A new study has found that levodopa, a medication commonly used to treat Parkinson’s disease, could offer new hope to people battling depression—especially those with high levels of inflammation.
Levodopa works by increasing dopamine, the brain chemical that helps regulate motivation, reward, and pleasure. And according to researchers at Emory University, this dopamine-boosting drug may be particularly effective for people whose depression comes with a side of high inflammation.
In fact, a simple and widely available blood test could help predict who’s most likely to benefit.
“We’re looking at a more personalized approach to treating depression,” says Jennifer C. Felger, lead investigator and associate professor of psychiatry and behavioral sciences at Emory’s School of Medicine. “Targeting dopamine in patients with higher inflammation may open up a new path forward.”
The study, published in Brain, Behavior & Immunity, focused on patients with elevated levels of C-reactive protein (CRP), a common marker of inflammation measured through routine bloodwork. Researchers found that participants with CRP levels above 2 mg/L responded significantly better to repeated doses of levodopa over one week.
Brain scans showed improved connectivity between two key parts of the brain’s reward system: the ventral striatum and the ventromedial prefrontal cortex. These areas are known to be disrupted in people suffering from low motivation and anhedonia—the inability to feel joy or pleasure.
Interestingly, the study also found that not all patients needed the same dosage. About half of the participants showed improvements with just 150 mg/day of levodopa, while the other half required higher doses—up to 450 mg/day—to experience the same benefits.
This is especially relevant because standard antidepressants often fall short for patients with inflammation-linked depression. In those cases, inflammation may suppress dopamine function, dulling the brain’s ability to process rewards and maintain motivation.
By boosting dopamine directly, levodopa appears to bypass this roadblock—restoring activity in reward circuits and offering relief from some of the most difficult symptoms of depression.
“These findings are a significant step forward in the personalized treatment of depression,” Felger says. “They show how something as simple as a blood test could help match patients with treatments that work better for them.”
The next step? A larger, eight-week clinical trial is underway to explore whether longer-term treatment with levodopa can further ease symptoms of depression and anhedonia in people with high CRP.
Funded by the National Institutes of Health, this research adds momentum to the growing movement toward precision psychiatry—where treatment is tailored to a person’s unique biology.
Original study DOI: 10.1016/j.bbi.2024.12.026
Source: Emory University
