High-dose Versus Low-dose Oral Ketamine on Control and Relapse of Treatment-resistant Depression: A Randomized, Double-blinded Clinical Trial

Treatment-resistant Depression (TRD) does not respond to conventional treatments. Despite the efforts made to control depression, the outcomes are controversial and inconclusive. New strategies such as ketamine use are accompanied by promising outcomes; however, the best dosage remains a question.

The current study aimed to compare the effect of 1 and 2 mg/kg of oral ketamine in TRD subjects.

The current randomized clinical trial was conducted on 29 patients suffering from TRD. The patients were randomly assigned into two groups of treatment with low dose (1 mg/kg; n = 17) versus high dose (2 mg/kg; n = 12) oral ketamine twice a week for six weeks. The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory-II (BDI-II) were applied to assess the outcomes of the interventions at baseline, within 2, 4, and 6 weeks after the interventions, and then, within a week, a month, and 2 months after the end of the intervention.

Baseline HRDS (P-value = 0.393) and BDI-II (P-value = 0.0.919) were similar in both groups. Neither HDRS (P-value = 0.97) nor BDI-II (P-value = 0.71) had a significant trend of changes when low versus high-dose ketamine uses were compared. The comparison of the frequency of ketamine-related adverse effects revealed a significantly higher incidence of drowsiness (P-value = 0.021) and lightheadedness (P-value = 0.004) in high-dose ketamine.

We achieved no conclusive superiority or efficacy of 1 mg/kg over 2 mg/kg of oral ketamine; however, considering the adverse effects, a 1 mg/kg dose is preferred.