Clinician Article

The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop.

  • Chou R
  • Turner JA
  • Devine EB
  • Hansen RN
  • Sullivan SD
  • Blazina I, et al.
Ann Intern Med. 2015 Feb 17;162(4):276-86. doi: 10.7326/M14-2559. (Review)
PMID: 25581257
Read abstract Read evidence summary Read full text
  • Rheumatology
    Relevance - 6/7
    Newsworthiness - 6/7
  • Family Medicine (FM)/General Practice (GP)
    Relevance - 6/7
    Newsworthiness - 5/7
  • General Internal Medicine-Primary Care(US)
    Relevance - 6/7
    Newsworthiness - 5/7
  • Internal Medicine
    Relevance - 5/7
    Newsworthiness - 4/7
  • Special Interest - Pain -- Physician
    Relevance - 5/7
    Newsworthiness - 4/7


BACKGROUND: Increases in prescriptions of opioid medications for chronic pain have been accompanied by increases in opioid overdoses, abuse, and other harms and uncertainty about long-term effectiveness.

PURPOSE: To evaluate evidence on the effectiveness and harms of long-term (>3 months) opioid therapy for chronic pain in adults.

DATA SOURCES: MEDLINE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO, and CINAHL (January 2008 through August 2014); relevant studies from a prior review; reference lists; and ClinicalTrials.gov.

STUDY SELECTION: Randomized trials and observational studies that involved adults with chronic pain who were prescribed long-term opioid therapy and that evaluated opioid therapy versus placebo, no opioid, or nonopioid therapy; different opioid dosing strategies; or risk mitigation strategies.

DATA EXTRACTION: Dual extraction and quality assessment.

DATA SYNTHESIS: No study of opioid therapy versus no opioid therapy evaluated long-term (>1 year) outcomes related to pain, function, quality of life, opioid abuse, or addiction. Good- and fair-quality observational studies suggest that opioid therapy for chronic pain is associated with increased risk for overdose, opioid abuse, fractures, myocardial infarction, and markers of sexual dysfunction, although there are few studies for each of these outcomes; for some harms, higher doses are associated with increased risk. Evidence on the effectiveness and harms of different opioid dosing and risk mitigation strategies is limited.

LIMITATIONS: Non-English-language articles were excluded, meta-analysis could not be done, and publication bias could not be assessed. No placebo-controlled trials met inclusion criteria, evidence was lacking for many comparisons and outcomes, and observational studies were limited in their ability to address potential confounding.

CONCLUSION: Evidence is insufficient to determine the effectiveness of long-term opioid therapy for improving chronic pain and function. Evidence supports a dose-dependent risk for serious harms.

PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Clinical Comments

Family Medicine (FM)/General Practice (GP)

For a GP, this is useful information; although, the lack of randomised studies makes conclusions tricky. Harmful effects, especially on the long term seem highly prevalent.

General Internal Medicine-Primary Care(US)

Given the high use of opioids in the US, the timing is good for a critical review of the literature. Although the conclusion is that we lack long term efficacy studies, we hope this might be a wake up call for clinicians.


Rheumatologists tend to avoid the use of opioids, at least in the UK, particularly if they have a pain relief unit nearby (as is frequently the case). However, this is important information for any physician who manages patients with chronic pain.


For rheumatologists but also other doctors who treat patients with non-oncologic pain, this is a very important paper showing that the 'paradigm' that opioids are effective and safe when used during a long period in these patients has definitely ended.

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