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

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.