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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

Lookup NU author(s): Dr Stuart Watson



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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

Publication metadata

Author(s): Au-Yeung SK, Griffiths J, Roberts S, Edwards C, Yu L-M, Bogacz R, Rendell J, Attenburrow M-J, Watson S, Chan F, Cipriani A, Cleare A, Harmer CJ, Kessler D, Evans J, Lewis G, Singh I, Simon J, Harrison PJ, Cowen P, Shanyinde M, Geddes J, Browning M

Publication type: Article

Publication status: Published

Journal: Evidence-Based Mental Health

Year: 2022

Volume: 25

Issue: 2

Pages: 77-83

Print publication date: 01/05/2022

Online publication date: 22/11/2021

Acceptance date: 02/04/2018

Date deposited: 09/05/2022

ISSN (print): 1362-0347

ISSN (electronic): 1468-960X

Publisher: BMJ Publishing Group


DOI: 10.1136/ebmental-2021-300282

PubMed id: 34810175


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