Subthalamic deep brain stimulation and levodopa in Parkinson’s disease: a meta-analysis of combined effects

Joaquin A. Vizcarra, Miguel Situ-Kcomt, Carlo Alberto Artusi, Andrew P. Duker, Leonardo Lopiano, Michael S. Okun, Alberto J. Espay, Aristide Merola

Research output: Contribution to journalReview articlepeer-review

37 Scopus citations


Introduction: While subthalamic nucleus deep brain stimulation (STN-DBS) and levodopa improve motor symptoms in Parkinson disease (PD) to a similar magnitude, their combined effect remains unclear. We sought to evaluate whether STN-DBS and levodopa yield differential effects on motor outcomes, dyskinesia, and activities of daily living (ADL) when combined compared to when administered alone. Methods: We conducted a meta-analysis of all studies reporting motor, dyskinesia, and ADL outcomes after bilateral STN-DBS in PD with presurgical Unified Parkinson’s Disease Rating Scale (UPDRS-III) in Medication-OFF and Medication-ON states and postsurgical assessments in four conditions: Stimulation-ON/Medication-ON, Stimulation-ON/Medication-OFF, Stimulation-OFF/Medication-ON, and Stimulation-OFF/Medication-OFF. Dyskinesia duration (UPDRS item 32) and ADL (UPDRS-II) were compared between high and low postsurgical levodopa equivalent daily dose (LEDD) reduction. Random-effects meta-analyses using generic-inverse variance were conducted. Confidence in outcomes effect sizes was assessed. Results: Twelve studies were included (n = 401 patients). Stimulation-ON/Medication-ON was associated with an UPDRS-III improvement of − 35.7 points [95% confidence interval, − 40.4, − 31.0] compared with Stimulation-OFF/Medication-OFF, − 11.2 points [− 14.0, − 8.4] compared with Stimulation-OFF/Medication-ON, and − 9.5 points [− 11.0, − 8.0] compared to Stimulation-ON/Medication-OFF within 5 years. The difference was maintained beyond 5 years by − 28.6 [− 32.8, − 24.4], − 8.1 [− 10.2, − 5.9], and − 8.0 [− 10.3, − 5.6], respectively. No difference was observed between Stimulation-ON/Medication-OFF and Stimulation-OFF/Medication-ON within and beyond 5 years. Dyskinesia duration and ADL outcomes were similar in high vs. low postsurgical LEDD reduction. Conclusion: Subthalamic nucleus deep brain stimulation and levodopa independently lessened motor severity in PD to a similar magnitude, but their combined effect was greater than either treatment alone, suggesting therapeutic synergism.

Original languageEnglish (US)
Pages (from-to)289-297
Number of pages9
JournalJournal of Neurology
Issue number2
StatePublished - Feb 1 2019
Externally publishedYes


  • Deep brain stimulation
  • Levodopa
  • Parkinson
  • Subthalamic nucleus
  • Synergism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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