A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)

Hamish  McAllister-Williams; Nicola Goudie; Lumbini Azim; Victoria  Bartle; Michael  Berger; Chrissie Butcher; Thomas Chadwick; Emily Clare; Paul Courtney; Lyndsey Dixon; Nicola Duffelen; Tony Fouweather; William Gann; John Geddes; Sumeet  Gupta; Bethany Hall; Timea Helter; Paul Hindmarch; Eva-Maria Holstein; Ward  Lawrence; Phil Mawson; Iain McKinnon; Adam  Milne; Aisling Molloy; Abigail  Moore; Richard Morris; Anisha  Nakulan; Judit Simon; Daniel Smith; Bryony Stokes-Crossley; Paul Stokes; Andrew Swain; Adeola Taiwo; Zoe Walmsley; Christopher  Weetman; Allan Young; Stuart Watson

doi:10.1177/02698811241309622

A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)

Hamish McAllister-Williams, Nicola Goudie, Lumbini Azim, Victoria Bartle, Michael Berger, Chrissie Butcher, Thomas Chadwick, Emily Clare, Paul Courtney, Lyndsey Dixon, Nicola Duffelen, Tony Fouweather, William Gann, John Geddes, Sumeet Gupta, Bethany Hall, Timea Helter, Paul Hindmarch, Eva-Maria Holstein, Ward LawrencePhil Mawson, Iain McKinnon, Adam Milne, Aisling Molloy, Abigail Moore, Richard Morris, Anisha Nakulan, Judit Simon, Daniel Smith, Bryony Stokes-Crossley, Paul Stokes, Andrew Swain, Adeola Taiwo, Zoe Walmsley, Christopher Weetman, Allan Young, Stuart Watson

Research output: Contribution to journal › Article › peer-review

28 Downloads (Pure)

Abstract

Background: Options for ‘treatment-resistant bipolar depression’ (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option. Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD. Methods: A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (n = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up. Results: Pramipexole (n = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (n = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (d = −0.72) but not statistically significant difference (95% CI: −0.4 to 6.3, p = 0.087). Similarly, there was a non-significant approximate 2-point (d = −0.76) improvement in pleasure at 6 weeks (95% CI: −0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85–10.71) and psychosocial function (5.36 points: 95% CI: 0.38–10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; p = 0.026) and remission (31% vs 0%; p = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated. Conclusions: Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.

Original language	English
Journal	Journal of Psychopharmacology
DOIs	https://doi.org/10.1177/02698811241309622
Publication status	Published - 20 Jan 2025

Access to Document

10.1177/02698811241309622

mcallister-williams-et-al-2025-a-randomised-double-blind-placebo-controlled-trial-of-pramipexole-in-addition-to-moodFinal published version, 930 KBLicence: CC BY

Cite this

McAllister-Williams, H., Goudie, N., Azim, L., Bartle, V., Berger, M., Butcher, C., Chadwick, T., Clare, E., Courtney, P., Dixon, L., Duffelen, N., Fouweather, T., Gann, W., Geddes, J., Gupta, S., Hall, B., Helter, T., Hindmarch, P., Holstein, E.-M., ... Watson, S. (2025). A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study). Journal of Psychopharmacology. https://doi.org/10.1177/02698811241309622

@article{47fe2a630a954dbc937fd753f24ba6a4,

title = "A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)",

abstract = "Background: Options for {\textquoteleft}treatment-resistant bipolar depression{\textquoteright} (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option. Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD. Methods: A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (n = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up. Results: Pramipexole (n = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (n = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (d = −0.72) but not statistically significant difference (95% CI: −0.4 to 6.3, p = 0.087). Similarly, there was a non-significant approximate 2-point (d = −0.76) improvement in pleasure at 6 weeks (95% CI: −0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85–10.71) and psychosocial function (5.36 points: 95% CI: 0.38–10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; p = 0.026) and remission (31% vs 0%; p = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated. Conclusions: Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.",

author = "Hamish McAllister-Williams and Nicola Goudie and Lumbini Azim and Victoria Bartle and Michael Berger and Chrissie Butcher and Thomas Chadwick and Emily Clare and Paul Courtney and Lyndsey Dixon and Nicola Duffelen and Tony Fouweather and William Gann and John Geddes and Sumeet Gupta and Bethany Hall and Timea Helter and Paul Hindmarch and Eva-Maria Holstein and Ward Lawrence and Phil Mawson and Iain McKinnon and Adam Milne and Aisling Molloy and Abigail Moore and Richard Morris and Anisha Nakulan and Judit Simon and Daniel Smith and Bryony Stokes-Crossley and Paul Stokes and Andrew Swain and Adeola Taiwo and Zoe Walmsley and Christopher Weetman and Allan Young and Stuart Watson",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = jan,

day = "20",

doi = "10.1177/02698811241309622",

language = "English",

journal = "Journal of Psychopharmacology",

issn = "0269-8811",

publisher = "SAGE Publications Ltd STM",

}

McAllister-Williams, H, Goudie, N, Azim, L, Bartle, V, Berger, M, Butcher, C, Chadwick, T, Clare, E, Courtney, P, Dixon, L, Duffelen, N, Fouweather, T, Gann, W, Geddes, J, Gupta, S, Hall, B, Helter, T, Hindmarch, P, Holstein, E-M, Lawrence, W, Mawson, P, McKinnon, I, Milne, A, Molloy, A, Moore, A, Morris, R, Nakulan, A, Simon, J, Smith, D, Stokes-Crossley, B, Stokes, P, Swain, A, Taiwo, A, Walmsley, Z, Weetman, C, Young, A & Watson, S 2025, 'A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)', Journal of Psychopharmacology. https://doi.org/10.1177/02698811241309622

TY - JOUR

T1 - A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)

AU - McAllister-Williams, Hamish

AU - Goudie, Nicola

AU - Azim, Lumbini

AU - Bartle, Victoria

AU - Berger, Michael

AU - Butcher, Chrissie

AU - Chadwick, Thomas

AU - Clare, Emily

AU - Courtney, Paul

AU - Dixon, Lyndsey

AU - Duffelen, Nicola

AU - Fouweather, Tony

AU - Gann, William

AU - Geddes, John

AU - Gupta, Sumeet

AU - Hall, Bethany

AU - Helter, Timea

AU - Hindmarch, Paul

AU - Holstein, Eva-Maria

AU - Lawrence, Ward

AU - Mawson, Phil

AU - McKinnon, Iain

AU - Milne, Adam

AU - Molloy, Aisling

AU - Moore, Abigail

AU - Morris, Richard

AU - Nakulan, Anisha

AU - Simon, Judit

AU - Smith, Daniel

AU - Stokes-Crossley, Bryony

AU - Stokes, Paul

AU - Swain, Andrew

AU - Taiwo, Adeola

AU - Walmsley, Zoe

AU - Weetman, Christopher

AU - Young, Allan

AU - Watson, Stuart

PY - 2025/1/20

Y1 - 2025/1/20

N2 - Background: Options for ‘treatment-resistant bipolar depression’ (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option. Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD. Methods: A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (n = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up. Results: Pramipexole (n = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (n = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (d = −0.72) but not statistically significant difference (95% CI: −0.4 to 6.3, p = 0.087). Similarly, there was a non-significant approximate 2-point (d = −0.76) improvement in pleasure at 6 weeks (95% CI: −0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85–10.71) and psychosocial function (5.36 points: 95% CI: 0.38–10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; p = 0.026) and remission (31% vs 0%; p = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated. Conclusions: Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.

AB - Background: Options for ‘treatment-resistant bipolar depression’ (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option. Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD. Methods: A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser (n = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up. Results: Pramipexole (n = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo (n = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized (d = −0.72) but not statistically significant difference (95% CI: −0.4 to 6.3, p = 0.087). Similarly, there was a non-significant approximate 2-point (d = −0.76) improvement in pleasure at 6 weeks (95% CI: −0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85–10.71) and psychosocial function (5.36 points: 95% CI: 0.38–10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; p = 0.026) and remission (31% vs 0%; p = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated. Conclusions: Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.

UR - http://www.scopus.com/inward/record.url?scp=85215535157&partnerID=8YFLogxK

U2 - 10.1177/02698811241309622

DO - 10.1177/02698811241309622

M3 - Article

SN - 0269-8811

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

ER -

A randomised double-blind, placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment-resistant bipolar depression (the PAX-BD study)

Abstract

Access to Document

Other files and links

Fingerprint

Cite this