Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study).

BACKGROUND: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. METHODS: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology - Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. TRIAL REGISTRATION: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

The Evidence-Based Development of an Intervention to Improve Clinical Health Literacy Practice.

Low health literacy is an issue with high prevalence in the UK and internationally. It has a social gradient with higher prevalence in lower social groups and is linked with higher rates of long-term health conditions, lower self-rated health, and greater difficulty self-managing long-term health conditions. Improved medical services and practitioner awareness of a patient's health literacy can help to address these issues. An intervention was developed to improve General Practitioner and Practice Nurse health literacy skills and practice. A feasibility study was undertaken to examine and improve the elements of the intervention. The intervention had two parts: educating primary care doctors and nurses about identifying and enhancing health literacy (patient capacity to get hold of, understand and apply information for health) to improve their health literacy practice, and implementation of on-screen 'pop-up' notifications that alerted General Practitioners (GPs) and nurses when seeing a patient at risk of low health literacy. Rapid reviews of the literature were undertaken to optimise the intervention. Four General Practices were recruited, and the intervention was then applied to doctors and nurses through training followed by alerts via the practice clinical IT system. After the intervention, focus groups were held with participating practitioners and a patient and carer group to further develop the intervention. The rapid literature reviews identified (i) key elements for effectiveness of doctors and nurse training including multi-component training, role-play, learner reflection, and identification of barriers to changing practice and (ii) key elements for effectiveness of alerts on clinical computer systems including 'stand-alone' notification, automatically generated and prominent display of advice, linkage with practitioner education, and use of notifications within a targeted environment. The findings from the post-hoc focus groups indicated that practitioner awareness and skills had improved as a result of the training and that the clinical alerts reminded them to incorporate this into their clinical practice. Suggested improvements to the training included more information on health literacy and how the clinical alerts were generated, and more practical role playing including initiating discussions on health literacy with patients. It was suggested that the wording of the clinical alert be improved to emphasise its purpose in improving practitioner skills. The feasibility study improved the intervention, increasing its potential usefulness and acceptability in clinical practice. Future studies will explore the impact on clinical care through a pilot and a randomised controlled trial.