[Opioids in chronic neuropathic pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration]

Schmerz. 2015 Feb;29(1):35-46. doi: 10.1007/s00482-014-1455-x.
[Article in German]


Background: The efficacy and safety of opioid therapy in chronic neuropathic pain (CNP) is under debate. We updated a recent Cochrane systematic review on the efficacy, tolerability and safety of opioids in CNP.

Methods: We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as the reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in CNP. We included double-blind randomized placebo-controlled studies of at least 4 weeks duration. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables.

Results: We included 12 RCTs with 1192 participants. The included diagnostic entities were painful diabetic neuropathy (four studies), postherpetic neuralgia (three studies), mixed polyneuropathic pain (two studies), and lumbar root, spinal cord injury and postamputation pain (one study each). Mean study duration was 6 (4-12) weeks. Four studies tested morphine, three studies tramadol, two studies oxycodone and one study tapentadol. These are the pooled results of studies with a parallel or cross-over design: opioids were superior to placebo in reducing pain intensity (SMD - 0.64 [95 % confidence interval, CI - 0.81, - 0.46], p < 0.0001; 11 studies with 1040 participants). Opioids were not superior to placebo in 50 % pain reduction (RD 0.16 [95 % CI - 0.04, 0.35], p = 0.11; one study with 93 participants). Opioids were not superior to placebo in reports of much or very much improved pain (RD 0.17 [95 % CI - 0.01, 0.36], p = 0.07; one study with 53 participants). Opioids were superior to placebo in improving physical functioning (SMD - 0.28 [95 % CI - 0.43, - 0.13], p < 0.0001; seven studies with 680 participants). Patients dropped out less frequently due to lack of efficacy with opioids than with placebo (RD - 0.07 [95 % CI - 0.13, - 0.02], p = 0.008; six studies with 656 participants). Patients dropped out due to adverse events more frequently with opioids than with placebo (RD 0.08 [95 % CI 0.05, 0.12], p < 0.0001; ten studies with 1018 participants; number needed to harm 11 [95 % CI 8-17]). There was no significant difference between opioids and placebo in terms of the frequency of serious adverse events (SAE) or deaths.

Conclusion: In short-term studies (4-12 weeks) in CNP, opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. Opioids and placebo did not differ in terms of safety. The conclusion relating to the safety of opioids compared to placebo in CNP is limited by the low number of SAE and deaths. Short-term opioid therapy may be considered in selected CNP patients. The English full-text version of this article is freely available at SpringerLink (under "Supplementary Material").

Publication types

  • Comparative Study
  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / therapeutic use*
  • Chronic Pain / drug therapy*
  • Humans
  • Long-Term Care
  • Neuralgia / drug therapy*
  • Pain Measurement / drug effects
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Analgesics, Opioid