An Oxford University-led study has looked into whether pramipexole could make a difference for people with depression – and it looks like it just might.
The study involved individuals who had weathered, on average, three to four unsuccessful antidepressant regimens, with a median depressive episode length of eight and a half years. They were treated with pramipexole, a dopamine D2/D3 receptor agonist traditionally used to treat Parkinson’s disease and restless legs syndrome. It’s not your standard antidepressant, and that’s the point. Traditional SSRIs often fizzle out in the face of anhedonia – the clinical term for losing the ability to enjoy everyday activities such as eating chocolate or dancing. Dopamine, the pleasure and reward neurotransmitter, might be just the chemical sherpa these patients need to climb out of their mental valleys.
Pramipexole (titrated up to 2.5 mg) was added to participants’ existing antidepressants and showed a significantly greater reduction in depression scores (QIDS-SR16) than those in the placebo group. That’s a nearly four-point difference and a Cohen’s d effect size of 0.87. For non-statisticians, that’s good.
44 percent in the pramipexole group hit the 50 percent symptom reduction mark, versus only 16 percent in the placebo group. Remission rates were also higher: 28 percent versus 8 percent. That’s pharmacology. These results held steady over 48 weeks.
Pramipexole might boost mood, but it also brings along an entourage of adverse events, including nausea, headaches, dizziness, and sleep disturbances. 20 percent of participants in the pramipexole group discontinued the drug due to side effects, compared to just five percent in the placebo arm. Impulse control disorders, a notorious dopamine agonist side effect, occurred in two cases.
So, it works. But at what cost? If you’re the prescribing psychiatrist, be ready for a bit of a balancing act. Or as one might say, welcome to the fine art of pharmacological matchmaking.
From a drug development perspective, the PAX-D trial underscores the potential – and the perils – of repurposing existing agents for psychiatric use. Pramipexole wasn’t born to fight depression, but it seems to be picking up the slack where serotonin falters.
This could represent a call to revisit the dopaminergic pathway. Could a modified-release formulation mitigate side effects? Could combination therapies with antiemetics improve adherence? Could this be a stepping stone to new, dopamine-focused antidepressants? Pramipexole is not likely to replace Selective Serotonin Reuptake Inhibitors (SSRIs) or Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) anytime soon, but it’s making a compelling case for a seat at the augmentation table. For patients stuck in the pharmacological slow lane, it could offer some much-needed acceleration, even if they have to endure a few bumps along the way. In short: dopamine might not solve all your problems, but when serotonin isn’t cutting it, it’s nice to have options. Especially ones that make the brain a little happier and the clinical data a lot more interesting.
The study was published in The Lancet Psychiatry.
Read about how video games can also help in the treatment of depression.
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