Hydromorphone for neuropathic pain in adults

Bottom line

There is no good evidence to support or refute the suggestion that hydromorphone 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 (for example, 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 can be very effective in some people with neuropathic pain. But sometimes opioid painkillers are used to treat neuropathic pain.

Opioid painkillers are drugs like morphine. Morphine is derived from plants, but many opioids are also made by chemical synthesis rather than being extracted from plants. Hydromorphone is one of these synthetic opioids. It is available in numerous countries for use as a painkiller, and can be given by mouth or by injection.

This review is part of an update of a previous review, Hydromorphone for acute and chronic pain that was withdrawn in 2013 because it needed updating and splitting to be more specific for different pain conditions. This review focuses only on neuropathic pain.

Study characteristics

In November 2015, we searched for clinical trials where hydromorphone was used to treat neuropathic pain in adults. We found one small study that did this and met our requirements for the review. The study had a complicated design. Only a minority of participants had neuropathic pain, with only 94 in the comparison with placebo. Important pain outcomes were not reported.

Key results

The study provided no convincing evidence of any benefit for hydromorphone over placebo. Of those people who started taking hydromorphone, one in eight stopped because of side effects in the first part of the study. The most common side effects were constipation and nausea, which are typically experienced with opioids.

Quality of the evidence

We rated the quality of the evidence as very low because of the study design, poor reporting of important outcomes, and small numbers of participants. Very low quality evidence means that we are very uncertain about the results.

Authors' conclusions: 

There was insufficient evidence to support or refute the suggestion that hydromorphone has any efficacy in any neuropathic pain condition.

Read the full abstract...
Background: 

Opioid drugs, including hydromorphone, 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 hydromorphone, at any dose, and by any route of administration. Other opioids are considered in separate reviews.

This review is part of an update of a previous review, Hydromorphone for acute and chronic pain that was withdrawn in 2013 because it needed updating and splitting to be more specific for different pain conditions. This review focuses only on neuropathic pain.

Objectives: 

To assess the analgesic efficacy of hydromorphone for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), via the CRSO; MEDLINE via Ovid; and EMBASE via Ovid from inception to 17 November 2015, 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 hydromorphone (at any dose, by any route of administration, or in any formulation) 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. We did not carry out any pooled analyses. We assessed the quality of the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation).

Main results: 

Searches identified seven publications relating to four studies. We excluded three studies. One post hoc (secondary) analysis of a study published in four reports assessed the efficacy of hydromorphone in neuropathic pain, satisfied our inclusion criteria, and was included in the review. The single included study had an enriched enrolment, randomised withdrawal design with 94 participants who were successfully switched from oral morphine to oral hydromorphone extended release (about 60% of those enrolled). These participants were then randomised to continuing hydromorphone for 12 weeks or tapering down the hydromorphone dose to placebo. The methodological quality of the study was generally good, but we judged the risk of bias for incomplete outcome data as unclear, and for study size as high.

Since we identified only one study for inclusion, we were unable to carry out any analyses. The included study did not report any of our prespecified primary outcomes, which relate to the number of participants achieving moderate or substantial levels of pain relief. It did report a slightly larger increase in average pain intensity for placebo in the randomised withdrawal phase than for continuing with hydromorphone. It also reported the number of participants who withdrew due to lack of efficacy in the randomised withdrawal phase, which may be an indicator of efficacy. However, in addition to using an enriched enrolment, randomised withdrawal study design, there was an unusual choice of imputation methods for withdrawals (about 50% of participants); the evidence was of very low quality and inadequate to make a judgement on efficacy. Adverse events occurred in about half of participants with hydromorphone, the most common being constipation and nausea. A similar proportion of participants experienced adverse events with placebo, the most common being opioid withdrawal syndrome (very low quality evidence). Most adverse events were mild or moderate in intensity. One in eight participants withdrew while taking hydromorphone during the conversion and titration phase, despite participants being opioid-tolerant (very low quality evidence).

We downgraded the quality of the evidence to very low because there was only one study with few participants, it did not report clinically useful efficacy outcomes, and it was a post hoc analysis.

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