The Impact of AMPA Receptor Blockade on Ketamine’s Anti-Suicidal Effects

Description

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 depression inventory used extensively to test Ketamine treatment effectiveness.
3. Exploratory: Perampanel pre-treatment reduces the anti-suicidal effect of Ketamine directly as well as indirectly through depression symptom remission.

Eligibility will be determined by psychiatric interview, rating scales and questionnaires, and a complete physical exam with electrocardiogram and labs. Individuals found eligible will receive perampanel or placebo, in counterbalanced order, 2.5 hours before a standard, subanesthetic Ketamine infusion (0.5 mg/kg over 40 minutes). Ketamine infusions will be at least three weeks apart and individuals will complete follow-up assessments through interview and electronic diary.