Prevalence of opioid adverse events in chronic non-malignant pain: systematic review of randomised trials of oral opioids

R Andrew Moore,Henry J Mcquay

doi:10.1186/ar1782

Abstract

Adverse events of opioids may restrict their use in non-cancer pain. Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder. To examine the incidence of common adverse events of opioids in non-cancer pain, a systematic review and meta-analysis of information from randomised trials of all opioids in non-cancer pain was undertaken. Studies used were published randomised trials of oral opioid in non-cancer pain, with placebo or active comparator. Thirty-four trials with 5,546 patients were included with 4,212 patients contributing some information on opioid adverse events. Most opioids used (accounting for 90% of patients) were for treating moderate rather than severe pain. Including trials without a placebo increased the amount of information available by 1.4 times. Because of clinical heterogeneity in condition, opioid, opioid dose, duration, and use of titration, only broad results could be calculated. Use of any oral opioid produced higher rates of adverse events than did placebo. Dry mouth (affecting 25% of patients), nausea (21%), and constipation (15%) were the most common adverse events. A substantial proportion of patients on opioids (22%) withdrew because of adverse events. Because most trials were short, less than four weeks, and because few titrated the dose, these results have limited applicability to longer-term use of opioids in clinical practice. Suggestions for improved studies are made.

Highlights

Opioids are advocated by WHO for cancer pain [1], but their role in chronic non-cancer pain is more controversial
It has been argued that certain types of chronic pain, like neuropathic pain, do not respond to opioids [2], some patients with neuropathic pain have been shown to respond well to opioids, as do patients with chronic nociceptive pain [3]
Most trials and patients were in arthritis or musculoskeletal conditions, with few patients with neuropathic pain, and some in mixed nociceptive and neuropathic conditions (Table 1)

Summary

Introduction

Opioids are advocated by WHO for cancer pain [1], but their role in chronic non-cancer pain is more controversial. At least one recent systematic review has investigated efficacy and safety of oral opioids in placebo-controlled randomised trials in chronic non-malignant pain [11]. It included 11 trials in which patients received different oral opioids, doses, and dosing regimens, over varying periods of time, and in patients with arthritis, musculoskeletal pain, neuropathic pain, and mixed conditions. Adverse event rates could be calculated for several adverse events, and numbers needed to harm were calculated, which were as low as 3 for constipation, and 5 for nausea and somnolence. Constipation (affecting 41%), nausea (32%) and somnolence (29%) were the most common adverse events

Methods

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Discussion

Conclusion