Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults Stable (no update expected for reasons given in 'What's new')

Abstract

Background

Paracetamol, either alone or in combination with codeine or dihydrocodeine, is commonly used to treat chronic neuropathic pain. This review sought evidence for efficacy and harm from randomised double‐blind studies.

Objectives

To assess the analgesic efficacy and adverse events of paracetamol with or without codeine or dihydrocodeine for chronic neuropathic pain in adults.

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from inception to July 2016, together with reference lists of retrieved papers and reviews, and two online study registries.

Selection criteria

We included randomised, double‐blind studies of two weeks' duration or longer, comparing paracetamol, alone or in combination with codeine or dihydrocodeine, 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. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE.

Main results

No study satisfied the inclusion criteria. Effects of interventions were not assessed as there were no included studies. We have only very low quality evidence and have no reliable indication of the likely effect.

Authors' conclusions

There is insufficient evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

Author(s)

Philip J Wiffen, Roger Knaggs, Sheena Derry, Peter Cole, Tudor Phillips, R Andrew Moore

Abstract

Plain language summary

Paracetamol (acetaminophen) alone, or in combination with codeine or dihydrocodeine, for neuropathic pain in adults 

Bottom line 

There is no good evidence to support or refute the suggestion that paracetamol alone, or in combination with codeine or dihydrocodeine, works in any neuropathic pain condition.

Background 

Neuropathic pain is pain coming from damaged nerves. It is different from pain messages that are carried along healthy nerves from damaged tissue (e.g. a fall or cut, or arthritic knee). Neuropathic pain is often treated by different medicines (drugs) to those used for pain from damaged tissue, which we often think of as painkillers. Medicines that are sometimes used to treat depression or epilepsy (fits) can be very effective in some people with neuropathic pain. But sometimes paracetamol is used to treat neuropathic pain, either by itself or with the opioid painkillers codeine or dihydrocodeine.

Paracetamol has been widely available for over 50 years. There is evidence it works as a painkiller in some short‐lived pains, but it does not appear to work well for long lasting pains. We do not really know how it works. Paracetamol is commonly used combined with opioid drugs.

Opioid painkillers are drugs like morphine. Morphine is derived from plants, but many opioids are also made in a laboratory rather than being extracted from plants. Codeine and dihydrocodeine are often combined with paracetamol.

Study characteristics 

In July 2016, we searched for clinical trials where paracetamol alone, or in combination with codeine or dihydrocodeine, was used to treat neuropathic pain in adults. We found no studies that met our requirements for the review.

Key results 

Because there were no studies that could answer the questions in a reliable way, we cannot say whether paracetamol alone, or in combination with codeine or dihydrocodeine, works for chronic neuropathic pain.

Quality of the evidence 

We rated the quality of the evidence as very low because there were no studies. Very low quality evidence means that we are very uncertain about the impact of paracetamol alone, or in combination with codeine or dihydrocodeine, in any neuropathic pain condition.

Author(s)

Philip J Wiffen, Roger Knaggs, Sheena Derry, Peter Cole, Tudor Phillips, R Andrew Moore

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

For people with neuropathic pain

There is insufficient evidence to support or refute the suggestion that paracetamol, alone or in combination with codeine or dihydrocodeine, has any efficacy in any neuropathic pain condition.

For clinicians

There is insufficient evidence to support or refute the suggestion that paracetamol, alone or in combination with codeine or dihydrocodeine, has any efficacy in any neuropathic pain condition.

For policy makers

There is insufficient evidence to support or refute the suggestion that paracetamol, alone or in combination with codeine or dihydrocodeine, has any efficacy in any neuropathic pain condition. It should be noted that there is evidence of lack of effect of paracetamol alone in other chronic pain conditions. In the absence of any supporting evidence, these drugs should probably not be recommended, except at the discretion of a pain specialist.

For funders

There is insufficient evidence to support or refute the suggestion that paracetamol, alone or in combination with codeine or dihydrocodeine, has any efficacy in any neuropathic pain condition. It should be noted that there is evidence of lack of effect of paracetamol alone in other chronic pain conditions.

Implications for research 

Large, robust randomised trials with patient‐centred outcomes would be required to produce evidence to support or refute efficacy of paracetamol, alone or in combination with codeine or dihydrocodeine, in neuropathic pain. The necessary design of such trials is well established, but, for opioids in neuropathic pain, the outcomes should be those of at least 30% and at least 50% pain intensity reduction over baseline at the end of a trial of 12 weeks' duration in participants continuing on treatment. Withdrawal for any reason should be regarded as treatment failure, and last observation carried forward (LOCF) analysis should not be used. This is because, in chronic pain, opioids frequently produce withdrawal rates of 50% or more, meaning that LOCF analysis can overstate treatment efficacy to a large extent.

Given the knowledge that paracetamol is proven to be without effect or has no evidence to support efficacy in any chronic pain condition, the value of such trials would be questionable.

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