In patients suffering from treatment-resistant bipolar depression (BP) and with unresponsive chronic pain that is diagnosed as Complex Regional Pain Syndrome (CRPS)have responded to treatment with ketamine. The CRPS patients were treated with a five-day infusion of the drug produced pain relief in 75% of the patients and 67% of the BP responded after a single dose. Our studies indicates that the therapeutic activity of ketamine is due, in part, to (2R,6R)-hydroxynorketamine and dehydronorketamine and the pharmacological activities of the compounds have been investigated. In addition, metabolomic studies have determined that response and non-response to treatment with ketamine in BP patients is related to mitochodrial function and proteomic studies have also been recently carried out. This relationship is under investigation.