Yale University
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).
The investigators will use the NMDAR antagonist Ketamine combined with the AMPAR antagonist perampanel to test the following hypotheses: Primary Hypotheses: 1. Perampanel pre-treatment will attenuate Ketamine's reduction of suicidal ideation as assessed 24 hours after drug infusion with a well-established suicidal ideation inventory that has been shown to be sensitive to Ketamine's anti-suicidal effects. 2. Perampanel pre-treatment will attenuate the antidepressant response to Ketamine as assessed 24 hours after drug infusion with the Hamilton Depression Inventory, a well-established depress…
Inclusion Criteria: * 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 SC…
Perampanel will be administered 2.5 hours before Ketamine infusion
Ketamine infusion (0.5 mg/kg infusion over 40 minutes) will be administered 2.5 hours post perampanel or placebo administration.
Placebo will be administered 2.5 hours before Ketamine infusion
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