Prolonged-release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients

Eur J Pain. 2008 Aug;12(6):804-13. doi: 10.1016/j.ejpain.2007.12.010. Epub 2008 Feb 8.

Abstract

Background: Neuropathic pain remains one of the most challenging pain syndromes; under-diagnosed, poorly managed and associated with significant co-morbidity. With standard therapeutic treatments, responders rarely exceed 50% pain relief and the majority suffer from residual pain. Titration to optimum dose is often limited by dose-related adverse events.

Aims: This randomized, double-blind, placebo-controlled study assessed the potential benefit of adding oxycodone (OxyContin tablets) to gabapentin. The primary endpoint was to evaluate the analgesic efficacy of co-administration of gabapentin and prolonged-release oxycodone, whilst also evaluating the use of escape medication, sleep quality and global assessment of pain.

Methods: Three hundred and thirty eight patients with moderate to severe painful diabetic neuropathy despite receiving their maximum tolerated dose of gabapentin, had oral prolonged-release oxycodone or placebo tablets added to their therapy for up to 12 weeks.

Results: Oxycodone-gabapentin reduced pain score by 33% from baseline to end of treatment. The overall treatment effect was greater with oxycodone-gabapentin than with placebo-gabapentin (P = 0.007). Oxycodone-gabapentin also significantly improved pain relief vs gabapentin alone (P = 0.003). Oxycodone-gabapentin co-administration was associated with less escape medication use (P = 0.03) and fewer nights of disturbed sleep (P < 0.05). Discontinuations due to lack of therapeutic effect were much lower (14% vs 54%) with oxycodone-gabapentin. The commonly seen opiate-induced adverse events were not exacerbated by the combination of oxycodone and gabapentin.

Conclusions: This study provides the first evidence that co-administration of prolonged-release oxycodone and existing gabapentin therapy has a clinically meaningful effect in painful diabetic neuropathy.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Amines / administration & dosage*
  • Amines / adverse effects
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Calcium Channel Blockers / administration & dosage*
  • Calcium Channel Blockers / adverse effects
  • Cyclohexanecarboxylic Acids / administration & dosage*
  • Cyclohexanecarboxylic Acids / adverse effects
  • Delayed-Action Preparations
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / drug therapy*
  • Drug Synergism
  • Female
  • Gabapentin
  • Humans
  • Male
  • Middle Aged
  • Oxycodone / administration & dosage*
  • Oxycodone / adverse effects
  • Pain Measurement
  • Patient Satisfaction
  • Sleep Wake Disorders / etiology
  • Treatment Outcome
  • gamma-Aminobutyric Acid / administration & dosage*
  • gamma-Aminobutyric Acid / adverse effects

Substances

  • Amines
  • Analgesics, Opioid
  • Calcium Channel Blockers
  • Cyclohexanecarboxylic Acids
  • Delayed-Action Preparations
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Oxycodone