Objective: To compare the clinical effectiveness between continuous dopaminergic stimulation (CDS)-based and intermittent levodopa (IL) treatment in patients with early to mid-stage Parkinson’s disease (PD).

Background: Extended oral levodopa administration leads to motor complications such as wearing-off phenomenon and dyskinesia. The relevant randomized controlled trials (RCTs) have shown CDS-based treatment to be more effective than IL treatment, however, no systematic review and meta-analysis was performed specifically to access the outcomes. Consequently, RCTs need to be summarized and analyzed to generated more robust evidence.

Method: This study was registered in PROSPERO (CRD42024501692). PubMed, Embase, Web of Science, Cochrane Central Register, and ClinicalTrials.gov databases were systematically searched for studies published until December 2023. MDS-UPDRS Ⅱ and Ⅲ were the primary endpoints, whereas good on-time and off-time were the secondary endpoints. Statistical analyses were performed by Review Manager 5.4. The mean difference (MD) with the 95% confidence interval (CI) was used as the measure of continuous variables. Heterogeneity was quantified by the I² statistic.

Results: The pooled outcomes of 5 RCTs, including 1294 patients (605 in CDS and 689 in IL), showed significant decrease of MDS-UPDRS Ⅱ in CDS-based vs. IL treatment at 6 months (MD = -0.63; 95% CI: -1.20, -0.07; I² = 32%) and 12 months (MD = -0.69; 95% CI: -1.21, -0.18; I² = 21%). The pooled mean difference of MDS-UPDRS III in 8 RCTs, involving 988 patients (501 in CDS and 487 in IL), indicated a significant reduction in CDS-based vs. IL treatment (MD = -1.02; 95% CI: -1.97, -0.07; I² = 0%). Good on-time data, available in 3 studies, containing 916 patients (464 in CDS and 452 in IL), revealed improvement in CDS-based vs. IL treatment (MD = 0.63 hr/d; 95% CI: 0.35, 0.91; I² = 40%). The estimated outcome of off- time, obtained from 3 studies, comprising 916 patients (464 in CDS and 452 in IL), found a decline in CDS-based vs. IL treatment (MD = -0.6 hr/d; 95% CI: -1.03, -0.18; I² = 71%).

Conclusion: Continuous dopaminergic stimulation-based levodopa treatment significantly improved activities of daily living, motor functions and wearing-off in comparison to intermittent levodopa treatment for patients with early to mid-stage PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/continuous-dopaminergic-stimulation-based-levodopa-treatment-in-early-to-mid-stage-parkinsons-disease-patients-a-systematic-review-and-meta-analysis/