Patients suffering from treatment-resistant depression (TRD) often do not remit from standard treatments. Currently, there is a specific treatment option available for these patients – intranasal esketamine, an enantiomer of ketamine. Meanwhile, some prior studies suggested a high effectiveness of intravenous racemic ketamine in treating TRD. That is why a group of Australian researchers tried to look for and formulate more evidence on the subcutaneous use of ketamine for TRD due to unclear optimal route of ketamine administration. A phase 3, double-blind, randomized, active controlled multicenter trial was therefore conducted at seven mood disorders centers across Australia and New Zealand. Participants received either subcutaneous racemic ketamine twice weekly or midazolam for 4 weeks. The trial first tested the fixed dose protocol of both drugs (0.5 mg/kg ketamine and 0.025 mg/kg midazolam) for safety monitoring in 51 participants. Dosing was then revised to flexible dose for ketamine at 0.5-0.9 mg/kg and midazolam at 0.025-0.045 mg/kg. The primary outcome measure was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. No between-group difference was observed in the first cohort of fixed dose, while subcutaneous racemic ketamine elicited higher remission rate at 19% with the flexible dose protocol compared with 2% of midazolam in 108 participants. The findings from this trial helped to fill in the gaps of knowledge in ketamine use for depression. Future research may consider comparing different types of ketamine, administration routes or treatment strategies.

Reference:

Loo C, et al. Br J Psychiatry. 2023; 1. DOI: 10.1192/bjp.2023.79