Levodopa-Based Therapy in Stroke Rehabilitation: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background The dopaminergic system plays a key role in neuroplasticity and motor learning, suggesting that levodopa can enhance recovery after stroke. However, the clinical evidence is inconsistent. This systematic review and meta-analysis aimed to provide a definitive synthesis of randomized controlled trials (RCTs) that evaluated levodopa-based therapy as an adjunct to stroke rehabilitation. Methods Following PRISMA and Cochrane guidelines, we systematically searched PubMed, Embase, and CENTRAL from inception to October 2025 for RCTs comparing levodopa with placebo in adults who had experienced a stroke and were undergoing rehabilitation. The primary outcome was motor recovery, which was assessed using validated scales (eg, Fugl–Meyer Assessment). Secondary outcomes included mood and cognitive function. Pooled standardized mean differences (SMDs) were calculated using a random-effects model with the Hartung–Knapp–Sidik–Jonkman adjustment. Results Seven RCTs comprising 1257 participants (mean age, 62-73 years) met the inclusion criteria. Levodopa had no significant effect on motor function compared with placebo (SMD: 0.01; 95% CI: −0.10 to 0.13; I 2 = 0%), mood (SMD: −0.10; 95% CI: −0.30 to 0.10; I 2 = 3%), or cognition (SMD: −0.05; 95% CI: −0.29 to 0.19; I 2 = 0%). Sensitivity analyses confirmed the stability of the results. Conclusions Levodopa-based therapy does not improve motor, cognitive, or mood outcomes during stroke rehabilitation. These findings close a long-standing question and indicate that dopaminergic augmentation should not be used routinely outside of mechanistic or biomarker-stratified trials.