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Add-on oral ketamine shows promise in treatment-resistant depression

Repeated oral ketamine produced rapid and persistent improvement of depressive symptoms in a small sample of outpatients with treatment-resistant depression who continued their usual treatment, according to a proof-of-concept study published in The British Journal of Psychiatry.

The results also showed that repeated oral ketamine was well tolerated among these participants in a community setting.

“Intravenous ketamine ... has been demonstrated to act as a novel antidepressant, with an extended effect following repeated infusions while maintaining a good safety profile,” Yoav Domany, MD, from Tel Aviv Sourasky Medical Center and Sackler School of Medicine, and postdoctoral research fellow, department of psychiatry and behavioral neuroscience, University of Cincinnati, and colleagues wrote. “However, intravenous administration presents major obstacles to clinical applicability, especially in community setting.”

Though previous study has examined IV and intranasal ketamine for treatment-resistant depression, research on oral ketamine is lacking. Therefore, the investigators conducted a randomized, placebo-controlled, proof-of-concept trial to determine the efficacy, safety and feasibility of add-on repeated oral ketamine for outpatients with treatment-resistant depression.

The researchers randomly allocated 41 participants to receive either 1 mg/kg oral ketamine or placebo three times a week for 21 days. All participants were instructed to continue taking their usual prescribed care. Patients were assessed at baseline, 40 minutes and 240 minutes after administration and on days 3, 7, 14 and 21 to measure change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores.

Of 22 participants who received treatment with ketamine and 19 who received placebo (control group), 33 patients completed the study. Among those receiving ketamine, Domany and colleagues observed a reduction in depressive symptoms between baseline and all other time points (P < .005), including day 21. In the control group, there was also a decrease in symptoms, but only at 40 minutes after initial administration (P < .05).

At the endpoint (day 21), the reduction in MADRS score was 12.75 among those receiving ketamine compared with 2.49 points among those receiving placebo (P < .001). The researchers reported that 27.3% of the ketamine group (n = 6) achieved remission as opposed to none in the control group (P < .05) at day 21.

Adverse effects were mild and transient, according to the safety analysis. Common adverse effects included increased systolic blood pressure, euphoria, dizziness and drowsiness after initial administration, all of which resolved within 1 hour. Follow-up safety evaluation at day 28 showed a maintained effect on MADRS scores in the ketamine group.

“Our results, although promising, cannot yet be applied to clinical practice without larger, randomized studies,” Domany and colleagues wrote. “Such studies are needed to address questions such as optimal dosing regimens, patient selection and treatment duration to properly assess the safety of long-term ketamine usage, the risk of misuse and the restricted means appropriate for at-home prescription.” – by Savannah Demko

Disclosure: The authors report no relevant financial disclosures.