What question did this study set out to answer?

This research aimed to determine if levodopa treatment during rehabilitation affects post-stroke depression in stroke patients.

February 19, 2026Open Access

The impact of levodopa on post-stroke depression: the ESTREL-depression-study

Key Result

Levodopa treatment during rehabilitation did not reduce post-stroke depression at 3 months (26% vs 28%; OR 0.93, 95% CI 0.60–1.43) compared to placebo.

Key Points

This research aimed to determine if levodopa treatment during rehabilitation affects post-stroke depression in stroke patients.
Multicenter, randomized, double-blind, placebo-controlled design.
Participants received either levodopa/carbidopa or placebo for 39 days during rehabilitation.
Only participants who completed at least 80% of their medication were included in the analysis.
Post-stroke depression was measured using T-scores three months after randomization.
407 participants were analyzed, with similar rates of post-stroke depression in both levodopa (26%) and placebo (28%) groups.
No significant difference in odds of post-stroke depression between groups (OR = 0.93, 95% CI 0.60–1.43).
Levodopa treatment did not yield any beneficial effects on the occurrence of post-stroke depression.

Structured PICO

Does levodopa/carbidopa reduce the occurrence of post-stroke depression in patients with acute ischemic or hemorrhagic stroke?

Population

407 participants with an acute ischemic or hemorrhagic stroke without a history of depression, who took at least 80% of the study medication, median age 72, 60% male.

Intervention

Levodopa/carbidopa (100/25 mg) three times daily for 39 days

Comparator

Placebo three times daily for 39 days

Outcome

Presence of post-stroke depression (defined as having a T-score of ≥55 in the Patient-Reported Outcomes Measurement Information System short-form depression-4a) 3 months after randomizationpatient reported

Levodopa/carbidopa treatment during in-hospital rehabilitation does not reduce the occurrence of post-stroke depression at 3 months compared to placebo.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Abstract Introduction Post-stroke depression (PSD) frequently occurs after acute stroke and negatively affects rehabilitation. Dopamine has beneficial effects on motivation and emotional stability. In stroke patients, low dopamine levels are linked to PSD. This study investigated whether levodopa treatment during in-hospital rehabilitation impacts PSD compared to placebo. Patients and methods ESTREL-Depression was a pre-planned analysis of the multicenter, randomized, double-blind, placebo-controlled ESTREL trial. Participants with an acute ischemic or hemorrhagic stroke were randomly assigned to receive either levodopa/carbidopa (100/25 mg) or placebo three times daily for 39 days. All ESTREL participants with (1) information about the presence or absence of depression at three months and (2) who took at least 80% of the study medication were eligible for the study. Participants with a history of depression were excluded. For the primary outcome, the presence of PSD was defined as having a T-score of ≥55 in the Patient-Reported Outcomes Measurement Information System short-form depression-4a 3 months after randomization. Binary logistic regression was performed to assess the effect of levodopa on PSD. Results The study included 407 ESTREL participants (median age 72, 60% male), 209 receiving levodopa, and 198 receiving placebo. At 3 months, the frequency and odds of PSD did not differ between the levodopa group (26%) and the placebo group (28%) (OR = 0.93, 95% CI, 0.60–1.43). Conclusion In the ESTREL-Depression study, treatment with levodopa had no impact on the occurrence of PSD. Clinical Trial Registration ClinicalTrials.gov: NCT03735901 (https://clinicaltrials.gov/study/NCT03735901).

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