Oxford study finds Parkinson’s drug pramipexole effective for treatment-resistant depression, with benefits lasting up to a year
A drug traditionally used to treat Parkinson’s disease could soon transform care for people with severe, treatment resistant depression, according to new research from the University of Oxford. In a major clinical trial, the medication pramipexole significantly reduced symptoms in patients who hadn’t responded to standard antidepressants, offering a potential lifeline to thousands living with chronic depression.
Pramipexole is a dopamine agonist primarily prescribed for Parkinson’s disease and restless legs syndrome (RLS). It acts by stimulating dopamine receptors in the brain, helping to alleviate movement-related symptoms such as tremors and stiffness.
The research is supported by the National Institute for Health and Care Research (NIHR) and published in The Lancet Psychiatry.
The largest clinical trial to date reveals surprising findings
The trial included 150 patients with treatment resistant depression, with equal numbers receiving 48 weeks of pramipexole or a placebo alongside ongoing antidepressant medication.
The researchers found that the group taking pramipexole experienced a significant reduction in symptoms by week twelve of treatment, with the benefits persisting over a year. However, significant side effects were reported, such as nausea, sleep disturbance, and dizziness, with around one in five people on pramipexole dropping out of the trial as a result.
Professor Michael Browning, from the Department of Psychiatry, University of Oxford, and workstream lead in Mood Disorders for the NIHR Mental Health-Translational Research Collaboration (MH-TRC) Mission, who led the trial, said: “Effectively treating people who have not responded to first-line interventions for depression is a pressing clinical problem and there has long been an urgent need to find new treatments.
‘These findings on pramipexole are a significant breakthrough for patients for whom antidepressants and other treatments and therapies have not worked.
‘Pramipexole is a medicine licensed for Parkinson’s disease and works by boosting the brain chemical dopamine. This differs from the majority of other antidepressant medications that act on brain serotonin and may explain why pramipexole was so helpful in this study.
‘We now need more research focusing on reducing the side effects of pramipexole, evaluating its cost-effectiveness, and comparing it with other add-on treatments.”
Current treatment resistant depression treatments have limited effectiveness
Current guidelines for individuals with treatment-resistant depression suggest adding new medications, such as lithium or antipsychotics, to ongoing antidepressant therapies. However, these options have limited effectiveness and do not work for everyone.
Phil Harvey, 72, from Oxfordshire, was diagnosed with depression 20 years ago and tried different tablets and counseling, but nothing worked. Eventually, he had to take a year off work before retiring. He started on the trial in 2022.
He said: ‘Within a few weeks, I felt the effects; it was amazing. I kept a diary that they gave us to track my mood, motivation, and how it improved. It was dragging me out of this dark black hole that I’ve been in for years.’
Participants were recruited from all over the country, including through the NIHR-funded MH-TRC Mission mood disorder clinics. Although these clinics are based in Oxford, they operate nationwide. They primarily assess patients with complex mood disorders remotely and offer opportunities for enrollment in research studies. Additionally, the network can support primary care services by providing assessment and treatment advice for patients who have not responded to initial treatments.
