PAX-D: study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression

• Main Authors: Attenburrow, M.-J (Author), Au-Yeung, S.K (Author), Bogacz, R. (Author), Browning, M. (Author), Chan, F. (Author), Cipriani, A. (Author), Cleare, A. (Author), Cowen, P. (Author), Edwards, C. (Author), Evans, J. (Author), Geddes, J. (Author), Griffiths, J. (Author), Harmer, C.J (Author), Harrison, P.J (Author), Kessler, D. (Author), Lewis, G. (Author), Rendell, J. (Author), Roberts, S. (Author), Shanyinde, M. (Author), Simon, J. (Author), Singh, I. (Author), Watson, S. (Author), Yu, L.-M (Author)
• Format: Article
• Language: English
• Published: NLM (Medline) 2022
• Subjects: adult psychiatry; depression & mood disorders; psychiatry
• Online Access: View Fulltext in Publisher

 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. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.