The study in brief: treatment-resistant depression // randomised double-blind clinical trial // cause-and-effect // placebo-controlled // 82 participants included in the study, with follow-up conducted after nine weeks // open-label extension for a further six months
The study has been published in Nature Medicine.
Researchers at Lund University and the psychiatric services in Region Skåne have identified a potential new therapy for the condition associated with depression that involves a reduced ability to feel joy, pleasure or motivation – known as anhedonia. Those affected may lose interest in things that they previously found meaningful or rewarding.
The study is an example of what is known as drug repurposing, whereby an already approved medicine is used to treat a different condition. In this study, the researchers investigated pramipexole, which has long been used to treat Parkinson’s disease, as an add-on therapy for depression with marked anhedonia.
“Anhedonia is one of the most debilitating symptoms of depression, and something on which current antidepressant therapies often have only a limited effect. Our findings suggest that pramipexole could be an important new therapy option for this patient group,” says Daniel Lindqvist, a researcher at Lund University and senior consultant in psychiatry at Region Skåne.
All participants in the study had marked anhedonia. Patients were given either pramipexole or a placebo as an add-on to their ongoing medication for nine weeks.
“Those treated with pramipexole for anhedonia showed a more pronounced improvement compared with the placebo group. The effect persisted during a six-month follow-up period among those patients who chose to continue treatment,” says Daniel Lindqvist.
The researchers used advanced brain imaging techniques (7 Tesla fMRI) to investigate the possible biological mechanisms underlying the effect, and activity monitors to assess whether the therapy affected patients’ everyday movement and activity levels.
“We found that pramipexole was linked to a positive effect on the brain’s reward system and increased physical activity in everyday life. This supports the theory that the drug affects the dopamine system, which plays a key role in motivation and reward processing,” says Filip Ventorp, a postdoc at Lund University and resident physician at Region Skåne.
Most patients experienced no major issues with the treatment, and few patients dropped out during the randomized controlled trial. Common side effects included sleep problems, nausea and dizziness, but these could usually be managed by adjusting the dose. Even those who chose to continue with the follow-up phase of the study for a further six months generally responded well to the therapy.
“Efficacy and safety were maintained over time during the follow-up phase, which is particularly relevant in cases of long-term and treatment-resistant depression. Although most participants in our study tolerated the drug well, it is important to monitor any side effects, such as impaired impulse control and daytime fatigue,” says Marie Asp, a psychiatric researcher at Lund University and senior consultant in psychiatry at Region Skåne.
Reference: Ventorp F, Asp M, Olsson S, et al. Efficacy and target engagement of dopamine agonist pramipexole for anhedonic depression: a randomized placebo-controlled trial. Nat Med. 2026. doi: 10.1038/s41591-026-04465-9
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