A Higher Dose (0.8 mg/kg) of Ketamine Infusion for Treatment-resistant Depression: An Open-label Study in Taiwan

Objective: Studies of the Caucasian population showed that the treatment response rate of 0.5 mg/kg ketamine infusion is as high as 70% in patients with treatment-resistant depression (TRD). By contrast, our earlier study has found a response rate of about 50% in Taiwanese patients with TRD, with much lower blood levels of ketamine and norketamine. In the current study, we intended to investigate whether a higher (0.8 mg/kg) dose of ketamine infusion can improve the treatment outcome. Methods: An open-label study with six TRD patients was done. Every participant received a single dose (0.8 mg/kg) of ketamine infusion and was followed up for two weeks for depressive symptoms. The blood levels of ketamine and norketamine were also assessed. We combined the data from the current open-label study and our previous randomized double-blind study (0.5 mg/kg, 0.2 mg/kg, and placebo) for further analyses. Results: The treatment response rate in the 0.8 mg/kg group was 66.7% at 240 min after ketamine infusion, which is higher than that in the 0.5 mg/kg group. A generalized estimating equation model indicated a group effect (p < 0.001), a time effect (p < 0.001), and a group*time effect (p < 0.001) for the trajectory of the total depression score among four groups. Ketamine and norketamine levels were dose related (0.8 mg/kg > 0.5 mg/kg > 0.2 mg/kg). Adverse effects, such as a floating feeling and dizziness, did not differ in subjects between the 0.8 mg/kg and 0.5 mg/kg groups. Conclusion: A single higher dose (0.8 mg/kg) of ketamine infusion was a safe and effective treatment strategy for Taiwanese patients with TRD. A 0.8 mg/kg ketamine infusion may achieve optimal blood levels of ketamine and norketamine and may have a superior treatment response in Taiwanese patients.