. 2021 Jul 5;21(1):334.

doi: 10.1186/s12888-021-03322-y.

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)

Lumbini Azim^{1

2}, Paul Hindmarch^{1

2}, Georgiana Browne³, Thomas Chadwick⁴, Emily Clare¹, Paul Courtney¹, Lyndsey Dixon¹, Nichola Duffelen¹, Tony Fouweather⁴, John R Geddes^{5

6

7}, Nicola Goudie³, Sandy Harvey^{8

9}, Timea Helter¹⁰, Eva-Maria Holstein³, Garry Martin¹, Phil Mawson³, Jenny McCaffery³, Richard Morriss¹¹, Judit Simon^{5

8}, Daniel Smith¹², Paul R A Stokes¹³, Jenn Walker³, Chris Weetman³, Faye Wolstenhulme³, Allan H Young¹³, Stuart Watson^{1

2}, R Hamish McAllister-Williams^{14

15

16}

Affiliations

¹ Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle, UK.
² Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle, UK.
³ Newcastle Clinical Trials Unit, Newcastle University, Newcastle, UK.
⁴ Biostatistics Research Group, Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
⁵ Department of Psychiatry, University of Oxford, Oxford, UK.
⁶ Oxford Health NHS Foundation Trust, Oxford, UK.
⁷ NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
⁸ Patient, Carer and Public Involvement, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁹ Clinical Research Network in North East and North Cumbria, Newcastle upon Tyne, UK.
¹⁰ Department of Health Economics, Center for Public Health, Medical University of Vienna, Vienna, Austria.
¹¹ Division of Psychiatry and Applied Psychology, University of Nottingham, Nottingham, UK.
¹² Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
¹³ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London & South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, London, UK.
¹⁴ Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle, UK. Hamish.McAllister-Williams@newcastle.ac.uk.
¹⁵ Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle, UK. Hamish.McAllister-Williams@newcastle.ac.uk.
¹⁶ Northern Centre for Mood Disorders, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5LP, UK. Hamish.McAllister-Williams@newcastle.ac.uk.

PMID: 34225686
PMCID: PMC8256234
DOI: 10.1186/s12888-021-03322-y

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)

Lumbini Azim et al. BMC Psychiatry. 2021.

. 2021 Jul 5;21(1):334.

doi: 10.1186/s12888-021-03322-y.

Authors

Affiliations

¹ Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle, UK.
² Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle, UK.
³ Newcastle Clinical Trials Unit, Newcastle University, Newcastle, UK.
⁴ Biostatistics Research Group, Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK.
⁵ Department of Psychiatry, University of Oxford, Oxford, UK.
⁶ Oxford Health NHS Foundation Trust, Oxford, UK.
⁷ NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
⁸ Patient, Carer and Public Involvement, The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
⁹ Clinical Research Network in North East and North Cumbria, Newcastle upon Tyne, UK.
¹⁰ Department of Health Economics, Center for Public Health, Medical University of Vienna, Vienna, Austria.
¹¹ Division of Psychiatry and Applied Psychology, University of Nottingham, Nottingham, UK.
¹² Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
¹³ Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London & South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital, London, UK.
¹⁴ Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle, UK. Hamish.McAllister-Williams@newcastle.ac.uk.
¹⁵ Northern Centre for Mood Disorders, Newcastle University Translational and Clinical Research Institute, Newcastle, UK. Hamish.McAllister-Williams@newcastle.ac.uk.
¹⁶ Northern Centre for Mood Disorders, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne, NE4 5LP, UK. Hamish.McAllister-Williams@newcastle.ac.uk.

PMID: 34225686
PMCID: PMC8256234
DOI: 10.1186/s12888-021-03322-y

Abstract

Background: Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson's Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed.

Methods: The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology - Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures.

Trial registration: ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0.

Keywords: Bipolar disorder; Mood stabilisers; Pramipexole; Treatment resistant bipolar depression.

PubMed Disclaimer

Conflict of interest statement

LA, GB, EC, LD, ND, TF, NG, SH, TH, PH, EMH, GM, PM, JM, JS, DS, JW, CW and FW have no competing interests.

TC: Thomas Chadwick reports grants from NIHR (HTA) during the conduct of the study and outside the submitted work.

PC: In last 5 years, Paul Courtney has received speaker fees from Lundbeck. Paul Courtney is a shareholder in GlaxoSmithKline.

JRG: JRG in past 5 years has received research funding from MRC, NIHR, Wellcome. JRG is Director of NIHR Oxford Health Biomedical Research Centre and an Emeritus NIHR senior investigator; the views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health.

RHMW: In the last 5 years, R. Hamish McAllister-Williams has received fees from American Center for Psychiatry & Neurology United Arab Emirates, British Association for Psychopharmacology, European College of Neuropsychophamracology, International Society for Affective Disorders, Janssen-Cilag ltd, LivaNova, Lundbeck, My Tomorrows, OCM Comunicaziona s.n.c., Pfizer, Qatar International Mental Health Conference, Sunovion, Syntropharma, UK Medical Research Council and Wiley; grant support from NIHR Efficacy and Mechanism Evaluation Panel and HTA Panel; and non-financial support from COMPASS Pathways.

RM: Richard Morriss is supported by Nottingham NIHR Biomedical Centre, NIHR MindTech Medical Technology and In Vitro Collaboration and NIHR Applied Research Collaboration East Midlands.

PS: Paul Stokes reports grant funding from NIHR HTA, during the conduct of the study. Paul Stokes reports non-financial support from Janssen Research and Development LLC, personal fees from Frontiers in Psychiatry, personal fees from Allergan, grants from H Lundbeck, grants and non-financial support from Corcept Therapeutics, outside the submitted work.

SW: Stuart Watson has received speaker fees from Lundbeck, the British Association of Psychopharmacology and NIHR grant support.

AY: In the past five years Allan Young has given paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma and COMPASS. AY is Principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression”, “The Effects of Psilocybin on Cognitive Function in Healthy Participants” and “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)”.

Figures

See this image and copyright information in PMC

References

1. Clemente AS, Diniz BS, Nicolato R, Kapczinski FP, Soares JC, Firmo JO, Castro-Costa É. Bipolar disorder prevalence: a systematic review and meta-analysis of the literature. Rev Bras Psiquiatr. 2015;37(2):155–161. doi: 10.1590/1516-4446-2012-1693. - DOI - PubMed
1. Kessing LV, Vradi E, Andersen PK. Life expectancy in bipolar disorder. Bipolar Disord. 2015;17(5):543–548. doi: 10.1111/bdi.12296. - DOI - PubMed
1. Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, Leon AC, Rice JA, Keller MB. The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6):530–537. doi: 10.1001/archpsyc.59.6.530. - DOI - PubMed
1. Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB. A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry. 2003;60(3):261–269. doi: 10.1001/archpsyc.60.3.261. - DOI - PubMed
1. National Institute for Health and Care Excellence . Bipolar disorder: Assessment and management. NICE. 2014. - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Associated data

Actions
- Search in PubMed
- Search in ISRCTN Controlled Trials

Grants and funding

EP-C-17-031/EPA/EPA/United States

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)

Affiliations

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical