Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle, UK.
Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle, UK.
BMC Psychiatry. 2021 Jul 5;21(1):334. doi: 10.1186/s12888-021-03322-y.
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.
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.
ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.
治疗抵抗性双相情感障碍（TRBD）是导致双相情感障碍（BD）相关疾病负担的主要因素之一。接受双相情感障碍抑郁发作的人的治疗选择仅限于英国国家卫生与保健研究院列出的三种干预措施：拉莫三嗪、喹硫平和奥氮平，其中后两者往往不能很好耐受。因此，大多数患有 BD 的抑郁患者尽管疗效有限，但仍被开抗抑郁药。这表明需要额外的干预措施。普拉克索已被证明可改善抑郁动物模型、帕金森病患者和两项普拉克索治疗目前抑郁的 BD 患者的原理验证试验中的情绪症状。
由英国国家卫生研究院资助的 PAX-BD 研究旨在扩展先前的发现，除了情绪稳定剂外，还评估普拉克索对 TRBD 患者的疗效、安全性和健康经济影响。该研究采用随机、双盲、安慰剂对照设计，在英国国家卫生服务的自然环境中进行。该研究还包括一项内部试点研究，以检验研究设计的可行性和可接受性。从英国多达 40 个心理健康信托的国家卫生服务二级保健服务中筛选出 TRBD 患者，目标是在预随机化阶段招募大约 414 名参与者，以达到 290 名随机参与者的目标。主要安全性和疗效测量指标是在随机分组后 12 周进行，对参与者进行随访至 52 周。主要结局是使用贝克抑郁自评量表评估抑郁症状。次要结局包括焦虑、躁狂症状的变化、耐受性、可接受性、生活质量和成本效益。使用在线实施的自我报告工具远程收集结局测量指标，并通过电话进行观察者评定评估。协方差分析（ANCOVA）将用于检验治疗臂之间评分量表差异，取决于每周自我报告测量的完成情况。混合效应线性回归模型也可能用于解释重复测量。
ISRCTN72151939。于 2019 年 8 月 28 日注册，网址：http://www.isrctn.com/ISRCTN72151939。方案版本：2021 年 2 月 4 日，第 9.0 版。
