Precision Medicine and Target-Controlled Infusions Significantly Improves the Efficacy of Ketamine Therapy for Treatment-Resistant Depression

Objective: Ketamine has shown promise as a rapidly acting antidepressant, but real-world effectiveness rates are lower than those reported in clinical trials. To bridge this gap, we developed a novel methodology utilizing Precision Medicine and Target-Controlled Infusions to enhance the effectiveness and durability of ketamine infusion therapy. Methods: 87 patients with treatment-resistant depression (TRD) underwent a three-step Precision Medicine evaluation protocol before receiving ketamine therapy. The dose of ketamine was determined for each subject using pharmacokinetic modeling to achieve optimal target-controlled plasma concentrations via intravenous infusion over 30 minutes. After the induction phase, patients received two additional infusions within 3-6 months before entering the maintenance phase. Symptom severity was measured using the Beck Depression Index-II (BDI-II). Results: 78 of 87 (89.4%) patients completed the induction phase, of whom 88.4% responded, and 56.3% achieved remission by the fifth infusion. These results compare favorably to response rates of 18.3-45.5% and remission rates of 27.3% reported in other studies. Notably, the average time between protocol completion and the need for maintenance infusion was 245 days, compared to 26 days with standard ketamine infusion. Conclusions: Precision Medicine and Target-Controlled Infusions represent a clinically applicable approach to ketamine infusion therapy that significantly improves ketamine therapy effectiveness in multiple domains. Compared to the standard ketamine infusion protocol, this novel methodology results in a three-fold increase in response rates, a two-fold increase in remission rates, and a nine-fold increase in response durability.