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How ketamine produces rapid antidepressant actions remains unclear, but they have often been attributed to ketamine's antagonism of N-methyl-D-aspartate receptors. Ketamine also acts on other neurotransmitters, with its antinociceptive effects attributed to actions on mu and delta opiate receptors. Hypothesizing that ketamine's antidepressant actions are related to opiate systems, investigators conducted a double-blind crossover study involving 14 patients with nonpsychotic, nonatypical severe depression due to major depressive disorder or bipolar II disorder (mean age, 41; mean illness duration, 24 years; current episode, 9 years).
Patients received the opiate receptor antagonist naltrexone (50 mg) or placebo and were then infused with suba…