Auditory MMN EEG in TRD in Response to Ketamine

Study Overview
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Brief Summary
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To develop and test a neurocomputational model of ketamine treatment response predictions in TRD.

Detailed Description
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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.

Official Title
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Deciphering Metacognition and Treatment Response in Depression With a Novel Digital Paradigm

Conditions
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Treatment-resistant Depression (TRD)

Intervention / Treatment
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* Drug: Ketamine


Participation Criteria
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Eligibility Criteria
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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: History of bipolar disorder or psychosis Current substance use or history of substance use during the past year (excluding nicotine and caffeine use disorder) Concomitant major and unstable medical or neurologic illness or a history of seizures. Non-English-speaking individuals.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ketamine|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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical remission | 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 | 4 weeks following the baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modelling | Modelling the underlying cognitive and behavioural mechanisms to their neural causes from the effect of ketamine on TRD patients | 2 weeks following the baseline visit |