Augmentation of response and remission to serial intravenous subanesthetic ketamine in treatment resistant depression

Background Ketamine has been showing high efficacy and rapid antidepressant effect. However, studies of ketamine infusion wash subjects out from prior antidepressants, which may be impractical in routine practice. In this study, we determined antidepressant response and remission to six consecutive ketamine infusions while maintaining stable doses of antidepressant regimen. We also examined the trajectory of response and remission, and the time to relapse among responders. Methods TRD subjects had at least 2-month period of stable dose of antidepressants. Subjects completed six IV infusions of 0.5 mg/kg ketamine over 40 min on a Monday-Wednesday-Friday schedule during a 12-day period participants meeting response criteria were monitored for relapse for 4 weeks. Results Fourteen subjects were enrolled. Out of twelve subjects who completed all six infusions, eleven (91.6%) achieved response criterion while eight (66.6%) remitted. After the first infusion, only three and one out of twelve subjects responded and remitted, respectively. Four achieved response and six remitted after 3 or more infusions. Five out of eleven subjects remain in response status throughout the 4 weeks of follow-up. The mean time for six subjects who relapsed was 16 days. Limitations Small sample and lack of a placebo group limits the interpretation of efficacy. Conclusions Safety and efficacy of repeated ketamine infusions were attained without medication-free state in patients with TRD. Repeated infusions achieved superior antidepressant outcomes as compared to a single infusion with different trajectories of response and remission. Future studies are needed to elucidate neural circuits involved in treatment response to ketamine.