Results from a phase 3 trial show that generic ketamine was safe and effective in treating patients with treatment-resistant depression.
The double-blind, randomized, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Results were published in The British Journal of Psychiatry and online in the Cambridge University Press.
In summary, “…adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period”, and there was a significant difference between patients receiving higher-dose ketamine and those getting the control (remission rates 19.6% for ketamine, 2.0% for midazolam)
See below for more details (taken directly from the study).
Method
Participants received twice-weekly subcutaneous racemic ketamine or midazolam (an active control) for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised and increased to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments (cohort 2).
The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4.
This trial examines the efficacy and safety of repeated racemic ketamine treatments over a 4-week period in adults with TRD, using subcutaneous administration. Midazolam was used as the active control.
Results
The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (flexible, higher doses).
There was a significant difference between treatments for cohort 2 (flexible-dose) (remission rates 19.6% for ketamine, 2.0% for midazolam)
Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h.
Conclusions
Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
This was the largest randomized controlled trial of racemic ketamine tested against placebo in participants with TRD, with cohort 2 alone being larger than total samples in previous trials.