A drug commonly used for Parkinson’s disease has shown strong potential in treating people with depression that does not respond to typical medications, according to a new study led by the University of Oxford.
The study found that pramipexole, a drug that boosts dopamine levels in the brain, significantly reduced symptoms of treatment-resistant depression (TRD) when taken alongside regular antidepressants. The large-scale clinical trial, published in The Lancet Psychiatry and supported by the National Institute for Health and Care Research (NIHR), tracked 150 patients over the course of 48 weeks.
Participants were split evenly between those receiving pramipexole and those given a placebo, with both groups continuing their existing antidepressant treatments. By week 12, those taking pramipexole reported a noticeable and lasting improvement in mood and motivation—an effect that persisted through nearly a year of follow-up.
However, side effects were common. Around 20% of patients on pramipexole dropped out of the study due to issues like nausea, dizziness, and trouble sleeping.
A New Option for Persistent Depression
Professor Michael Browning, lead researcher from Oxford’s Department of Psychiatry and the NIHR’s Mood Disorders programme, highlighted the importance of the findings.
“Treating people who haven’t responded to first-line depression treatments is a major challenge,” Browning said. “This study is a real breakthrough for those patients.”
What makes pramipexole different, he explained, is that it targets dopamine—a brain chemical linked to reward and motivation—unlike most antidepressants, which focus on serotonin.
Although previous studies hinted at its potential for depression, this is the first large trial to show its benefits and long-term safety in such patients.
Real-World Impact
One participant, Phil Harvey, 72, from Oxfordshire, shared how the treatment changed his life. Diagnosed with depression two decades ago, Harvey tried numerous medications and therapy sessions without success. Eventually, he had to stop working.
He joined the trial in 2022.
“Within a few weeks, I felt the effects. It was amazing,” he said. “It dragged me out of this dark black hole I’d been in for years.”
Participants like Phil were enrolled from across the UK, many through specialized mood disorder clinics funded by the NIHR. These clinics not only offer trial opportunities but also help general practitioners manage complex cases.
What’s Next?
Currently, options for TRD include add-on drugs like lithium or antipsychotics, but these treatments often have limited success. Researchers believe pramipexole could offer a valuable alternative, especially for those not helped by existing strategies.
Still, experts caution that more work is needed. Professor Browning emphasized the need to further investigate how to reduce side effects, assess cost-effectiveness, and compare pramipexole to other treatments before it can be widely recommended.
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