McAllister-Williams Hamish, Goudie Nicola, Azim Lumbini, Bartle Victoria, Berger Michael, Butcher Chrissie, Chadwick Thomas, Clare Emily, Courtney Paul, Dixon Lyndsey, Duffelen Nichola, Fouweather Tony, Gann William, Geddes John, Gupta Sumeet, Hall Beth, Helter Timea, Hindmarch Paul, Holstein Eva-Maria, Lawrence Ward, Mawson Phil, McKinnon Iain, Milne Adam, Molloy Aisling, Moore Abigail, Morriss Richard, Nakulan Anisha, Simon Judit, Smith Daniel, Stokes-Crossley Bryony, Stokes Paul, Swain Andrew, Walmsley Zoë, Weetman Christopher, Young Allan H, Watson Stuart
Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK.
Northern Centre for Mood Disorders, Newcastle University, Newcastle upon Tyne, UK.
Health Technol Assess. 2025 May;29(21):1-216. doi: 10.3310/HBFC1953.
There are limited options currently recommended in National Institute for Health and Care Excellence guidelines for the treatment of bipolar depression. Pramipexole has been shown to improve mood symptoms in two small pilot studies in such patients.
Primary: to evaluate the clinical effectiveness of pramipexole versus placebo alongside routine mood-stabilising medications over 12 weeks in patients with treatment-resistant bipolar depression. Secondary: evaluate the impact of pramipexole on mood and anxiety, psychosocial function, cost-effectiveness, and safety and tolerability over 48 weeks.
Multicentre, randomised, placebo-controlled trial of pramipexole versus placebo in addition to standard-of-care mood stabilisers. Clinicians, researchers and participants were blinded throughout the duration of the study. Pre-randomisation stage (to adjust antipsychotics or commence mood stabilisers where required) before randomisation. Weekly online assessments of mood and anxiety from randomisation to week 52, with psychosocial function, quality of life and healthcare resource utilisation assessments conducted at regular intervals.
Twenty-one National Health Service trusts and Health Boards across England and Scotland.
Patients aged 18 years and over with a diagnosis of treatment-resistant bipolar depression currently under secondary care mental health services. Aim to randomise 290 participants.
Pramipexole or matched placebo orally once daily, titrated from 0.25 mg to maximum of 2.5 mg (salt weight) depending on efficacy and tolerability.
Depression - Quick Inventory for Depressive Symptomology; anxiety - Generalised Anxiety Disorder-7-item scale; psychosocial functioning - Work and Social Adjustment Scale; hypomania/mania - Altman Self-rating Scale of Mania; tolerability - Treatment Satisfaction Questionnaire for Medication; well-being and quality of life - EuroQol-5 Dimensions, five-level version, ICEpop CAPability measure for Adults and Oxford CAPabilities questionnaire-Mental Health tools.
Thirty-nine participants randomised (18 to pramipexole and 21 to placebo) with 36 providing data for the primary analysis. Pramipexole led to greater reductions in depressive symptoms at 12 weeks compared to placebo [4.4 (4.8) vs. 2.1 (5.1)]: a medium-sized ( = -0.72) but not statistically significant difference (95% confidence interval -0.4 to 6.3; = 0.087). There were some statistically significant positive effects of pramipexole on secondary outcomes (reduction in depressive symptoms at 36 weeks, response and remission rates at trial exit, psychosocial function). Pramipexole was associated with an increased rate of hypomania/manic symptoms, but this appeared to be reduced by coadministration with an antipsychotic. General tolerability of pramipexole was good. There were significant annual gains in health-related quality of life and capability-well-being and tendency towards reduced health and social care costs.
Small sample size and variable follow-up period due to recruitment during COVID-19 pandemic and the trial closing early. Participants limited to those in secondary care mental health services. All assessments only available in English.
No change in clinical practice can be recommended as there was not a significant difference between pramipexole and placebo on the primary efficacy outcome measure. However, there was evidence of positive effects of pramipexole on mood, psychosocial function and quality of life.
Replication in a larger population and research to investigate the impact of coadministration of antipsychotics alongside pramipexole.
This trial is registered as ISRCTN72151939 and EudraCT 2018-2869-18.
This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/154/01) and is published in full in ; Vol. 29, No. 21. See the NIHR Funding and Awards website for further award information.
目前英国国家卫生与临床优化研究所（National Institute for Health and Care Excellence）指南中推荐用于治疗双相抑郁的选择有限。在两项针对此类患者的小型试点研究中，普拉克索已被证明可改善情绪症状。
主要目的：评估在12周内，与安慰剂相比，普拉克索联合常规心境稳定剂对难治性双相抑郁患者的临床疗效。次要目的：评估普拉克索在48周内对情绪和焦虑、心理社会功能、成本效益以及安全性和耐受性的影响。
多中心、随机、安慰剂对照试验，将普拉克索与安慰剂除标准治疗的心境稳定剂外进行比较。在研究期间，临床医生、研究人员和参与者均处于盲态。随机分组前有预随机化阶段（根据需要调整抗精神病药物或开始使用心境稳定剂）。从随机分组到第52周，每周进行在线情绪和焦虑评估，并定期进行心理社会功能、生活质量和医疗资源利用评估。
英格兰和苏格兰的21个国民保健服务信托基金和健康委员会。
年龄在18岁及以上、诊断为难治性双相抑郁且目前接受二级心理健康服务的患者。目标是随机分配290名参与者。
普拉克索或匹配的安慰剂，每日口服一次，根据疗效和耐受性从0.25毫克滴定至最大2.5毫克（盐重量）。
抑郁——抑郁症状快速量表；焦虑——广泛性焦虑障碍7项量表；心理社会功能——工作和社会适应量表；轻躁狂/躁狂——阿尔特曼躁狂自评量表；耐受性——药物治疗满意度问卷；幸福感和生活质量——欧洲五维健康量表（EuroQol-5 Dimensions）、五级版本、成人ICEpop能力量表和牛津能力问卷——心理健康工具。
39名参与者被随机分组（18名接受普拉克索，21名接受安慰剂），36名提供了主要分析数据。与安慰剂相比，普拉克索在12周时导致抑郁症状有更大程度的减轻[4.4（4.8）对2.1（5.1）]：差异为中等大小（=-0.72）但无统计学意义（95%置信区间-0.4至6.3；=0.087）。普拉克索对次要结局有一些统计学上显著的积极影响（36周时抑郁症状减轻、试验结束时的缓解率和缓解反应率、心理社会功能）。普拉克索与轻躁狂/躁狂症状发生率增加相关，但与抗精神病药物联合使用时这种情况似乎有所减少。普拉克索的总体耐受性良好。与健康相关的生活质量和能力幸福感有显著年度改善，且有降低健康和社会护理成本的趋势。
由于在新冠疫情期间招募且试验提前结束，样本量小且随访期可变。参与者仅限于接受二级心理健康服务的患者。所有评估仅提供英文版本。
由于在主要疗效结局指标上普拉克索与安慰剂之间无显著差异，因此不建议改变临床实践。然而，有证据表明普拉克索对情绪、心理社会功能和生活质量有积极影响。
在更大规模人群中重复研究，并研究抗精神病药物与普拉克索联合使用的影响。
本试验注册为ISRCTN72151939和EudraCT 2018 - 2869 - 18。
本奖项由英国国家卫生与保健研究机构（NIHR）卫生技术评估项目资助（NIHR奖项编号：16/154/01），并全文发表于；第29卷，第21期。有关进一步的奖项信息，请参阅NIHR资助和奖项网站。
