Bipolar Depression, Treatment Resistant Bipolar Depression
Conditions
Keywords
ketamine, bipolar depression, bipolar disorder, bipolar
Brief summary
This is a prospective open-label observational study of patients with treatment resistant bipolar depression referred for intravenous ketamine, with an interventional component of fMRI.
Detailed description
This is a prospective open-label observational study of patients with treatment resistant bipolar depression referred for intravenous ketamine. All participants will receive an acute series of ketamine consisting of twice weekly infusions over three weeks. Non-responders will have their End of Study visits within 5 days of the last ketamine infusion. Responders (participants who achieve a greater than or equal to 50% decrease on their QIDS-SR-16 score from Baseline) will return for three weeks of continuation treatment (weekly ketamine) and then have their End of Study visit within 5 days of the last continuation treatment. All participants will undergo fMRI the prior to their first ketamine infusion, and after completion of their acute series.
Interventions
DRUGKetamine
Open-label Ketamine
OTHERFunctional magnetic resonance imaging (fMRI)
Functional magnetic resonance imaging (fMRI) of the brain
Sponsors
Brian Barnett
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a prospective open-label observational study of patients with treatment resistant bipolar depression referred for intravenous ketamine, with an interventional component of fMRI. All participants will receive an acute series of ketamine consisting of twice weekly infusions over three weeks. Non-responders will have their End of Study visits within 5 days of the last ketamine infusion. Responders (participants who achieve a ≥ 50% decrease on their QIDS-SR-16 score from Baseline) will return for three weeks of continuation treatment (weekly ketamine) and then have their End of Study visit within 5 days of the last continuation treatment. All participants will undergo fMRI prior to their first ketamine infusion and after completion of their acute series.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Written informed consent before any study related procedures are performed 2. Males/females at least 18 years of age but no older than 75 years of age 3. Meet DSM-5 criteria for a current Major Depressive Episode and lifetime Bipolar I disorder or Bipolar II disorder as determined by both: A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2) 4. A current depressive episode that has lasted a minimum of 4 weeks as determined by both: A. a clinician's diagnostic evaluation and B. confirmed with the MINI International Neuropsychiatric Interview (MINI 7.0.2) 5. Meet all the following criteria on symptom rating scales at screening: A. Montgomery Asberg Depression Rating Scale (MADRS) score ≥20 B. Young Mania Rating Scale (YMRS) score of ≤ 5 C. QIDS-SR-16 score of ≥ 11 6. Have had ≥ 2 adequate trials of mood stabilizers, antipsychotics (only those FDA approved for bipolar depression), or antidepressants or augmentation strategies during their lifetime. An adequate trial is defined as 4 weeks of medication at the minimum FDA approved dose. 7. In the opinion of the investigator, the patient is willing and able to comply with scheduled visits, treatment plan, and other trial procedures for the duration of the study.
Exclusion criteria
1. Meet DSM-5 criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, mental retardation, or pervasive developmental disorder 2. Meets any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Acute Response Changes in Subgenual Cingulate Functional Connectivity | Three weeks after treatment initiation | Seed-to-whole brain functional connectivity z-maps will be calculated from the left and right subgenual cingulate on the baseline and post-acute resting-state functional MRI (rs-fMRI) from each participant. After acute treatment, participants will be categorized as responders (≥50% decrease from baseline score of Quick Inventory of Depressive Symptomatology 16-item self-report, QIDS-SR-16) or non-responders. Brain regions in responders that exhibit significantly different treatment-related change in functional connectivity compared to non-responders will be identified using general linear model methods. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Acute Response Baseline Structural Connectivity | Three weeks after treatment initiation | Baseline structural connectivity will be assessed from baseline diffusion tensor imaging for each participant. White matter tracts in responders that exhibit significantly different mean transverse diffusivity compared to non-responders will be identified. |
| Sustained Response Changes in Subgenual Cingulate Functional Connectivity | Six weeks after treatment initiation | Acute responders will undergo a maintenance treatment phase (3 treatments over 3 weeks). After maintenance treatment, participants will be categorized as sustained responders (≥50% decrease from baseline QIDS-SR-16 score) or relapsers at the end of treatment. Brain regions in sustained responders that exhibit significantly different treatment-related change in subgenual cingulate brain functional connectivity maps compared to relapsers will be identified using general linear model methods. |
| Suicidal Ideation Changes in Subgenual Cingulate Functional Connectivity | Six weeks after treatment initiation | Brain regions in participants that experience suicidal ideation during treatment that exhibit significantly different treatment-related change in subgenual cingulate brain functional connectivity maps compared to participants who do not experience suicidal ideation will be identified using general linear model methods. |
Countries
United States
Outcome results
None listed