Long-Term Opioids Associated With Worse Functional Status, Adverse Events in Polyneuropathy

Polyneuropathy may increase the likelihood of patients receiving long-term opioid therapy, according to a study recently published in JAMA Neurology.¹ In addition, although chronic pain itself cannot be eliminated as a possible cause of worsened functional status, long-term opioid therapy did not improve functional status in patients and was associated with a higher risk for opioid dependency and overdose.

E. Matthew Hoffman, DO, PhD, from the Department of Neurology at the Mayo Clinic in Rochester, Minnesota, and colleagues conducted a retrospective population-based cohort study of prescriptions given to patients with polyneuropathy (n=2892; 47% women; mean age, 67.5 years) and to control patients (n=14,435, 47% women; mean age, 67.5 years) in ambulatory care between January 2006 and December 2010.

Those with polyneuropathy were prescribed long-term opioids (≥90 days) more often than control patients (18.8% vs 5.4%; P <.001). Opioids most often prescribed to patients with and without neuropathy were oxycodone hydrochloride (45.9% and 41.7%, respectively), hydrocodone bitartrate (16.4% and 20.8%, respectively), and tramadol hydrochloride (14.3% and 16.7%, respectively).

Patients with polyneuropathy who were taking long- vs short-term opioids had multiple functional status markers that worsened even after adjusting for medical comorbidity, including pain (adjusted odds ratio [OR], 2.5; 95% CI, 1.9-3.4), increased reliance on walking aids (adjusted OR, 1.9; 95% CI, 1.4-2.6), and inability to work (adjusted OR, 1.3; 95% CI, 0.8-2.0). Long-term use of opioids did not improve any functional status markers. “[L]ong-term opioid therapy made several markers of functional status worse, including inability to work,” the researchers wrote. “This finding is not dissimilar to the finding that long-term opioid use is associated with disability among those with chronic back pain and other forms of chronic noncancer pain.”^2,3

Adverse events were also more common in those with polyneuropathy who were taking opioids long-term, including depression (adjusted hazard ratio [HR], 1.53; 95% CI, 1.29-1.82), opioid dependence (adjusted HR, 2.85; 95% CI, 1.54-5.47), and opioid overdose (adjusted HR, 5.12; 95% CI, 1.63-19.62).

Summary & Clinical Applicability

“Our results, even when interpreted conservatively, suggest unintended consequences of long-term opioid therapy when it is used for … polyneuropathy. This finding should be considered by physicians counseling patients with neuropathic pain who are considering opioid analgesic therapy, as well as by authors of guidelines, policy, and consensus statements,” the researchers concluded.

The researchers found that pain physicians saw one-fourth of patients with polyneuropathy who were on long-term opioid therapy, but they were only the prescribers of opioids to 3.7% of the patients — findings that are consistent with national trends.⁴

The researchers also noted that neurologists, although often involved with diagnosing and managing polyneuropathy in these patients, were unlikely to be the prescribers of long-term opioids. “Therefore, it is likely that discussing potential benefits, as well as adverse outcomes, of long-term opioid therapy will fall to the primary care clinician,” the researchers wrote.

Study Limitations

• The study is retrospective
• This study used administrative codes to identify polyneuropathy and adverse outcomes of opioids
• This study was based on prescription data without confirmation that the prescriptions were taken as prescribed
• Prescription duration was calculated assuming that patients took their medications as prescribed
• Daily morphine equivalents were not estimated, preventing the researchers form determining a dose effect

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References

1. 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 [published online May 22, 2017]. JAMA Neurol. doi:10.1001/jamaneurol.2017.0486
2. Webster BS, Verma SK, Gatchel RJ. Relationship between early opioid prescribing for acute occupational low back pain and disability duration, medical costs, subsequent surgery and late opioid use. Spine (Phila Pa 1976). 2007;32(19):2127-2132.
3. Eriksen J, Sjogren P, Bruera E, Ekholm O, Rasmussen NK. Critical issues on opioids in chronic non-cancer pain: an epidemiological study. Pain. 2006;125(1-2):172-179.
4. Levy B, Paulozzi L, Mack KA, Jones CM. Trends in opioid analgesic-prescribing rates by specialty, US, 2007-2012. Am J Prev Med. 2015;49(3):409-413.