The study is a randomised, double-blind, crossover design with two treatment conditions: oral placebo or oral naltrexone preceding ketamine infusion during neuroimaging in subjects with treatment-resistant depression.~Each subject will participate in two imaging sessions on two separate days. Each subject will receive a dose of ketamine (IV infusion, 0.5 mg/kg over 40 minutes) during each scan. Subjects will receive either oral placebo or naltrexone 50 mg, 45 minutes before the initiation of each of the ketamine infusions.
The overarching aim of this research is to determine the acute effects of ketamine on brain glutamate, functional connectivity and cerebral blood flow in treatment-resistant depression, explore whether the effects are attenuated by the opioid receptor antagonist naltrexone and relate these findings to antidepressant response.