Single dosage of ketamine as a response predictor to a 21 days oral ketamine treatment. A two-phases control trial.

Background: Treatment response for ketamine, a rapid acting antidepressant, might be restricted to a portion of patients.

Hypothesis: Ketamine’s rapid therapeutic response to the first administration, can predict treatment remission on a 21 days of oral ketamine trial

Methods: We used a two-phase trial (Fig. 1); In phase 1, a randomized, double blind, placebo controlled phase, 40 treatment resistant depressed subjects, were randomized to thrice weekly oral ketamine treatment 1mg/kg or placebo for 21 days. In phase 2, the previously placebo-receiving subjects, received open label ketamine 1mg/kgx3/week for 21 days. Subject were evaluated pre-trial, after 4 hours and on days 3, 7, 14, and 21 as well as safety assessment on day 28. In order to predict remission at day 21 discriminant analyses were performed using MADRS after 4 hours of ketamine administration as a predictor.

Result: In phase 1, 22 subjects were randomized to the ketamine group, and 18 to the placebo group. In phase 2, 11 subjects received open label ketamine. For phase 1: the reduction in MADRS at day 21 was 12.09 points in the ketamine group, versus 1.50 in the placebo group (p=0.05) (Fig. 2), and six subjects (27.3%) achieved remission. In phase 2, the reduction was 14.33 points, and one subject (9%) achieved remission. No serious adverse events were documented. Based on the response to the first dosage of ketamine (phases 1&2- ketamine receiving only), we correctly categorized 90.9% of all subjects. (100% out of 26 non-remising, and 57.1% out of 7 remising) (Wilks’ Lambda= 0.72, chi(1)=10.03, p=.002). (Fig. 3)

Conclusion: Repeated administration of oral ketamine produced rapid and sustained amelioration of depressive symptoms, and was well tolerated. Based on the response to the first dose of ketamine, we managed to predict achievement of remission in 90.8%. Notably, all the patients (100%), who did not respond to the first dosage, did not eventually achieve remission. Our results suggests that once a patient did not respond to the first ketamine administration, further administrations may be futile.