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Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression : a randomized placebo-controlled trial

Ventorp, Filip LU ; Asp, Marie LU ; Olsson, Sofia LU orcid ; Lindahl, Jesper LU ; Möller, Stefan LU orcid ; Svensson, Martina LU orcid ; Ängeby, Filip LU ; Pravdinske, Armida LU ; Tjernberg, Johanna LU orcid and Schrey, Susann LU , et al. (2026) In Nature Medicine
Abstract

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith-Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized,... (More)

Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith-Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: -4.04, 95% confidence interval: -6.89 to -1.18, P = 0.006, Hedges' g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 .

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publication status
epub
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in
Nature Medicine
publisher
Nature Publishing Group
external identifiers
  • scopus:105041493004
  • pmid:42286321
ISSN
1546-170X
DOI
10.1038/s41591-026-04465-9
language
English
LU publication?
yes
additional info
© 2026. The Author(s).
id
ba91b32a-b543-4672-a330-3901fc87a377
date added to LUP
2026-06-14 11:11:45
date last changed
2026-09-15 05:39:16
@article{ba91b32a-b543-4672-a330-3901fc87a377,
  abstract     = {{<p>Anhedonia is a core and disabling symptom of mood disorders with limited treatment options. We evaluated the efficacy and safety of the dopamine agonist pramipexole in patients with mood disorders characterized by clinically significant anhedonia. In this single-center, randomized, double-blind, placebo-controlled trial, adults with major depressive disorder, dysthymia or bipolar depression and elevated Snaith-Hamilton Pleasure Scale (SHAPS) scores were assigned (1:1) to flexible dose, once-daily oral pramipexole as add-on treatment or placebo for 9 weeks. The primary outcome was change in SHAPS score from baseline to week 9. Analyses were conducted in the modified intention-to-treat population. Eighty-five participants were randomized, and 82 were included in the analysis. The primary outcome was met: pramipexole was associated with a greater reduction in SHAPS scores compared to placebo (mean difference: -4.04, 95% confidence interval: -6.89 to -1.18, P = 0.006, Hedges' g = 0.62). Exploratory analyses indicated that pramipexole was associated with increased light physical activity and relative preservation of reward-related ventral striatal activation. Improvements in anhedonia were sustained during a 6-month open-label extension. Pramipexole was generally well tolerated compared to placebo. Pramipexole significantly improved anhedonia and showed a favorable safety profile, supporting its potential as an augmentation strategy in mood disorders. ClinicalTrials.gov identifiers: NCT05355337 and NCT05825235 .</p>}},
  author       = {{Ventorp, Filip and Asp, Marie and Olsson, Sofia and Lindahl, Jesper and Möller, Stefan and Svensson, Martina and Ängeby, Filip and Pravdinske, Armida and Tjernberg, Johanna and Schrey, Susann and Ståhl, Darya and Magnusson, Viktor and Eliasson, Emilia and Agelii-Weber, Anna and Stålhammar, Erika and van Westen, Danielle and Deierborg, Tomas and Månsson, Kristoffer N T and Pizzagalli, Diego A and Hammar, Åsa and Tornberg, Åsa B and Björkstrand, Johannes and Lindqvist, Daniel}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression : a randomized placebo-controlled trial}},
  url          = {{http://dx.doi.org/10.1038/s41591-026-04465-9}},
  doi          = {{10.1038/s41591-026-04465-9}},
  year         = {{2026}},
}