Mechanism of Action Underlying Ketamine’s Antidepressant Effects: The AMPA Throughput Theory in Patients With Treatment-Resistant Major Depression
Randomised, triple-blind, placebo-controlled add-on study (n=70) testing whether oral perampanel (8 mg) blocks the antidepressant effects of intravenous ketamine (0.5 mg/kg) in adults with treatment-resistant major depressive disorder.
Details
Ketamine produces rapid antidepressant effects; this study tests whether AMPA receptor throughput is necessary for those effects by pre-treating patients with the AMPAR antagonist perampanel versus placebo and measuring clinical and electrophysiological outcomes.
Phase I entails medication taper and baseline imaging/physiology; Phase II randomises participants to blinded perampanel or placebo with an open-label ketamine infusion (0.5 mg/kg IV) and repeated sEEG, TMS and MEG and clinical ratings (MADRS) to assess antidepressant response and neurophysiological biomarkers.