Randomised trial of oral morphine for chronic non-cancer pain

Lancet. 1996 Jan 20;347(8995):143-7. doi: 10.1016/s0140-6736(96)90339-6.


Background: The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction.

Methods: We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine, anti-inflammatory agents, and antidepressants. Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine (active placebo) in doses up to 1 mg twice daily over three-week titration, six-week evaluation, and two-week washout phases. Pain intensity, pain relief, and drug liking were rated weekly and psychological features, functional status, and cognition were assessed at baseline and at the end of each evaluation phase.

Findings: After dose titration in the 46 patients who completed the study, the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On visual analogue scales, the morphine group showed a reduction in pain intensity relative to placebo in period I (p = 0.01) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline (p = 0.02). No other significant differences were detected.

Interpretation: In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / therapeutic use*
  • Benztropine / administration & dosage
  • Benztropine / therapeutic use
  • Chronic Disease
  • Cognition / drug effects
  • Cross-Over Studies
  • Delayed-Action Preparations
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / therapeutic use*
  • Musculoskeletal Diseases / physiopathology
  • Pain / drug therapy*
  • Pain / physiopathology
  • Pain / psychology
  • Pain Measurement
  • Patient Satisfaction
  • Placebos
  • Quality of Life
  • Treatment Outcome


  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Placebos
  • Benztropine
  • Morphine