Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson’s disease: a meta-analysis

Abstract

Background

Selegiline or levodopa treatment has been suggested as a therapeutic method for Parkinson’s disease (PD) in many clinical trial reports. However, the combined effects of two drugs still remain controversial. The aim of this report was to evaluate the clinical efficacy and safety of selegiline plus levodopa (S + L) combination therapy in the treatment of PD compared to that of L monotherapy, to provide a reference resource for rational drug use.

Methods

Randomized controlled trials (RCTs) of S + L for PD published up to September, 2018 were searched. Mean difference (MD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Sensitivity analysis was also performed. The outcomes measured were as follows: the unified Parkinson’s disease rating scale (UPDRS) scores, modified Webster score, adverse events and mortality.

Results

Fourteen RCTs with 2008 participants were included. Compared with L monotherapy, the pooled effects of S + L combination therapy on UPDRS score were (eleven trials; MD − 7.00, 95% CI − 8.35 to − 5.65, P < 0.00001) for total UPDRS score (nine trials; MD − 5.74, 95% CI − 7.71 to − 3.77, P < 0.00001) for motor UPDRS score (seven trials; MD − 1.61, 95% CI − 2.18 to − 1.04, P < 0.00001) for activities of daily living UPDRS score (three trials; MD − 0.38, 95% CI − 0.61 to − 0.14, P = 0.002) for mental UPDRS score. The Webster score showed significant decrease in the S + L combination therapy compared to L monotherapy (four trials; MD − 5.71, 95% CI − 7.11 to − 4.32, P < 0.00001). Compared with L monotherapy, S + L combination therapy did not increase the number of any adverse events significantly in PD patients (ten trials; OR 1.58, 95% CI 0.83–3.00, P = 0.16).

Conclusions

S + L combination therapy is superior to L monotherapy for the improvement of clinical symptoms in PD patients. Moreover, the safety profile of S + L combination therapy is comparable with that of L monotherapy.

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Funding

This study was supported by grants from the Natural Science Foundation of Guangxi Zhuang Autonomous Region of China (No. 2018GXNSFAA050002), the National Natural Science Foundation of China (No. 31860228), the Key projects of Natural Science Foundation of the Guangxi Zhuang Autonomous Region (2018GXNSFDA281007) and the Doctoral Scientific Research Foundation of Yulin Normal University of China (No. G20160006).

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DQJ formulated the research question, designed the study and screened the articles, collected the data, assessed the quality of studies and drafted the manuscript. MXL screened the articles. LLJ collected the data and analyzed the data. XBC assessed the qualities of studies and revised the manuscript. XWZ assisted with formulating the research question and supervising the quality of the paper.

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Correspondence to Xing-Wen Zhou.

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Jiang, D., Li, M., Jiang, L. et al. Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson’s disease: a meta-analysis. Aging Clin Exp Res 32, 769–779 (2020). https://doi.org/10.1007/s40520-019-01232-4

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Keywords

  • Parkinson’s disease
  • Selegiline
  • Levodopa
  • UPDRS
  • Safety
  • Meta-analysis