The purpose of this study is to test the hypothesis that the anti-depressant and anti-suicidal effects of the N-methyl-D-aspartate receptor (NMDAR) antagonist Ketamine is critically dependent on stimulation of Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid receptors (AMPAR).
Current depression as indicated by a score greater than 17 on the full Hamilton Depression Rating Scale (HDRS-17) AND current major depressive episode as determined by structured clinical interview (SCID-5)
Current suicidal ideation as indicated by a score ≥ 2 on the HDRS-17 Item #3 ("wishes to be dead (or any thoughts of possible death to self)")
Anti-depressant resistant depressive symptoms, defined by a history of failure of one or more adequate anti-depressant trials
Participants will meet DSM-5 Criteria for MDD, PTSD or Bipolar Disorder as determined by the SCID-5
A score on the Columbia-Suicide Severity Rating Scale [43] in the "intent" or "intent with plan" categories within the last 3 months or judged by Dr. Krystal or Dr. Driesen to be at serious risk for suicide.
Psychiatric hospitalization in the past two months
Suicide attempt in the past two months
More than half hour unconsciousness after trauma
Crossover
Perampanel 6 MG
DrugPerampanel will be administered 2.5 hours before Ketamine infusion
Ketamine
DrugKetamine infusion (0.5 mg/kg infusion over 40 minutes) will be administered 2.5 hours post perampanel or placebo administration.
Placebo
DrugPlacebo will be administered 2.5 hours before Ketamine infusion
Change in suicidal ideations in response to Ketamine
Change in suicidal ideation will be assessed 24 hours post-Ketamine infusion using a Scale for Suicidal Ideation, composed of the first five items of the Beck Suicide Inventory + the Hamilton Depression Rating Scale (HAMD-7) suicidality item. The first five items of the Beck Suicide Inventory are rated on a scale of 0-2, and the suicidality item on the HAMD-7 is rated from 0-4. Scores are totaled and will be analyzed as the dependent variable in a mixed-effects model with drug condition (placebo/perampanel) and time (baseline, 24-hour follow up) as within-subject factors.
Change in antidepressant response to Ketamine
Changes in depressive symptoms will be assessed 24 hours post-Ketamine infusion using the full Hamilton Depression Rating Scale (HAMD-7), a 7-item survey to assess depression. Scores range from 0-26 with scores indicating full remission (0-3) and partial/non-response (4-26). Scores are totaled and will be analyzed as the dependent variable in a mixed-effects model with drug condition (placebo/perampanel) and time (baseline, 24-hour follow up) as within-subject factors.
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Yale University
Lead sponsor
American Foundation for Suicide Prevention
Collaborator
National Center for PTSD
Collaborator
VA Connecticut Healthcare System
Collaborator
