Levodopa Fails to Enhance Motor Recovery After Acute Stroke: Study
A new study published in the Journal of American Medical Association showed that adding levodopa to normal inpatient rehabilitation did not substantially enhance motor function at 3 months, suggesting that levodopa is not beneficial for post-stroke motor recovery.
Levodopa may promote neuroplasticity and improve dopaminergic signaling, which may improve motor recovery following a stroke. Despite conflicting data on its efficacy, levodopa is utilized in stroke rehabilitation. Therefore, this study was to ascertain if levodopa, as opposed to a placebo, given in addition to standardized rehabilitation based on active task-oriented training, is linked to improved motor recovery in acute stroke patients.
13 stroke units and centers as well as 11 cooperating rehabilitation facilities in Switzerland participated in this study. 610 patients with acute ischemic or hemorrhagic stroke who had clinically significant hemiparesis (i.e., a total score of ≥3 points on the following National Institutes of Health Stroke Scale items: motor arm, motor leg, or limb ataxia) were randomized 1:1 to receive levodopa or placebo between June 14, 2019 (first patient, first visit) and August 27, 2024 (last patient, last visit). In addition to structured rehabilitation therapy based on active task-oriented training, patients received levodopa/carbidopa (100 mg/25 mg; n = 307) or placebo (n = 303) three times daily for 39 days.
582 (95.4%) of the 610 patients (median [IQR] age, 73 [64-82] years; 252 [41.3%] female; median baseline FMA total score, 34 [14-54]) were eligible for the primary analysis after 28 of them passed away within 3 months. The levodopa group's median (IQR) FMA total score at 3 months was 68 (42-85) points, whereas the placebo group's was 64 (44-83) points.
The levodopa and placebo groups' mean differences in the FMA total score were -0.90 points (95% CI, -3.78 to 1.98; P =.54). The most frequent adverse event was infection (levodopa, n = 55; placebo, n = 44). There were 126 severe adverse events in the levodopa group and 129 in the placebo group.
Overall, when compared to a placebo plus standardized therapy, levodopa added to standardized rehabilitation did not substantially enhance motor function at 3 months in individuals undergoing inpatient rehabilitation for acute stroke. The use of levodopa in addition to rehabilitation treatment to improve motor recovery following an acute stroke is not supported by these findings.
Reference:
Engelter, S. T., Kaufmann, J. E., Zietz, A., Luft, A. R., Polymeris, A., Altersberger, V. L., Wiesner, K., Wiegert, M., Held, J. P. O., Rottenberger, Y., Schwarz, A., Medlin, F., Accolla, E. A., Foucras, S., Kägi, G., De Marchis, G. M., Politz, S., Greulich, M., Tarnutzer, A. A., … ESTREL Investigators. (2025). Levodopa added to stroke rehabilitation: The ESTREL randomized clinical trial: The ESTREL randomized clinical trial. JAMA: The Journal of the American Medical Association, 334(17), 1523–1532. https://doi.org/10.1001/jama.2025.15185
