A PILOT STUDY: AN OPEN-LABEL BIOMARKER DEVELOPMENT OF KETAMINE FOR UNIPOLAR REFRACTORY DEPRESSION

Abstract

Objective: The primary objective of this study is to evaluate the antidepressant efficacy of an acute intravenous subanesthetic ketamine treatment (0.5 mg/kg) for patients with unipolar treatment-resistant depression (TRD). The secondary objective of this study is to identify peripheral blood-based biomarkers associated with response to treatment. Method: Fifteen adults diagnosed with TRD completed an open-label study of repeated infusions of low dose ketamine (0.5 mg/kg) over the course of four weeks. Blood was collected from eleven patients at three time points throughout the acute treatment to analyze peripheral biomarkers including irisin, IL-6, IL-10, TNF-α, and BDNF. Results: Repeated ketamine infusions produced a significant decrease in total average MADRS scores in fifteen patients with unipolar TRD [F(1, 14) = 49.06, p<0.01] at all timepoints. Improvements in depressive symptoms were significant at one-week [t(14)=9.32, p<0.01], and continued to significantly decrease until two-weeks [t(14)=2.27, p<0.05]. The antidepressant effect was maintained for the entire duration of treatment. Psychiatric symptoms measured by the BPRS significantly decreased throughout treatment, which correlated to the decrease in MADRS scores (r=0.99, p<0.01). Ketamine was generally well-tolerated, and we observed improvements in functional impairment and anhedonia with no increases in manic symptoms. Levels of BDNF throughout treatment significantly correlated to decreases in MADRS scores (r=-0.66, p<0.05), and baseline BDNF levels predicted mood response at one- [F(1, 10) = 12.23, p<0.01] and four-weeks [F(1, 10) = 9.55, p<0.05]. Conclusion: Repeated subanesthetic doses of ketamine infusions significantly improve depressive symptoms and produce sustained antidepressant effects over four weeks of treatment. Ketamine may be an efficacious and safe pharmacological option for the acute treatment of patients suffering from severe treatment-resistant depression, and BDNF has the potential to function as a prognostic biomarker for predicting response to ketamine treatments.