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

Plain-language summary: 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. 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. 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.