For many people who suffer from depression, the condition is not just about feeling down, but also about a loss of motivation and difficulty finding pleasure in activities they used to enjoy. A study conducted in Sweden at Lund University and Region Skåne shows that a medicine used to treat Parkinson's disease can be used as an add-on therapy to alleviate these symptoms in some patients with treatment-resistant depression.
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.
"True team work"
"People often say that research is a team effort, and in this case that's certainly true. This was an advanced mechanistic randomised clinical trial based on strong collaborations across professional, institutional and faculty boundaries. Without the infrastructure required for a well-run research clinic, and without the long-standing collaborations involving many talented staff members and researchers, this study would never have been possible," says Daniel Lindqvist.
The study is an academic clinical trial that was conducted without the involvement of the pharmaceutical industry. It forms part of Region Skåne's and the Faculty of Medicine at Lund University's commitment to clinical therapy research. The research team is led by Daniel Lindqvist from the Unit for Biological and Precision Psychiatry, Department of Clinical Sciences, Lund University, and the administration for psychiatry, rehabilitation and assistive technology, Region Skåne. The project has been carried out in close collaboration with, among others, Tomas Deierborg's research team at the Department of Experimental Medical Science, Åsa Tornberg's research team at the Department of Health Sciences, Åsa Hammar's team at the Department of Clinical Sciences in Lund, Diego Pizzagalli's team at UC Irvine and Johannes Björkstrand's research team at the Department of Psychology at Lund University.
