Introduction Clinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole vs placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task. Methods and analysis PAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to week 12 post-randomisation measured using the Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Performance on the decision-making task will be measured at week 0, week 2 and week 12. Secondary outcomes include anhedonia, anxiety and health economic measures including quality of life, capability, well-being and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties. Discussion Pramipexole is a promising augmentation agent for TRD and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with TRD. Trial registration number [ISRCTN84666271][1] No data are available. The full ethically approved protocol is available here: https://www.fundingawards.nihr.ac.uk/award/16/127/17. [1]: http://ISRCTN84666271

中文翻译：

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PAX-D：一项随机安慰剂对照试验的研究方案，评估普拉克索作为附加治疗对难治性抑郁症患者的疗效和机制

简介 临床抑郁症通常在初级保健中通过心理疗法和抗抑郁药物进行治疗。然而，当患者在抑郁发作期间对至少两种或多种抗抑郁药没有反应时，他们被认为患有难治性抑郁症 (TRD)。以前的小型随机对照试验表明，普拉克索是一种多巴胺 D2/3 受体激动剂，可能对治疗单相和双相抑郁症患者有效，因为已知它会影响动机驱动和奖励处理。PAX-D 将比较普拉克索与安慰剂在 TRD 患者当前抗抑郁药物中添加的效果。此外，PAX-D 将使用概率决策任务研究普拉克索对奖励敏感性的机制影响。方法和分析 PAX-D 将评估来自英国的 TRD 患者的短期（前 12 周）和长期（48 周）的有效性。主要结果将是使用抑郁症状自我报告快速清单 (QIDS-SR16) 测量的从基线到随机化后第 12 周的自我报告抑郁症状的变化。决策任务的表现将在第 0 周、第 2 周和第 12 周进行测量。次要结果包括快感缺失、焦虑和健康经济指标，包括生活质量、能力、幸福感和成本。PAX-D 还将评估普拉克索的不利影响，包括冲动控制困难。讨论 普拉克索是一种有前途的 TRD 增强剂，可能是对现有治疗方案的有用补充。PAX-D 将评估其有效性并测试 TRD 患者的潜在作用机制。试用注册号 [ISRCTN84666271][1] 无可用数据。完整的伦理批准协议可在此处获得：https://www.fundingawards.nihr.ac.uk/award/16/127/17。[1]：http://ISRCTN84666271