New Zealand clinicians developed practical guidelines for using ketamine to treat treatment-resistant major depressive disorder in publicly funded specialist mental health services. The guidelines offer two treatment pathways: a test of responsiveness with intramuscular ketamine followed by a 3-month course of oral ketamine, aiming to maximize short-term benefits. The guidance was created through consultation with senior leadership, clinical pharmacy, psychiatrists, nursing, service users, and Māori mental health workers.
A randomized controlled trial will test the feasibility of adding behavioral activation therapy (BAT) to oral ketamine for treatment-resistant major depressive disorder. The study aims to recruit 60 adults aged 18–65 years, randomizing them to eight weeks of oral ketamine with BAT or oral ketamine alone. Feasibility will be measured by attendance, acceptability, and retention. The primary efficacy outcome is the Montgomery-Asberg Depression Rating Scale, assessed weekly during treatment and fortnightly during 12 weeks of follow-up. For a definitive trial to be recommended, the study must meet recruitment targets and show a greater than 20% reduction in relapse rates favoring the combined treatment arm.