Safety concerns with long-term opioid use

Expert Opin Drug Saf. 2016 Jul;15(7):955-62. doi: 10.1080/14740338.2016.1177509. Epub 2016 Apr 26.


Introduction: The benefits of opioid therapy must be balanced by any adverse effects. In recent years, prescription opioids have been increasingly prescribed, but have also been associated with increased abuse, overdose and death.

Areas covered: This review will categorize the common risks of opioid administration. Recognized adverse effects of opioid therapy include constipation, tolerance, endocrinopathies, sleep disorders, cognitive effects, respiratory depression, overdose and addiction. Studies have shown that there is increased risk of overdose and death with higher daily opioid doses, particularly above a morphine equivalent oral daily dose of 100 milligrams. Extended-release/long acting (ER/LA) opioid formulations may be beneficial for the compliant patient, yet may expose a higher risk for abuse if used inappropriately since each tablet carries a larger dose of medication.

Expert opinion: Prospective, controlled one-year trials are needed to establish the efficacy and safety profile of chronic opioid therapy. In addition to the well known side effects of chronic opioid therapy, the influence and serious effect of opioids on sleep and central sleep apnea is only recently being investigated. The lowest possible daily opioid must be used to manage chronic pain, and all clinicians should be cautious in the use of daily morphine equivalent doses above 50-100 milligrams.

Keywords: Chronic pain; abuse deterrence; extended-release; naloxone; naltrexone; opioids.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Chronic Pain / drug therapy*
  • Delayed-Action Preparations
  • Dose-Response Relationship, Drug
  • Drug Overdose
  • Drug Tolerance
  • Humans
  • Opioid-Related Disorders / complications
  • Opioid-Related Disorders / epidemiology*
  • Time Factors


  • Analgesics, Opioid
  • Delayed-Action Preparations