title: Hydromorphone for neuropathic pain in adults.
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reviews.This review is part of an update of a previous review, Hydromorphone for acute and chronic pain that was withdrawn in 2013 because it needed updating and splitting to be more specific for different pain conditions.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.
  
  
  OBJECTIVE
  To assess the analgesic efficacy of hydromorphone for chronic neuropathic pain in adults, and the adverse events associated with its use in clinical trials.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  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.
  
  
  CONCLUSIONS
  There was insufficient evidence to support or refute the suggestion that hydromorphone has any efficacy in any neuropathic pain condition.
authors.affiliation: Pain Clinic, Macmillan Centre, Frenchay Hospital, Bristol, UK, BS16 1LE.
authors.forename: Cathy
authors.initials: C
authors.lastname: Stannard
authors.forename: Helen
authors.initials: H
authors.lastname: Gaskell
authors.forename: Sheena
authors.initials: S
authors.lastname: Derry
authors.forename: Dominic
authors.initials: D
authors.lastname: Aldington
authors.forename: Peter
authors.initials: P
authors.lastname: Cole
authors.forename: Tess E
authors.initials: TE
authors.lastname: Cooper
authors.forename: Roger
authors.initials: R
authors.lastname: Knaggs
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Wiffen
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Moore
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D059350:Chronic Pain / Q000188:drug therapy*; D006801:Humans; D004091:Hydromorphone / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000701:Analgesics, Opioid; D004091:Hydromorphone