A randomized trial of 2 prescription strategies for opioid treatment of chronic nonmalignant pain

J Pain. 2011 Feb;12(2):288-96. doi: 10.1016/j.jpain.2010.09.003. Epub 2010 Nov 26.


The use of opioid medications for treating chronic noncancer pain is growing; however, there is a lack of good evidence regarding their long-term effectiveness, association with substance abuse, and proper prescribing guidelines. The current study directly compares for the first time in a randomized trial the effectiveness of a conservative, hold the line (Stable Dose) prescribing strategy for opioid medications with a more liberal dose escalation (Escalating Dose) approach. This 2-arm, parallel, randomized pragmatic clinical trial followed 135 patients referred to a specialty pain clinic at a Veterans Affairs Hospital for 12 months (94% male and 74% with musculoskeletal pain). Primary outcomes included monthly or quarterly evaluations of pain severity, pain relief from medications, pain-related functional disability, and opioid misuse behaviors. All subjects received identical pain treatment except for the application of treatment group specific strategies for opioid prescriptions. No group differences were found for primary outcomes of usual pain or functional disability although the Escalating Dose group did show a small but significantly larger increase in self-rated pain relief from medications. About 27% of patients were discharged over the course of the study due to opioid misuse/noncompliance, but there were no group differences in rate of opioid misuse.

Perspective: The results of this study demonstrate that even in carefully selected patients there is a significant risk of problematic opioid misuse. Although in general there were no statistically significant differences in the primary outcomes between groups, the escalating dose strategy did lead to small improvements in self-reported acute relief from medications without an increase in opioid misuse, compared to the stable dose strategy.

Publication types

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

MeSH terms

  • Aged
  • Analgesia / methods*
  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / adverse effects
  • Chronic Pain / drug therapy*
  • Codeine / administration & dosage
  • Codeine / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination / methods
  • Female
  • Humans
  • Hydrocodone / administration & dosage
  • Hydrocodone / adverse effects
  • Male
  • Middle Aged
  • Morphine / administration & dosage
  • Morphine / adverse effects
  • Musculoskeletal Diseases / complications
  • Oxycodone / administration & dosage
  • Oxycodone / adverse effects
  • Pain Measurement / methods


  • Analgesics, Opioid
  • Hydrocodone
  • Morphine
  • Oxycodone
  • Codeine