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Clinician Article

Oxycodone for neuropathic pain in adults.



  • Gaskell H
  • Derry S
  • Stannard C
  • Moore RA
Cochrane Database Syst Rev. 2016 Jul 28;7(7):CD010692. doi: 10.1002/14651858.CD010692.pub3. (Review)
PMID: 27465317
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Disciplines
  • Endocrine
    Relevance - 6/7
    Newsworthiness - 5/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 4/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 4/7
  • Internal Medicine
    Relevance - 6/7
    Newsworthiness - 4/7
  • Special Interest - Pain -- Physician
    Relevance - 6/7
    Newsworthiness - 4/7
  • Neurology
    Relevance - 4/7
    Newsworthiness - 3/7

Abstract

BACKGROUND: This is an update of an earlier review that considered both neuropathic pain and fibromyalgia (Issue 6, 2014), which has now been split into separate reviews for the two conditions. This review considers neuropathic pain only.Opioid drugs, including oxycodone, are commonly used to treat neuropathic pain, and are considered effective by some professionals. Most reviews have examined all opioids together. This review sought evidence specifically for oxycodone, at any dose, and by any route of administration. Separate reviews consider other opioids.

OBJECTIVES: To assess the analgesic efficacy and adverse events of oxycodone for chronic neuropathic pain in adults.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE from inception to 6 November 2013 for the original review and from January 2013 to 21 December 2015 for this update. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. This update differs from the earlier review in that we have included studies using oxycodone in combination with naloxone, and oxycodone used as add-on treatment to stable, but inadequate, treatment with another class of drug.

SELECTION CRITERIA: We included randomised, double-blind studies of two weeks' duration or longer, comparing any dose or formulation of oxycodone with placebo or another active treatment in chronic neuropathic pain.

DATA COLLECTION AND ANALYSIS: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.

MAIN RESULTS: The updated searches identified one additional published study, and one clinical trial registry report. We included five studies reporting on 687 participants; 637 had painful diabetic neuropathy and 50 had postherpetic neuralgia. Two studies used a cross-over design and three used a parallel group design; all studies used a placebo comparator, although one study used an active placebo (benztropine). Modified-release oxycodone (oxycodone MR) was titrated to effect and tolerability. One study used a fixed dose combination of oxycodone MR and naloxone. Two studies added oxycodone therapy to ongoing, stable treatment with either pregabalin or gabapentin. All studies had one or more sources of potential major bias.No study reported the proportion of participants experiencing 'substantial benefit' (at least 50% pain relief or who were very much improved). Three studies (537 participants) in painful diabetic neuropathy reported outcomes equivalent to 'moderate benefit' (at least 30% pain relief or who were much or very much improved), which was experienced by 44% of participants with oxycodone and 27% with placebo (number needed to treat for one additional beneficial outcome (NNT) 5.7).All studies reported group mean pain scores at the end of treatment. Three studies reported a greater pain intensity reduction and better patient satisfaction with oxycodone MR alone than with placebo. There was a similar result in the study adding oxycodone MR to stable, ongoing gabapentin, but adding oxycodone MR plus naloxone to stable, ongoing pregabalin did not show any additional effect.More participants experienced adverse events with oxycodone MR alone (86%) than with placebo (63%); the number needed to treat for an additional harmful outcome (NNH) was 4.3. Serious adverse events (oxycodone 3.4%, placebo 7.0%) and adverse event withdrawals (oxycodone 11%, placebo 6.4%) were not significantly different between groups. Withdrawals due to lack of efficacy were less frequent with oxycodone MR (1.1%) than placebo (11%), with a number needed to treat to prevent one withdrawal of 10. The add-on studies reported similar results.We downgraded the quality of the evidence to very low for all outcomes, due to limitations in the study methods, heterogeneity in the pain condition and study methods, and sparse data.

AUTHORS' CONCLUSIONS: There was only very low quality evidence that oxycodone (as oxycodone MR) is of value in the treatment of painful diabetic neuropathy or postherpetic neuralgia. There was no evidence for other neuropathic pain conditions. Adverse events typical of opioids appeared to be common.


Clinical Comments

Endocrine

This is a review of this narcotic for diabetic painful neuropathy, but its efficacy seems limited. The study is likely more of interest to neurologists.

Endocrine

Re-enforces my own bias. All practitioners who see large numbers of Type 2 diabetes patients and the elderly who carry the diagnosis of neuropathic pain should be made aware of this. Well done review with cautious conclusions.

Family Medicine (FM)/General Practice (GP)

When our patients suffer from neuropathic pain and, with only modest efficacy of alternatives in the majority (tricyclics, meditation), any reduction of pain reported by patients as meaningful is powerful reinforcement to use narcotics at the lowest effective dose. If there were consistently better alternatives, we would use them!

Family Medicine (FM)/General Practice (GP)

As is typical of Cochrane reviews, this review was done well and seems to be clear of bias. It`s important to note: the finding that there is weak evidence for using opiates for neuropathic pain, is not the same as finding evidence that opiates are not effective.

General Internal Medicine-Primary Care(US)

The quality of the evidence is too low for any practitioner to make use of this updated Cochrane review. Given the public outcry around prescribing long-term narcotics to patients, I would be surprised if any clinician would consider prescribing long-acting narcotics for patients with painful diabetic neuropathy or postherpetic neuralgia as a first- or second-line agent.

General Internal Medicine-Primary Care(US)

More evidence is needed about the potential benefit (or lack of benefit) of narcotics in treating chronic pain syndromes - including diabetic and herpetic neuropathy.

Internal Medicine

There are other more evidence based effective medications that are useful for neuropathy. This article supports using them rather than oxycodone as first line.

Special Interest - Pain -- Physician

This article summaries the evidence for oxycodone, specifically for neuropathic pain, and finds there is only weak evidence for oxycodone use in neuropathic pain.

Special Interest - Pain -- Physician

Sadly, this paper largely shows that there are no good studies - either positive or negative - for this question. I would say there is little quality data and thus any conclusions about usefulness are uncertain.

Special Interest - Pain -- Physician

There is some arbitrariness to the threshold of efficacy that is being used to validate the conclusion reached in this review.

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