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Oral ketamine shows promising antidepressant effects

A systematic review published in Journal of Clinical Psychiatry concluded that the available evidence isn’t enough to support the use of oral ketamine for depression; however, two randomized controlled studies showed that oral ketamine has significant antidepressant effects and good tolerability.

“While IV ketamine is recognized as the gold standard route of administration, the use of IV infusions has poor feasibility, accessibility and scalability as infusions clinics are resource intensive with high costs and require patients to physically visit clinics for each treatment,” Joshua D. Rosenblat, MD, of the mood disorders psychopharmacology unit, University of Toronto, Canada, and colleagues wrote. “The large majority of antidepressants are orally administered, giving them the greatest potential for accessibility and scalability. Therefore, if effective and well tolerated, oral ketamine may be a preferred alternative to the IV route.”

Researchers searched clinical databases for relevant articles to analyze the antidepressant efficacy, safety, tolerability and dose range of oral/sublingual ketamine for bipolar and unipolar depression. They also examined anti-suicide effects, time to effect, and efficacy in treatment-resistant depression.

Rosenblat and colleagues identified 13 clinical studies that evaluated oral ketamine for depression, of which two were randomized controlled trials, one was a prospective open-label trial, five were retrospective chart reviews and five were case reports.

Although the two randomized controlled trials showed that oral ketamine had antidepressant efficacy with good tolerability and safety, the researchers found no significant changes in depressive symptom severity right away, only after 2 to 6 weeks of treatment (P < .05). According to the results, both randomized controlled trials were at high-risk for bias because of insufficient intent-to-treat analysis and monitoring of adverse events.

In the open-label trial, eight terminally ill participants who received oral ketamine experienced significant reductions in symptoms of depression at day 14 and anxiety at day 3, with these improvements remaining significant through day 28 (P < .01). However, the authors did not report an intent-to-treat analysis. The retrospective case series and care reports examining oral ketamine for depression (n = 141) yielded good tolerability and safety with no clinically significant adverse effects; antidepressant effects varied with response rates from 18% to about 80%. Only case report-level data had evidence of rapid antidepressant effects with oral ketamine for depression.

In addition, Rosenblat and colleagues found that dosages and frequency of oral ketamine administration varied (ie, 0.5 mg/kg to 7mg/kg; 3 times a day to once a month), though most studies provided dosages of 1 mg/kg to 2 mg/kg every 1 to 3 days. There was no evidence of reported clinically significant adverse effects, according to the results.

“While a limited number of studies showed promising results for antidepressant effects and good tolerability, further research is needed to more robustly evaluate oral ketamine prior to recommendation for clinical use,” the researchers wrote. “Future studies should focus on dose-response relationships, onset of action, anti-suicide effects and efficacy in [treatment-resistant depression] samples and should more rigorously evaluate safety and tolerability.” – by Savannah Demko

Disclosure: Rosenblat reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.