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Intravenous (IV) ketamine and even the newly approved esketamine nasal spray as options for treatment-resistant depression are costly and difficult to implement, prompting interest in oral ketamine, despite its poor 20% bioavailability. These investigators reviewed evidence on oral ketamine in depressed patients from two small randomized, controlled trials (RCTs; 68 patients receiving ketamine; 1 RCT of depressed patients with chronic headache) and several uncontrolled studies (1 prospective study of depressed hospice patients, n=14; 10 case reports or series or chart reviews, n=141).
Few patients had treatment-resistant disease, effects were uniformly delayed by 2 to 6 weeks, and the one RCT evaluating remission found only a difference in r…