Association of Long-term Opioid Therapy With Functional Status, Adverse Outcomes, and Mortality Among Patients With Polyneuropathy

JAMA Neurol. 2017 Jul 1;74(7):773-779. doi: 10.1001/jamaneurol.2017.0486.


Importance: Polyneuropathy is one of the most common painful conditions managed within general and specialty clinics. Neuropathic pain frequently leads to decisions about using long-term opioid therapy. Understanding the association of long-term opioid use with functional status, adverse outcomes, and mortality among patients with polyneuropathy could influence disease-specific decisions about opioid treatment.

Objectives: To quantify the prevalence of long-term opioid use among patients with polyneuropathy and to assess the association of long-term opioid use with functional status, adverse outcomes, and mortality.

Design, setting, and participants: A retrospective population-based cohort study was conducted of prescriptions given to patients with polyneuropathy and to controls in ambulatory practice between January 1, 2006, and December 31, 2010, to determine exposure to long-term opioid use as well as other outcomes. The latest follow-up was conducted through November 25, 2016.

Exposures: Long-term opioid therapy, defined by 1 or multiple consecutive opioid prescriptions resulting in 90 continuous days or more of opioid use.

Main outcomes and measures: Prevalence of long-term opioid therapy among patients with polyneuropathy and controls. Patient-reported functional status, documented adverse outcomes, and mortality were compared between patients with polyneuropathy receiving long-term opioid therapy (≥90 days) and patients with polyneuropathy receiving shorter durations of opioid therapy.

Results: Among the 2892 patients with polyneuropathy (1364 women and 1528 men; mean [SD] age, 67.5 [16.6] years) and the 14 435 controls (6827 women and 7608 men; mean [SD] age, 67.5 [16.5] years), patients with polyneuropathy received long-term opioids more often than did controls (545 [18.8%] vs 780 [5.4%]). Patients with polyneuropathy who were receiving long-term opioids had multiple functional status markers that were modestly poorer even after adjusting for medical comorbidity, including increased reliance on gait aids (adjusted odds ratio, 1.9; 95% CI, 1.4-2.6); no functional status markers were improved by long-term use of opioids. Adverse outcomes were more common among patients with polyneuropathy receiving long-term opioids, including depression (adjusted hazard ratio, 1.53; 95% CI, 1.29-1.82), opioid dependence (adjusted hazard ratio, 2.85; 95% CI, 1.54-5.47), and opioid overdose (adjusted hazard ratio, 5.12; 95% CI, 1.63-19.62).

Conclusions and relevance: Polyneuropathy increased the likelihood of long-term opioid therapy. Chronic pain itself cannot be ruled out as a source of worsened functional status among patients receiving long-term opioid therapy. However, long-term opioid therapy did not improve functional status but rather was associated with a higher risk of subsequent opioid dependency and overdose.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects*
  • Comorbidity
  • Depression / epidemiology*
  • Drug Prescriptions / statistics & numerical data*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Minnesota / epidemiology
  • Opioid-Related Disorders / epidemiology*
  • Opioid-Related Disorders / etiology
  • Polyneuropathies / drug therapy*
  • Polyneuropathies / epidemiology*
  • Prescription Drug Overuse / statistics & numerical data*
  • Retrospective Studies
  • Time Factors


  • Analgesics, Opioid