A systematic review by the Canadian Network for Mood and Anxiety Treatments evaluated evidence for racemic ketamine in treatment-resistant depression. Single intravenous infusions have Level 1 evidence for efficacy in adults, while multiple or maintenance infusions have only Level 3 evidence. Adverse events include dissociative symptoms and hypertension. Non-IV formulations have Level 3 or 4 evidence. Single-dose IV racemic ketamine is a third-line recommendation; repeated use requires careful case-by-case risk-benefit assessment. Oral and other formulations should be limited to specialists with ketamine expertise at tertiary centers due to limited evidence and risk of misuse.
Both intravenous ketamine and intranasal esketamine significantly reduce depressive symptoms and suicidal ideation in people with treatment-resistant major depressive disorder. In a multi-site observational study of 53 patients, those receiving IV ketamine (26 patients, average age 52.8) and those receiving IN esketamine (27 patients, average age 43.9) showed similar improvements in depression severity and suicidal thoughts. Side effects were mild and temporary, with no significant difference in risk between the two treatments. The findings suggest both therapies are effective and well tolerated for treatment-resistant depression.
Intranasal esketamine, used for treatment-resistant depression, does not appear to carry significant abuse liability during an acute course of treatment. In a secondary analysis of a multicenter observational study, 23 patients with major depressive disorder reported neutral liking and no cravings for esketamine after their first dosing session, and these measures did not increase over eight sessions. Neither age, sex, baseline depression severity, side effects, nor study site influenced liking or cravings. The findings align with existing literature suggesting that acute esketamine treatment is not associated with high drug liking or cravings, though larger studies are needed.