Treatment-resistant Depression (TRD)
Conditions
Brief summary
To develop and test a neurocomputational model of ketamine treatment response predictions in TRD.
Detailed description
The investigators propose applying a previously validated computational model of the MMN and the ensuing effects of NMDAR antagonism to predict treatment response following ketamine infusions in TRD patients and distinguish ketamine's antisuicidal effects from those related to mood improvements. The study has two subgoals: first, the computational mechanisms underlying MMN reductions that predict ketamine treatment response in TRD patients will be examined. Second, the computational mechanisms will be linked to their underlying neural causes using neural circuit models. Beyond understanding ketamine's short- and long-term mechanisms of action in TRD, the parameters obtained from fitting these models to noninvasive EEG recordings may facilitate single-patient treatment predictions. If successful, this approach may provide clinically useful prognostic statements in individual patients.
Interventions
DRUGKetamine
Participants suffering from TRD will receive their ketamine treatment intravenously twice weekly for two weeks (4 treatments in total). A dose of 0.5 mg/kg is infused over 40 minutes, with dose adjustments made at the psychiatrist's discretion.
Sponsors
Centre for Addiction and Mental Health
Toronto Metropolitan University
Unity Health Toronto
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Inclusion criteria
1.18 to 65 years of age 2. Meeting Diagnostic and Statistical Manual for Mental Disorders (DSM-5) criteria for MDD and in a Major Depressive Episode and ≥10 on the Montgomery-Asberg Depression Rating Scale (MADRS). 3\. Competent to consent-based on their ability to provide a spontaneous narrative description of the key elements of the study. 4\. Failure of at least two trials of antidepressant therapy during the current episode (treatment-resistant depression) and receiving ketamine treatment clinically as administered by their clinician 5. Staying on stable dosages of any concomitant psychotropic medications.
Exclusion criteria
1. History of bipolar disorder or psychosis 2. Current substance use or history of substance use during the past year (excluding nicotine and caffeine use disorder) 3. Concomitant major and unstable medical or neurologic illness or a history of seizures. 4. Non-English-speaking individuals.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission | 4 weeks following the baseline visit | Remission, defined as MADRS \<10, and suicide risk reduction is defined as a ≥ 50% reduction in the suicidal ideation item of the MADRS scale from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modelling | 2 weeks following the baseline visit | Modelling the underlying cognitive and behavioural mechanisms to their neural causes from the effect of ketamine on TRD patients |
Countries
Canada
Contacts
Primary ContactVenkat Bhat, MD MSc
Outcome results
None listed