This randomized, double-blinded, midazolam-controlled crossover trial (n=40) aims to identify clinical features that predict response to a single dose of intravenous (IV) ketamine in patients with treatment-resistant depression (TRD).
Led by Abraham Nunes from Nova Scotia Health Authority, the study seeks to address the short-lived effects and resource-intensive nature of IV ketamine treatment. Over the course of one year, 40 participants will be recruited and randomized to receive either ketamine followed by an active placebo or vice versa. Various clinical data will be collected through interviews, questionnaires, actigraphy, speech sampling, EEG, and computerized tasks to evaluate predictors of rapid and sustained response at different time points.
The study design includes a 20-day washout period between infusions to establish comparable baselines. Objective depression ratings will be measured using the Montgomery-Åsberg Depression Rating Scale (MADRS), while secondary outcomes include measures of anxiety, anhedonia, sleep, circadian rhythms, fatigue, and psychomotor behaviour. Eligible participants must have a documented diagnosis of MDD or bipolar disorder meeting DSM-5 criteria and have failed at least two antidepressant medications. Exclusion criteria include pregnancy, allergies to ketamine or midazolam, substance use disorders, and certain medical comorbidities.
The study started on January 19, 2024, with an estimated completion date in February 2025. For further details, interested parties can contact Vanessa Pardo at Nova Scotia Health Authority.
Trial Details
For patients with treatment-resistant depression (TRD), a single low dose of intravenous (IV) ketamine can help relieve symptoms as quickly as 24 hours later. The main problem with IV ketamine for TRD is that the effect is short-lived, lasting only days to 1 or 2 weeks. Furthermore, IV ketamine is a resource-intensive treatment, and the safety of long-term, repeated use for depression is unknown. To provide this treatment in a safe and cost-effective way, Investigators must allocate it efficiently to those patients who have the greatest need and probability of benefit. Therefore, this project aims to find clinical features (signs, symptoms, and parts of a patient's history) that will help predict which patients are most likely to respond to a single dose of IV ketamine for TRD. This will help guide patient selection and triaging. Investigators will recruit 40 participants with TRD over one year, and randomize them to one of two conditions (ketamine followed by an active placebo 3-weeks later, or vice versa). With clinical data collected through detailed interviews, questionnaires, actigraphy, speech sampling, electroencephalography (EEG), and computerized tasks, this study design will let us evaluate how well such factors predict (A) rapid response at 24-hours, and (B) sustained response at 7 and 14 days.Trial Number NCT05625555