Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community.

INTRODUCTION: 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. METHODS AND ANALYSIS: 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 AND DISSEMINATION: 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. TRIAL REGISTRATION NUMBER: UTN: U1111-1294-9310, ACTRN12623000817640p.

The experience of 'treatment-resistant' depression: A qualitative meta-synthesis.

While antidepressants may be effective in treating depression for some people, a third of people do not have an improvement in mood after a trial of two different antidepressants for an adequate duration. These people are diagnosed as having 'treatment-resistant' depression which situates the problem as part of their biological or psychological makeup. We conducted a search of studies that examined this problem from the perspective of people whose depression did not improve on antidepressants. Nine studies were included in a qualitative meta-synthesis that identified four themes across these studies: feeling trapped, disconnection, loss of self, and questioning. The participants experienced considerable distress associated with the constant presence of depression in their lives. While antidepressants may help some people, there is a need for more innovative approaches to the treatment of depression. There is a strong argument for trialling appropriate evidence-based psychotherapy before a person is categorized as having treatment-resistant depression. It is perhaps better to describe the issue as inadequate efficacy of antidepressants to situate the problem with the treatment provided rather than with the person.

The experience of mood disorder and substance use: An integrative review.

WHAT IS KNOWN ON THE SUBJECT?: People with mood disorders often use substances. There are several clinician-driven hypotheses explaining the relationship. WHAT THE PAPER ADDS TO EXISTING KNOWLEDGE?: The paper draws together the existing research on the perceptions of those with lived experience of mood disorders on the reasons for using substances. The participants in the studies identified using substances to manage their mood when treatment to manage their mood was not effective or acceptable, and as an escape from trauma and hardship. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health nurses need an understanding of why people with mood disorders may use substances and the impact of this on their treatment. Mental health nurses need to provide trauma-informed care that emphasizes harm reduction for those who have mood disorders and substance use. ABSTRACT: Introduction Substance use is highly prevalent among people with mood disorders. Effective treatment for these people requires a better understanding of the relationship between both mood and substance use from the perspectives of those with lived experience. Question What are the reasons those with lived experience of mood disorders give for substance use? Method An integrative review was conducted. The Joanna Briggs Institute suite of critical appraisal tools was used to evaluate the quality of individual studies. Data relevant to the review question were extracted, and the results were synthesized into themes. Results Eighteen papers met the eligibility criteria. Three themes were identified across the included studies: Managing my mood, More Effective than prescribed medication, and Escape from trauma and hardship. Discussion This integrative review identified that people with a mood disorder who use substances described choosing to take substances to manage their mood, as an alternative to prescribed medications, and to cope with trauma and social hardships. Implications for Practice Mental health nurses need to provide care that recognizes why people use substances. They need to understand these reasons to provide a harm reduction and trauma-informed model of care. Evidence-based non-pharmacological interventions for mood disorders need to be available as an alternative to medications or as a supplement.