Opioid switching to improve pain relief and drug tolerability

Cochrane Database Syst Rev. 2004;(3):CD004847. doi: 10.1002/14651858.CD004847.


Background: Patients with cancer, and increasingly chronic non-cancer pain frequently require strong opioids for pain relief. Morphine is the first-line strong opioid of choice for these patients. While most achieve adequate analgesia with morphine, a significant minority either suffer intolerable side-effects, inadequate pain relief, or both. For these patients switching to an alternative opioid is becoming established clinical practice. However, the evidence for the effectiveness of opioid switching does not appear to be established.

Objectives: The aim of this review was to investigate the usefulness of opioid switching for patients with pain.

Search strategy: Randomised trials that assessed opioid rotation, switching, or substitution in adults or children with acute or chronic pain were sought through electronic databases and by handsearching relevant journals. Date of the most recent search: January 2003.

Selection criteria: The search strategy retrieved no randomised controlled trials, and therefore no studies were available to enable a quantitative synthesis that would assess the effectiveness of the strategy of opioid switching.

Data collection and analysis: Given the lack of RCTs, the review examined all case reports, uncontrolled, and retrospective studies in an attempt to determine the current level of evidence.

Main results: Fifty-two reports were identified, comprising 23 case reports, 15 retrospective studies/audits and 14 prospective uncontrolled studies. The majority of the reports used morphine as first-line opioid and the most frequently used second-line opioid was methadone. All reports, apart from one, concluded that opioid switching is a useful clinical manoeuvre for improving pain control and/or reducing opioid-related side-effects.

Reviewers' conclusions: For patients with inadequate pain relief and intolerable opioid-related toxicity/adverse effects, a switch to an alternative opioid may be the only option for symptomatic relief. However, the evidence to support the practice of opioid switching is largely anecdotal or based on observational and uncontrolled studies. Randomised trials, including 'N of 1' studies, where a patient acts as their own control, are needed: firstly, to establish the true effectiveness of this clinical practice; secondly, to determine which opioid should be used first-line or second-line; and thirdly, to standardise conversion ratios when switching from one opioid to another.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Chronic Disease
  • Humans
  • Morphine / administration & dosage
  • Morphine / adverse effects
  • Neoplasms / complications
  • Pain / drug therapy*


  • Analgesics, Opioid
  • Morphine