A New Methodological Approach to Improve the "Real Word" Effectiveness of Ketamine Infusion Therapy for Treatment-Resistant Depression

Abstract: Objective: Ketamine is recognized as a rapidly acting antidepressant; however, discrepancies exist between the "Efficacy" reported in research studies (70-85%) versus significantly lower "Effectiveness" (18.3-45.5%) reported in community-based settings. To offset the "Efficacy-Effectiveness" gap a novel, clinically applicable methodology (RESTORE) was developed to improve both effectiveness and durability. Here we report the results of a 60-month, retrospective study of 87 patients who received RESTORE for TRD and compare outcomes to community based-studies utilizing the "standard" ketamine infusion. Methods: Patient eligibility was determined by a three-step patient evaluation and suitability protocol. Patients received 3 infusions over 3 days and were dosed with the amount of ketamine, based on pharmacokinetic modeling, to achieve optimal blood concentrations. The medication was administered intravenously via a multimodal, variable rate infusion over 30 minutes. Following induction, patients received two additional infusions within 3-6 months before entering the maintenance phase. Symptom severity was determined utilizing the Beck Depression Index-II (BDI-II). Results: 78 of 87 (89.4%) patients completed the 2-phase infusion protocol, of which 88.4% responded and 56.3% remitted by the fifth infusion. This compares favorably to the 18.3-45.5% response and 27.3% remission rate reported in other studies. Most notably, the average period between protocol completion and the need for maintenance infusion was 245 days compared to 26 days with ketamine infusion. Conclusions: The novel RESTORE infusion protocol represents a clinically applicable methodological approach to ketamine infusion therapy that results in significantly improved effectiveness by 3-fold and response durability by 9-fold compared to the standard ketamine infusion.Short Description: The study provides compelling evidence that the RESTORE infusion protocol significantly improves ketamine therapy effectiveness by 3-fold and durability by 9-fold when compared to the standard ketamine infusion. This novel, methodological approach to ketamine infusion therapy overcomes barriers to ketamine therapy including the number of infusions needed, patient convenience issues, and overall treatment expense. RESTORE represents the next generation in ketamine therapy that may be a more effective approach to ketamine therapy for treatment-resistant depressionName of Sponsoring Organization(s): Ketamine Research Institute