Efficacy and safety of a 4-week course of repeated subcutaneous ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial.

BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam 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, after a Data Safety Monitoring Board recommendation, 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. 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 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). 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.

Propofol and thiopental as anesthetic agents in electroconvulsive therapy: a retrospective study in major depression.

OBJECTIVE: To determine the influence of propofol and thiopental as anesthetics in electroconvulsive therapy (ECT), as regards, seizure duration, electrical charge, clinical efficacy, cardiovascular profile, and presence of adverse cognitive effects. METHODS: A retrospective design including 127 patients who received bilateral ECT for the treatment of a major depressive episode. RESULTS: The mean seizure duration in the propofol group was significantly shorter than in the thiopental group (21.23±6.09 versus 28.24±6.6 7s, P<.001). The mean stimulus charge was 348.22 mC in the propofol group, and 238 mC in the thiopental group (P<.001). Propofol was associated with a lower increase in blood pressure. There were no differences between groups in treatment response or presence of adverse effects. CONCLUSIONS: The anesthetic agent used in ECT might determine differences in parameters such as seizure duration or electrical charge. However, this does not seem to be translated into differences in clinical efficacy or the pattern of adverse effects observed.