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Watchful Dosing of Morphine or Morphine Equivalent Dosing in the Treatment of Chronic Non-Cancer Pain: A Review of the Clinical Evidence

Last updated: June 8, 2012
Project Number: RC0353-000
Product Line: Rapid Response
Report Type: Summary with Critical Appraisal
Result type: Report

Report in Brief

Context
Chronic non-cancer pain affects 15% to 30% of Canadians. It persists for longer than three months and is frequently related to back pain, osteoarthritis, fibromyalgia, and headaches. Opioids are commonly used to manage pain, but for many patients analgesic efficacy is not maintained over long time periods. Patients require higher doses to maintain the same level of pain relief. Higher doses come with increased risks of adverse events and side effects including overdose, fractures from falls, hormonal changes, and increased pain sensitivity.

Technology
Opioid pain medications available in Canada include codeine (e.g., Tylenol No. 3), tramadol, buprenorphine, morphine, hydromorphone (e.g., Dilaudid), oxycodone (e.g., OxyContin, OxyNEO, or Percocet), fentanyl, and methadone. Morphine equivalents (MEQ) provide a common terminology to discuss opioid dosing. For example, 13 mg of oxycodone is equivalent to 20 mg of MEQ. Or, 133 mg of codeine is also 20 mg of MEQ. Opioid analgesic conversion tables can be found at http://nationalpaincentre.mcmaster.ca.

Issue
The 2010 Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain advises that chronic pain can be managed in most patients with dosages at or below 200 mg per day of morphine or its equivalent. Clinicians are advised to reassess the response to therapy and risks of harm before exceeding thiswatchful dose. What is less clear for policy-makers, however, is whether there are important public health safety concerns at morphine- equivalent doses below 200 mg per day.

Methods
A limited literature search of key resources was conducted, and titles and abstracts of the retrieved publications were reviewed. Full-text publications were evaluated for final article selection according to predetermined selection criteria (population, intervention, comparator, outcomes, and study designs).

Key Messages
Risk of opioid-related death increased as prescribed doses increased.

Risk of opioid-related death increased with prescriptions above 20 mg/day:

  • 50 mg to 99 mg/day = 2 × risk
  • 100 mg to 199 mg/day = 2 × risk
  • More than 200 mg/day = 3 × risk.

Patients receiving doses of more than 100 mg/day had 7× risk of death compared with those receiving less than 20 mg/day.

The link between opioid dose and frequency of emergency department visits is unclear.

Based on limited evidence.

Results
The literature search produced 640 citations, with 13 additional studies identified from the grey literature. Of these, 50 articles were deemed potentially relevant, with 6 meeting the criteria for inclusion in this review: 4 non-randomized studies and 2 evidence-based guidelines.

Question

  1. What is the clinical evidence regarding the safety of different watchful doses of morphine (or equivalent) for the treatment of chronic non-cancer pain?
  2. What are the evidence-based guidelines regarding a watchful dose of morphine (or equivalent) for the treatment of chronic non-cancer pain?

Key Message

The evidence base around a watchful dose threshold for morphine or equivalent opioid dosing was limited in both quality and quantity. The evidence to support a watchful dose of morphine or morphine equivalent opioid dosing of greater than 200 mg/day in chronic non-cancer pain (CNCP) is limited in both quality and quantity; however, there is also little evidence to support a lower threshold dose.The paucity of evidence for watchful dosing is likely reflective of larger gaps in evidence in the topic of CNCP management in general, including around the appropriate use of opioids.