Ketamine, an anesthetic and NMDA receptor antagonist, is used to treat chronic pain and depression, conditions that often co-occur and may share neural pathways. Intravenous and intranasal ketamine are both effective for acute depressive episodes, with intravenous administration having higher bioavailability and providing better post-operative pain relief while reducing opioid use. Few studies have addressed ketamine's effects on concurrent depression and pain. Larger randomized controlled trials are needed to compare the safety and efficacy of intravenous versus intranasal ketamine, identify ideal target populations, and determine optimal dosing for treating both conditions.
A single 96-hour infusion of ketamine, co-administered with clonidine, is well tolerated and produces a rapid and sustained antidepressant response in over 50% of adults with treatment-resistant depression. In an open-label study of 23 adults, depressive symptoms dropped markedly from an average MADRS score of 29 at baseline to 9 one day after infusion, and remained reduced at 2 weeks (13) and 8 weeks (15). Brain imaging showed that the infusion normalized overconnectivity in the limbic system and between the subgenual anterior cingulate cortex and the default mode network, with response-dependent and treatment-dependent connectivity changes.