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

Educational Objective
To evaluate the prevalence of and outcomes associated with long-term opioid use among patients with polyneuropathy.
1 Credit CME
Key Points

Question  What is the association of long-term opioid therapy with functional status, adverse outcomes, and mortality among patients with polyneuropathy?

Findings  In this population-based cohort study that included data from 1993 patients with polyneuropathy who were receiving opioid therapy, those receiving long-term opioid therapy (≥90 days) were significantly more likely to be diagnosed with depression, opioid dependence, or opioid overdose than those receiving shorter durations of opioid therapy. Self-reported functional status measures were either unimproved or poorer among those receiving long-term opioid therapy.

Meaning  Long-term opioid therapy among patients with polyneuropathy appears to increase the risk of adverse outcomes without benefiting functional status.

Abstract

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.

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Article Information

Accepted for Publication: March 14, 2017.

Corresponding Author: Christopher J. Klein, MD, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (klein.christopher@mayo.edu).

Published Online: May 22, 2017. doi:10.1001/jamaneurol.2017.0486

Author Contributions: Drs Hoffman and Klein had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: All authors.

Acquisition, analysis, or interpretation of data: Hoffman, Watson, Staff, Klein.

Drafting of the manuscript: Hoffman, Klein.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Hoffman.

Obtained funding: Klein.

Supervision: Watson, Staff, Klein.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded by the Mayo Foundation for Medical Education and Research, Mayo Clinic Center for Individualized Medicine, grant RO1 AG034676 from the National Institutes of Health (NIH)–Funded Rochester Epidemiology Project, grant K08 NS065007 from the NIH (Dr Klein), grant K08 CA169443-02 from the NIH (Dr Staff), and grant UL1 RR000135 from the NIH (Clinical and Translational Sciences Award).

Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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