Oxycodone or Higher Dose of Levodopa for the Treatment of Parkinsonian Central Pain: OXYDOPA Trial

Mov Disord. 2024 Sep;39(9):1533-1543. doi: 10.1002/mds.29878. Epub 2024 Jun 8.

Abstract

Background: Among the different types of pain related to Parkinson's disease (PD), parkinsonian central pain (PCP) is the most disabling.

Objectives: We investigated the analgesic efficacy of two therapeutic strategies (opioid with oxycodone- prolonged-release (PR) and higher dose of levodopa/benserazide) compared with placebo in patients with PCP.

Methods: OXYDOPA was a randomized, double-blind, double-dummy, placebo-controlled, multicenter parallel-group trial run at 15 centers within the French NS-Park network. PD patients with PCP (≥30 on the Visual Analogue Scale [VAS]) were randomly assigned to receive oxycodone-PR (up to 40 mg/day), levodopa/benserazide (up to 200 mg/day) or matching placebo three times a day (tid) for 8 weeks at a stable dose, in add-on to their current dopaminergic therapy. The primary endpoint was the change in average pain intensity over the previous week rated on VAS from baseline to week-10 based on modified intention-to-treat analyses.

Results: Between May 2016 and August 2020, 66 patients were randomized to oxycodone-PR (n = 23), levodopa/benserazide (n = 20) or placebo (n = 23). The mean change in pain intensity was -17 ± 18.5 on oxycodone-PR, -8.3 ± 11.1 on levodopa/benserazide, and -14.3 ± 18.9 in the placebo groups. The absolute difference versus placebo was -1.54 (97.5% confidence interval [CI], -17.0 to 13.90; P = 0.8) on oxycodone-PR and +7.79 (97.5% CI, -4.99 to 20.58; P = 0.2) on levodopa/benserazide. Similar proportions of patients in each group experienced all-cause adverse events. Those leading to study discontinuation were most frequently observed with oxycodone-PR (39%) than levodopa/benserazide (5%) or placebo (15%).

Conclusions: The present trial failed to demonstrate the superiority of oxycodone-PR or a higher dose of levodopa in patients with PCP, while oxycodone-PR was poorly tolerated. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; levodopa; oxycodone; pain; parkinsonian central pain.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use
  • Antiparkinson Agents* / administration & dosage
  • Antiparkinson Agents* / therapeutic use
  • Benserazide* / administration & dosage
  • Benserazide* / therapeutic use
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Humans
  • Levodopa* / administration & dosage
  • Levodopa* / therapeutic use
  • Male
  • Middle Aged
  • Oxycodone* / administration & dosage
  • Oxycodone* / therapeutic use
  • Pain Measurement
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy
  • Treatment Outcome

Substances

  • Oxycodone
  • Levodopa
  • Benserazide
  • Antiparkinson Agents
  • Analgesics, Opioid
  • benserazide, levodopa drug combination
  • Drug Combinations