Effects of adjunctive brexpiprazole on sleep-wake and circadian parameters in youth with depressive disorders: study protocol for a clinical trial.

INTRODUCTION: Sleep-wake and circadian disturbance is a key feature of mood disorders with a potential causal role and particular relevance to young people. Brexpiprazole is a second-generation antipsychotic medication with demonstrated efficacy as an adjunct to antidepressant treatment for major depressive disorder (MDD) in adults, with preliminary evidence suggesting greater effectiveness in subgroups of depressed patients with sleep disturbances. This clinical trial aims to evaluate the relationships between changes in sleep-wake and circadian parameters and changes in depressive symptoms following adjunctive brexpiprazole treatment in young adults with MDD and sleep-wake disturbance. METHODS AND ANALYSIS: This study is designed as a 16 week (8 weeks active treatment, 8 weeks follow-up) mechanistic, open-label, single-arm, phase IV clinical trial and aims to recruit 50 young people aged 18-30 with MDD and sleep-wake cycle disturbance through an early intervention youth mental health clinic in Sydney, Australia. At baseline, participants will undergo multidimensional outcome assessment and subsequently receive 8 weeks of open-label treatment with brexpiprazole as adjunctive to their stable psychotropic medication. Following 4 weeks of treatment, clinical and self-report measures will be repeated. Ambulatory sleep-wake monitoring will be conducted continuously for the duration of treatment. After 8 weeks of treatment, all multidimensional outcome assessments will be repeated. Follow-up visits will be conducted 4 and 8 weeks after trial completion (including sleep-wake, clinical and self-report assessments). Circadian rhythm biomarkers including salivary melatonin, cortisol and core body temperature will be collected during an in-lab assessment. Additionally, metabolic, inflammatory and genetic risk markers will be collected at baseline and after 8 weeks of treatment. ETHICS AND DISSEMINATION: This trial protocol has been approved by the Human Research Ethics Committee of the Sydney Local Health District (X19-0417 and 2019/ETH12986, Protocol Version 1-3, dated 25 February 2021). The results of this study, in deidentified form, will be disseminated through publication in peer-reviewed journals, scholarly book chapters, presentation at conferences and publication in conference proceedings. TRIAL REGISTRATION NUMBER: ACTRN12619001456145.

Protocol for a young adult mental health (Uspace) cohort: personalising multidimensional care in young people admitted to hospital.

INTRODUCTION: Currently, the literature on personalised and measurement-based mental healthcare is inadequate with major gaps in the development and evaluation of 21st century service models. Clinical presentations of mental ill health in young people are heterogeneous, and clinical and functional outcomes are often suboptimal. Thus, treatments provided in a person-centred and responsive fashion are critical to meet the unique needs of young people and improve individual outcomes. Personalised care also requires concurrent assessment of factors relating to outcomes and underlying neurobiology. This study builds on a completed feasibility study and will be the first to incorporate clinical, cognitive, circadian, metabolic and hormonal profiling with personalised and measurement-based care in a cohort of young people admitted to hospital. METHODS AND ANALYSIS: This prospective, transdiagnostic, observational study will be offered to all young people between the ages of 16 and 30 years admitted to the inpatient unit of the participating centre. In total, 400 participants will be recruited. On admission to hospital, young people will undergo clinical and diagnostic assessment, cognitive testing, self-report questionnaires, metabolic and hormonal data collection, and anthropomorphic measurements. Participants will wear an actigraphy watch for at least 1 week during admission to measure circadian patterns and sleep-wake cycles. A feedback session between clinician and participant will occur after clinical and other laboratory assessments to tailor individual treatment plans, explain the ongoing process of measurement-based care, and provide participant and family education. Associations between cognitive impairments, disturbed sleep-wake behaviours, circadian rhythms, clinical symptoms and functional impairments will be evaluated to improve the understanding of parameters affecting clinical outcomes. ETHICS AND DISSEMINATION: This study protocol was approved by the Human Research Ethics Committees of the University of Sydney (HREC USYD 2015/867) and St Vincent's Hospital (HREC SVH 17/045). This study will be published on completion in a peer-reviewed journal.