A drug used for Parkinson's disease has been shown to be effective in reducing the symptoms of difficult to treat depression, in a study led by the University of Oxford.
In the largest clinical trial to date, pramipexole was found to be substantially more effective than a placebo at reducing the symptoms of treatment resistant depression (TRD) over the course of nearly a year, when added to ongoing antidepressant medication.
The trial, supported by National Institute for Health and Care Research (NIHR) and published in The Lancet Psychiatry, included 150 patients with treatment resistant depression, with equal numbers receiving 48 weeks of pramipexole or a placebo, alongside ongoing antidepressant medication.
Overall, the group taking pramipexole experienced a significant and substantial reduction in symptoms by week twelve of treatment, with the benefits persisting over the course of a year. However, there were also significant side effects, 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 which 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.'
Previous research into using the drug for depression had shown promise, but there had been limited data on its long-term outcomes and side effects until now.
Current guidelines for people with treatment resistant depression recommend adding new treatments, such as lithium or antipsychotics, to ongoing antidepressant treatment, but these 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 counselling 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 which they gave us on how my mood was, 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 across the country, including as part of the NIHR-funded MH-TRC Mission mood disorder clinics, which are hosted at Oxford but located across the country. The clinics efficiently, and largely remotely, assess patients with difficult to treat mood disorders and offer them enrolment in research studies. The network can also support primary care services by providing assessment and treatment advice for patients who have not responded to initial treatment.
This new paper ' Pramipexole augmentation for the acute phase of treatment-resistant, unipolar depression: a placebo-controlled, double-blind, randomised trial in the UK' is published in The Lancet Psychiatry.
