Long-Term Opioid Therapy Tied to Worse Outcomes in Polyneuropathy

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Diabetic Nerve Pain
Most prescriptions for long-term opioid therapy were written by internal or family medicine physicians.

Findings from a retrospective cohort study published in JAMA Neurology show that long-term treatment with opioids is associated with more adverse outcomes in patients with polyneuropathy, including depression, overdose, and opioid dependence.

Polyneuropathy is a common diagnosis in the primary care setting, especially among elderly patients, and has been associated with impairments in functional status. Opioids may be effective for short-term treatment of noncancer pain, but there is less clear evidence for its use in the long term.

E. Matthew Hoffman, DO, PhD, from Mayo Clinic in Rochester, Minnesota, and colleagues sought to better understand the prevalence of long-term opioid use in patients with polyneuropathy, along with any associated effects on functional status, mortality, and adverse outcomes.

The investigators conducted a retrospective population-based cohort study using data obtained from the Rochester Epidemiology Project database. Prescriptions given to patients with polyneuropathy were compared with controls in ambulatory practice from 2006 to 2010, with follow-up conducted through November 2016.

Among the 2892 patients identified with a polyneuropathy diagnosis, 50.6% (n=1464) were treated with opioids for fewer than 90 days, and 18.8% (n=545) were treated with long-term opioid therapy compared with 5.4% (n=780) of the 14,435 control patients who received long-term opioid treatment (odds ratio [OR], 2.4; 95% CI, 2.2-2.8).

Notably, most of the long-term opioid prescriptions were written by internal medicine or family medicine physicians (82.7% combined), with an indication of musculoskeletal pain (52.5%) and polyneuropathy (24.0%).

Patients with a diagnosis of polyneuropathy who received long-term treatment with opioids compared with those who were treated for <90 days were more likely to be female (56.9% vs 46.4%; P <.001) and have comorbidities such as myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, diabetes, renal disease, and chronic pulmonary disease.

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At the end of the study period, patients with polyneuropathy treated with long-term opioids were more likely to continue to report pain (aOR, 2.5), require an assistive device (aOR, 1.9), report difficulty performing activities of daily living or have functional limitations (aOR, 1.7), or report no longer working (aOR, 1.3). Long-term opioid therapy was also associated with opioid overdose (adjusted hazard ratio [aHR], 5.12), opioid dependence (aHR, 2.85), other chemical dependence (aHR, 1.73), and depression (aHR, 1.53).

One limitation of the study the investigators pointed out was the inability to collect data on pain severity, which may have influenced functional status and adverse outcomes in patients on long-term opioid therapy.

With most of the prescriptions for opioid therapy indicated for musculoskeletal pain rather than polyneuropathy, the investigators hypothesized that “it is possible that peripheral and central sensitization occurring in polyneuropathy decreases the pain threshold and patients’ abilities to tolerate nonneuropathic (nociceptive) pain, thus leading to increased rates of long-term opioid prescriptions for nociceptive musculoskeletal pain.”

Overall, the study results demonstrate that long-term opioid therapy in patients with polyneuropathy is associated with worse outcomes. The findings may help guide physicians when counseling patients and influence treatment guidelines and policies.


Hoffman EM, Watson JC, St Sauver J, Staff NP, Klein CJ. Association of long-term opioid therapy with functional status, adverse outcomes, and mortality among patients with polyneuropathy. JAMA Neurol. 2017;74(7):773-779. doi: 10.1001/jamaneurol.2017.0486