JournalCochrane Database of Systematic Reviews
BACKGROUND: This review is one of a series on drugs used to treat neuropathic pain and fibromyalgia. These conditions are estimated to affect 3 to 10% of adults, and are difficult to treat. Although they probably have different aetiologies, neuropathic pain and fibromyalgia can respond to the same therapies. There have been substantial changes in the standards of evidence considered necessary for assessment of interventions to treat chronic pain, to provide data that are more robust and clinically relevant. Oxycodone is a strong opioid agonist widely used to manage severe pain; this review assesses evidence for oxycodone using current standards of evidence designed to reduce bias.
OBJECTIVES: To assess the analgesic efficacy and adverse events of oxycodone for chronic neuropathic pain and fibromyalgia.
SEARCH METHODS: On 6 November 2013, we searched CENTRAL, MEDLINE and EMBASE databases. We reviewed the bibliographies of all included studies and of reviews, and also searched two clinical trial databases, ClinicalTrials.gov and the World Health Organisation (WHO) International Clinical Trials Registry Platform, to identify additional published or unpublished data.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) with double-blind assessment of participant outcomes following two weeks of treatment or longer (although the emphasis of the review was on studies of eight weeks or longer) that used a placebo or active comparator.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted efficacy and adverse event data, examined issues of study quality, and assessed risk of bias. We performed analysis using three tiers of evidence. First tier evidence was derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, eight to 12 weeks duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that was considered very likely to be biased or used outcomes of limited clinical utility, or both.
MAIN RESULTS: We included three studies with 254 participants; 204 had painful diabetic neuropathy and 50 postherpetic neuralgia. Study size ranged from 45 to 159 participants. Two studies used a cross-over design and one a parallel group design; study duration was four or six weeks. Controlled release oxycodone (oxycodone CR) was used in all three studies, with doses titrated up to a maximum of between 60 and 120 mg daily; mean doses achieved ranged between 37 and 45 mg daily. All studies used a placebo comparator, although in one study, an active placebo (benztropine) was used. All studies had one or more sources of potential major bias.
No study reported the proportion of participants experiencing at least 50% pain relief or who were very much improved, while one reported the proportion with at least 30% pain relief, two reported at least moderate pain relief, and one reported the number of participants who considered treatment to be moderately effective. No study provided first or second tier evidence for an efficacy outcome. Third tier evidence indicated greater pain intensity reduction and better patient satisfaction with oxycodone than with placebo in all three studies, but such evidence was derived mainly from group mean data, with last observation carried forward (LOCF) imputation or completer analysis, in small studies lasting less than eight weeks (very low quality evidence).
Adverse events were more common with oxycodone CR than with placebo. At least one adverse event was experienced by 86% of participants taking oxycodone CR and 63% taking placebo, and the number needed to treat for an additional harmful effect (NNH) was 4.3. The effect of oxycodone on serious adverse events reported was uncertain in comparison with placebo (oxycodone 3.4% versus placebo: 7.0%; RR 0.48 (95% confidence interval (CI) 0.18 to 1.23; very low quality evidence); one death was reported with oxycodone CR, but was not attributed to treatment. Adverse event withdrawals did not differ significantly between groups, occurring in 11% of participants with oxycodone CR and 6.4% with placebo (RR 1.69 (0.83 to 3.43); very low quality evidence). Withdrawals due to lack of efficacy were less frequent with oxycodone CR (1.1%) than placebo (11%), with an NNT to prevent one withdrawal of 10 (RR 0.12 (0.03 to 0.45); very low quality evidence).
We found no relevant studies in chronic neuropathic pain conditions other than painful diabetic neuropathy or postherpetic neuralgia, or in fibromyalgia.
AUTHORS' CONCLUSIONS: No convincing, unbiased evidence suggests that oxycodone (as oxycodone CR) is of value in treating people with painful diabetic neuropathy or postherpetic neuralgia. There is no evidence at all for other neuropathic pain conditions, or for fibromyalgia. Adverse events typical of opioids appear to be common.
Copyright © 2014 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Epistemonikos ID: ada510f127da719c43ae020230eedee94d27afea
First added on: Jul 24, 2014