder, depressive episode without psychotic features
  • Failure to respond adequately to at least two separate antidepressant trials of adequate dose and duration in the current moderate to severe depressive episode

Exclusion Criteria

  • Exclusion Criteria:
  • Depression secondary to stroke, cancer, or other severe medical illness
  • Pregnant, lactating, or of childbearing potential and unwilling to use approved contraception during the study
  • History of intracerebral haemorrhage or vascular disease
  • Active psychotic symptoms
  • Current or recent history (<12 months) of substance use disorder or problematic alcohol use (DSM-5 criteria), except caffeine or nicotine
  • Major neurocognitive disorder or MOCA score <24
  • Known intolerance or hypersensitivity to ketamine
  • Any condition that, in the opinion of the PI/investigator, would adversely affect ability to complete study or measures
  • Receiving outside psychotherapy during study participation

Study Details

Locations

The Royal Ottawa Mental Health Centre — Ottawa, Ontario, Canada

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