Cochrane Database Syst Rev. 2026 Oct 29;10:CD013416. doi: 10.1002/14651858.CD013416.pub2.
ABSTRACT
RATIONALE: Stroke is a leading cause of mortality and disability worldwide. There is a lack of evidence regarding pharmacological enhancement of stroke recovery with dopamine agonists or levodopa, in particular in terms of motor deficits.
OBJECTIVES: To assess the effects of dopaminergic agents, defined as levodopa or dopamine agonists, on improving motor function after stroke.
SEARCH METHODS: We conducted an extensive database search on the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, Science Citation Index Expanded, CPCI-S, BIOSIS Citation Index, ProQuest Dissertation and Theses Global up to November 2025.
ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) that enrolled participants with a clinical diagnosis of stroke, irrespective of age or stroke aetiology and without a pre-existing indication for the use of levodopa or dopamine agonists. Eligible trials compared levodopa or dopamine agonists with a comparator group who received placebo or no medication, with equivalent rehabilitative care in both groups, and aimed at enhancing motor function after stroke.
OUTCOMES: Motor function was the critical benefit outcome. As a critical harm outcome, we assessed serious adverse events. Important outcomes consisted of death, recurrent stroke, disability, dependence, health-related quality of life, activities of daily living, total number of adverse events, and psychiatric adverse events.
RISK OF BIAS: Two review authors independently assessed the risk of bias for each trial using the Cochrane Risk of bias tool (RoB 1).
SYNTHESIS METHODS: We synthesised results for each outcome using a standardised mean difference (SMD) or mean difference (MD) for continuous data and risk ratio (RR) for dichotomous results, with a random-effects model due to heterogeneity between the trials. For non-extractable trials due to missing numerical data, we synthesised the results narratively. We used GRADE to assess the certainty of evidence for each outcome.
INCLUDED STUDIES: We included 12 parallel-group RCTs involving 1860 participants. The trials were conducted in Europe, the USA and Asia, and were published between 2001 and 2025. All trials included participants with either ischaemic strokes only or both haemorrhagic and ischaemic strokes. The mean age of all included participants ranged from 55 to 78 years. Of the included trials, 10 were placebo-controlled and two compared levodopa or dopamine agonists against usual care. Eleven trials investigated levodopa as the intervention and one examined the dopamine agonist ropinirole.
SYNTHESIS OF RESULTS: Across 12 included trials, complete data on motor function were available for six trials with continuous data (1258 participants) and for two trials with dichotomous data (615 participants), of which one trial assessed both continuous and dichotomous data. We detected no difference in motor function scores between levodopa or dopamine agonists and the comparator groups for continuous outcomes (SMD 1.42, 95% confidence interval (CI) -0.20 to 3.05; 6 trials, 1258 participants; very low-certainty evidence). The wide confidence intervals indicate substantial imprecision in the effect estimate. Consistent with those results, we detected no difference for dichotomous motor function outcomes either (RR 0.93, 95% CI 0.82 to 1.06; 2 trials, 615 participants; anticipated absolute event rate of having a favourable outcome of 581/1000 in the comparator group versus 540/1000 with levodopa/dopamine agonists; low-certainty evidence). Heterogeneity for the critical outcome motor function (continuously measured) was high (I2 = 99%). However, a sensitivity analysis including only two trials with a low risk of bias in all domains, that accounted for the majority of the included patient population (1025 of 1258), showed no heterogeneity (I2 = 0%), and a smaller confidence interval (SMD 0.02, 95% CI -0.10 to 0.14; 2 trials, 1025 participants), implying no difference between groups. Six trials assessed serious adverse events, including 1281 participants. There was no notable difference in the risk of serious adverse events between groups (RR 1.03, 95% CI 0.83 to 1.27; anticipated absolute event rate of 302/1000 events in comparators versus 311/1000 events with levodopa/dopamine agonists; low-certainty evidence). All important outcomes showed no notable between-group differences. The certainty of evidence, according to GRADE, was very low for continuously measured scores of motor function, low for dichotomous motor function outcomes, and low for serious adverse events. Together with heterogeneity in both interventions and outcomes, inconsistency of findings, imprecision related to small sample sizes in some trials, and imprecision of summary effect, there are major limitations of the current evidence.
AUTHORS' CONCLUSIONS: Based on limited data, we did not find evidence that the use of levodopa or dopamine agonists improves motor function after a stroke. Given the low certainty of evidence due to limited data, wide confidence intervals, and heterogeneity across trials, further research may change this assessment and explore whether effects are different in specific subgroups of patients.
FUNDING: Science funds [Wissenschaftsfonds] Department of Rehabilitation and Neurology, University Department of Geriatric Medicine, Felix Platter, University of Basel, Switzerland. This review had no external funding.
REGISTRATION: Protocol available via https://doi.org/10.1002/14651858.CD013416.
PMID:42954433 | DOI:10.1002/14651858.CD013416.pub2