None listed
Conditions
Brief summary
Our study will compare oral ketamine treatment with oral ketamine treatment and Behavioural Activation Therapy (BAT) for patients with treatment resistant depression. We will test the feasibility of providing oral ketamine and BAT over 8 weeks in a study. We hypothesise that adding BAT to oral ketamine treatment will prolong the response and delay relapse for three months after treatment ends. We also hypothesise that BAT and oral ketamine will be well tolerated by participants.
Interventions
Participants will be randomised to receive oral ketamine plus Behavioural Activation Therapy (BAT) (the intervention) or oral ketamine plus Treatment As Usual (TAU) (the comparator).
Ketamine will commence at a dose of 0.5mg/kg diluted with 50 ml orange juice and sipped over 30-60 minutes. Initial dosing will be twice weekly (with gaps of 3 and 4 days between doses). If tolerated and if the Montgomery Asperg Depression Rating Scale (MADRS)>6 on follow-up (indicating mild depression or greater)
Participants will be randomised to receive oral ketamine plus Behavioural Activation Therapy (BAT) (the intervention) or oral ketamine plus Treatment As Usual (TAU) (the comparator). Ketamine will commence at a dose of 0.5mg/kg diluted with 50 ml orange juice and sipped over 30-60 minutes. Initial dosing will be twice weekly (with gaps of 3 and 4 days between doses). If tolerated and if the Montgomery Asperg Depression Rating Scale (MADRS)>6 on follow-up (indicating mild depression or greater), dose can be increased to 1.5 mg/kg and then 2 mg/kg. If the MADRS is <6 on follow-up, dosing can be reduced to weekly intervals at participant request. Dosing will be individualised through discussion with nursing staff. All participants will receive nursing contact and oversight on Ketamine dosing days and by telephone as needed over the study period. BAT consists of 12 sessions provided at twice-weekly intervals for 4 weeks, then weekly intervals for 4 weeks. Sessions will be timed to occur within 24 hours of Ketamine treatments. BAT will be based on the manual by Lejuez et al. and be adapted by Assoc. Prof Jordan, Dr Katie Douglas, and Prof Greg Murray to work synergistically with the Ketamine treatment. BAT has already been adapted using He Puna Whakaata principles for use with Maori participants. BAT will provide an individual formulation for the participant and be a holistic treatment package alongside Ketamine therapy. BAT content includes psychoeducation about depression and the BAT model, values, goal setting, scheduling pleasant and mastery activities, negotiating support from others, dealing with rumination and worry, skills training as needed (e.g. problem solving, assertive communication) and managing early signs of relapse. BAT will include an initial focus on symptom reduction followed by maintenance of improvements and behavioural change to prevent relapse. BAT therapy session will be 40-50 minutes in duration and occur face-to-face unless specific circumstances such as sickness arise which mean a zoom session is desirable. BAT will be undertaken by nurses and psychologists trained in BAT and supervision of BAT therapists and fidelity checks of BAT delivery will occur.
Sponsors
University of Otago
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Participants aged between 18 and 65 years with treatment-resistant, DSM 5, Major Depressive Disorder (TR-MDD) are eligible for entry to the study. A standard definition for treatment resistance will be used: having trialled, and not responded to, at least two antidepressant medications at adequate doses for more than 6 weeks. At screening, patients will have a Hamilton Depression Rating Scale-17 (HAMD) greater than 16, reflecting depression of at least moderate severity. Participants will be required to be on stable medication treatment (or no treatment) for at least 1 month prior to screening for the study and commit to remaining on the same medication during active treatment to ensure treatment withdrawal or dose changes do not confound study effects. Proficient in spoken English
Exclusion criteria
Evidence of severe acute or chronic medical conditions (e.g. diabetes, ischaemic heart disease, chronic obstructive airways disease, cerebro-vascular disease); Past or current diagnoses of schizophrenia, bipolar disorder, or current psychotic symptoms; moderate-severe personality disorder; Current or recent significant suicidal ideation; Current or recent (past 6 months) substance use disorder; Prior history of seizures; susceptibility to photosensitivity; or a history of allergic skin reactions; prior history of serious head injury or other neurological condition resulting in ongoing cognitive impairment; Participants who are breast feeding or pregnant Receiving active psychotherapy for MDD (supportive psychotherapy can be placed on hold during the study) Having received a course of BAT in the last 12 months; previous non-response to BAT or Ketamine treatment Electro-Convulsive Therapy (ECT) in the last 6 months.
Outcome results
None listed