Male and female patients diagnosed with MDD, ages 18 to 65 years, currently experiencing a major depressive episode, will be recruited for this study. The study will comprise the double-blind crossover administration of either diazoxide (200-400 mg/day given orally) or placebo. The study will assess the efficacy of three weeks of a glutamate transporter enhancer (diazoxide, 200-400 mg/day given orally) compared with placebo in improving overall depressive symptomatology in patients with treatment-resistant MDD. Other aims of the study include: 1) determining whether changes in brain neurochemicals (glutamate) correlate with antidepressant response (as measured by decreases in Montgomery-Asberg Depression Rating Scale (MADRS) total scores) in response to diazoxide in patients with treatment-resistant MDD; and 2) examining other potential biomarkers of response.