Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community.
Ben Beaglehole, Richard Porter, Katie M. Douglas, Cameron James Lacey, Aroha de Bie, Jennifer Jordan, Charlie Mentzel, Bridgette Thwaites, Jenni Manuel, Greg Murray, Christopher M. Frampton, Paul Glue
BMJ Open May 1, 2024 DOI: 10.1136/bmjopen-2024-084844 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Adults aged 18–65 with treatment-resistant major depressive disorder |
| Intervention | Oral ketamine |
| Duration | 8-week intervention, 12-week follow-up |
| Topics | Depression Esketamine Ketamine |
| Keywords | Adult psychiatry Psychosocial intervention Depression treatment Ketamine therapy Mental health interventions Psychosocial therapy |
| Citations | 5 |
| Key findings | The trial aims to determine if adding behavioral activation therapy to oral ketamine reduces relapse rates by more than 20% compared to ketamine alone in treatment-resistant depression. |
Abstract
Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine. This is a prospectively registered, two-centre, single-blind RCT. We aim to recruit 60 participants with TR-MDD aged between 18 and 65 years. Participants will be randomised to 8 weeks of oral ketamine and BAT, or 8 weeks of oral ketamine alone. Feasibility will be assessed by tracking attendance for ketamine and BAT, acceptability of treatment measures and retention to the study follow-up protocol. The primary efficacy outcome measure is the Montgomery-Asberg Depression Rating Scale (MADRS) measured weekly during treatment and fortnightly during 12 weeks of follow-up. Other outcome measures will assess the tolerability of ketamine and BAT, cognition and activity (using actigraphy). Participants will be categorised as non-responders, responders, remitters and relapsed during follow-up. MADRS scores will be analysed using a linear mixed model. For a definitive follow-up RCT study to be recommended, the recruitment expectations will be met and efficacy outcomes consistent with a >20% reduction in relapse rates favouring the BAT and ketamine arm will be achieved. Ethics approval was granted by the New Zealand Central Health and Disability Ethics Committee (reference: 2023 FULL18176). Study findings will be reported to participants, stakeholder groups, conferences and peer-reviewed publications. UTN: U1111-1294-9310, ACTRN12623000817640p.
Comparable studies
Other randomized controlled trials on ketamine for depression, most cited first.