ESTREL-Fatigue-association of levodopa with post-stroke fatigue.

Area of Science:

• Neurology
• Pharmacology
• Rehabilitation Medicine

Background:

• Post-stroke fatigue (PSF) is a prevalent condition significantly impacting stroke survivors' rehabilitation outcomes.
• Dopaminergic agents, such as levodopa, are being explored for their potential to alleviate PSF.

Purpose of the Study:

• To investigate the efficacy of levodopa in reducing the frequency and severity of post-stroke fatigue (PSF) during in-hospital rehabilitation.
• To compare levodopa treatment against a placebo in patients experiencing acute stroke.

Main Methods:

• An exploratory analysis of the multicentre, randomised, placebo-controlled ESTREL trial (ESTREL-Fatigue) was conducted.
• Participants receiving levodopa (100 mg/carbidopa 25 mg) or placebo three times daily for 39 days were included if they reported fatigue at 5 weeks and adhered to medication.
• The primary endpoint was the presence of PSF at 5 weeks (PROMIS Fatigue-Short-form-4a T-score ≥ 55), with secondary endpoints using T-score cutoffs of ≥ 60 and ≥ 70.

Main Results:

• Of 456 participants (90.3%), 26.8% in the levodopa group and 29.4% in the placebo group reported PSF at 5 weeks (OR: 0.88; 95% CI, 0.58-1.32).
• Analyses for moderate (T-score ≥ 60) and severe (T-score ≥ 70) fatigue showed no significant differences between groups (ORs 0.78 and 0.8, respectively).
• Sensitivity analyses, including intention-to-treat and mixed-effects logistic regression, confirmed no significant difference in PSF between levodopa and placebo groups.

Conclusions:

• Levodopa treatment was not associated with a reduction in post-stroke fatigue (PSF) compared to placebo during in-hospital rehabilitation.
• The findings suggest that levodopa, under the conditions studied, does not offer a significant benefit for managing PSF in acute stroke patients.