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Prescriptions for opioids as a first-line treatment for painful diabetic peripheral neuropathy (DPN) outnumbered those for other medications between 2014 and 2018, despite the fact that the former is not recommended, new research indicates.

“We know that for any kind of chronic pain, opioids are not ideal. They’re not very effective for chronic pain in general and they’re definitely not safe,” senior author Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic in Rochester, Minnesota, cheap avodart told Medscape Medical News.

That’s true even for severe DPN pain or painful exacerbations, she added.

“There’s a myth that opioids are the strongest pain meds possible…For painful neuropathic pain, duloxetine [Cymbalta], pregabalin [Lyrica], and gabapentin [Neurontin] are the most effective pain medications based on multiple studies and extensive experience using them,” she explained.

“But I think the public perception is that opioids are the strongest. When a patient comes with severe pain, I think there’s that kind of gut feeling that if the pain is severe, I need to give opioids.”

What’s more, she noted, “Evidence is emerging for other harms, not only the potential for dependency and potential overdose, but also the potential for opioid-induced hyperalgesia. Opioids themselves can cause chronic pain. When we think about using opioids for chronic pain, we are really shooting ourselves in the foot. We’re going to harm patients.”

The American Diabetes Association DPN guidelines essentially say as much, advising opioids only as a tertiary option for refractory pain, she observed.

The new findings, from a retrospective review of Mayo Clinic electronic health data, were published online in JAMA Network Open by Jungwei Fan, PhD, also of Mayo Clinic, and colleagues.

Are Fewer Patients With DPN Receiving Any Treatment Now?

The data also reveal that while opioid prescribing dropped over the study period, there wasn’t a comparable rise in prescriptions of recommended pain medications, suggesting that recent efforts to minimize opioid prescribing may have resulted in less overall treatment of significant pain. (The study had to be stopped in 2018 when Mayo switched to a new electronic health record system, McCoy explained.)

“The proportion of opioids among new prescriptions has been decreasing. I’m hopeful that the rates are even lower now than they were 2 years ago. What was concerning to me was the proportion of people receiving treatment overall had gone down,” McCoy noted.

“So, while it’s great that opioids aren’t being used, it’s doubtful that people with DPN are any less symptomatic. So I worry that there’s a proportion of patients who have pain who aren’t getting the treatment they need just because we don’t want to give them opioids. There are other options,” McCoy said, including nonpharmacologic approaches.

Opioids Dominated in New-Onset DPN Prescribing During 2014-2018

The study involved 3495 adults with newly-diagnosed DPN from all three Mayo Clinic locations in Rochester, Minnesota; Phoenix, Arizona; and Jacksonville, Florida during the period 2014-2018. Of those, 40.2% (1406) were prescribed a new pain medication after diagnosis. However, that proportion dropped from 45.6% in 2014 to 35.2% in 2018.

The odds of initiating any treatment were significantly greater among patients with depression (odds ratio [OR], 1.61), arthritis (OR, 1.21), and back pain (OR, 1.34), but decreased over time among all patients.   

Among those receiving drug treatment, opioids were prescribed to 43.8%, whereas guideline-recommended medications (gabapentin, pregabalin, and serotonin-norepinephrine reuptake inhibitors including duloxetine) were prescribed to 42.9%.

Another 20.6% received medications deemed “acceptable” for treating neuropathic pain, including topical analgesics, tricyclic antidepressants, and other anticonvulsants.

Males were significantly more likely than females to receive opioids (OR, 1.26), while individuals diagnosed with comorbid fibromyalgia were less likely (OR, 0.67). Those with comorbid arthritis were less likely to receive recommended DPN medications (OR, 0.76).

Use of opioids was 29% less likely in 2018 compared with 2014, although this difference did not achieve significance. Similarly, use of recommended medications was 25% more likely in 2018 compared with 2014, also not a significant difference.

McCoy Offers Clinical Pearls for Treating Pain in DPN

Clinically, McCoy said that she individualizes treatment for painful DPN.

“I tend to use duloxetine if the patient also has a mood disorder including depression or anxiety, because it can also help with that. Gabapentin can also be helpful for radiculopathy or for chronic low back pain. It can even help with degenerative joint disease like arthritis of the knees. So, you maximize benefit if you use one drug to treat multiple things.”

All three recommended medications are generic now, although pregabalin still tends to be more expensive, she noted. Gabapentin can cause drowsiness, which makes it ideal for a patient with insomnia but much less so for a long-haul truck driver. Duloxetine doesn’t cause sleepiness. Pregabalin can, but less so than gabapentin.  

“I think that’s why it’s so important to talk to your patient and ask how the neuropathy is affecting them. What other comorbidities do they have? What is their life like? I think you have to figure out what drug works for each individual person.”

Importantly, she advised, if one of the three doesn’t work, stop it and try another. “It doesn’t mean that none of these meds work. All three should be tried to see if they give relief.”

Nonpharmacologic measures such as cognitive behavioral therapy, acupuncture, or physical therapy may help some patients as well.

Supplements such as vitamin B12 — which can also help with metformin-induced B12 deficiency — or alpha-lipoic acid may also be worth a try as long as the patient is made aware of potential risks, she noted.

McCoy hopes to repeat this study using national data. “I don’t think this is isolated to Mayo…I think it affects all practices,” she said.

Since the study, “We [Mayo Clinic] have implemented practice changes to limit use of opioids for chronic pain…so I hope it’s getting better. It’s important to be aware of our patterns in prescribing.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases. McCoy reported receiving grants from the AARP Quality Measure Innovation program through a collaboration with OptumLabs and the Mayo Clinic’s Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery.

JAMA Netw Open. Published online January 28, 2021. Full text

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