TY - JOUR
T1 - PAX-D
T2 - 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
AU - Au-Yeung, Sheena Kristine
AU - Griffiths, James
AU - Roberts, Sophie
AU - Edwards, Chloe
AU - Yu, Ly Mee
AU - Bogacz, Rafal
AU - Rendell, Jennifer
AU - Attenburrow, Mary Jane
AU - Watson, Stuart
AU - Chan, Fiona
AU - Cipriani, Andrea
AU - Cleare, Anthony
AU - Harmer, Catherine J.
AU - Kessler, David
AU - Evans, Jonathan
AU - Lewis, Glyn
AU - Singh, Ilina
AU - Simon, Judit
AU - Harrison, Paul J.
AU - Cowen, Phil
AU - Shanyinde, Milensu
AU - Geddes, John
AU - Browning, Michael
N1 - Funding Information:
This study is funded by the NIHR Efficacy and Mechanism Evaluation Programme (16/127/17) and supported by the NIHR Oxford Health Biomedical Research Centre. The NIHR is not involved in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.
Funding Information:
MB has acted as a consultant for Janssen Research, P1vital and CHDR, owns shares in P1vital Products and was previously a paid employee of P1vital. JoG has research funding from NIHR and Westminster Foundation. M-JA is supported by the NIHR Oxford cognitive health Clinical Research Facility. SW has received honoraria for talks from Lundbeck. All other authors declare no conflict of interests.
Funding Information:
This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre, Oxford (grant BRC-1215-20005), and the NIHR Oxford cognitive health Clinical Research Facility. ACi is also supported by an NIHR Research Professorship (grant RP-2017-08-ST2-006) and by the NIHR Oxford and Thames Valley Applied Research Collaboration.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.
PY - 2022/5/1
Y1 - 2022/5/1
N2 - 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.
AB - 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.
KW - adult psychiatry
KW - depression & mood disorders
KW - psychiatry
UR - http://www.scopus.com/inward/record.url?scp=85128596245&partnerID=8YFLogxK
U2 - 10.1136/ebmental-2021-300282
DO - 10.1136/ebmental-2021-300282
M3 - Article
C2 - 34810175
AN - SCOPUS:85128596245
SN - 1468-960X
VL - 25
SP - 77
EP - 83
JO - Evidence-based mental health
JF - Evidence-based mental health
IS - 2
M1 - e300282
ER -