Oral ketamine for treatment resistant major depression – A double blind randomized controlled trial

Abstract

Background Major depression is a devastating common disorder. Current pharmacotherapy centers on noradrenergic and serotonergic modulation, but effect may require up to 21. Moreover, over a third of patients remain poorly unresponsive, termed Treatment Resistant Depression (TRD). Recently, intravenous ketamine has been shown to provide rapid amelioration of TRD, but patients were followed-up for extremely short times. We aimed to assess the clinical efficacy and safety of a three-week course of oral ketamine in outpatients with TRD. Methods In a double blind, randomized, placebo-controlled trial and 22 TRD patients received either oral ketamine or placebo as outpatients for 21 days. Patients were evaluated at pre-trial, 230minutes after drug administration, and at 21 days. The main outcome measure was the change in Montgomry Asberg Depression Rating Scale (MADRS) score. Result Twelve subjects were randomized to the ketamine group, and 10 to the placebo group. Four patients from the placebo group opted out due to treatment ineffectiveness. A repeated measures ANOVA showed a significant effect of time ( F (1,16)=15.12, P =0.001) together with a significant interaction between group an time ( F (1,16)=7.58, P =0.014). Tukey Honest significant difference (HSD) post hoc comparisons revealed a significant reduction in depression after 21 days in the ketamine group only ( P =0.0003). Conclusion In this study, oral ketamine in a sub-anesthetic dose caused a rapid amelioration of depressive symptoms in ambulatory TRD patients, and was well tolerated. The results of this study suggest that oral ketamine may hold significant promise in the care of outpatients with treatment resistant major depression.