The American Academy of Neurology (AAN) has issued updated recommendations for the treatment of painful diabetic polyneuropathy.

According to the new guidelines, several pharmacotherapies have been shown to reduce pain in patients with painful diabetic neuropathy, a condition that can greatly affect quality of life. Four classes of oral medications that have demonstrated efficacy in clinical trials include tricyclic antidepressants (amitriptyline, nortriptyline, imipramine), serotonin-norepinephrine reuptake inhibitors (duloxetine, venlafaxine, desvenlafaxine), gabapentinoids (gabapentin, pregabalin), and sodium channel blockers (carbamazepine, oxcarbazepine, lamotrigine, lacosamide).

“New studies on sodium channel blockers published since the last guideline have resulted in these drugs now being recommended and considered as effective at providing pain relief as the other drug classes recommended in this guideline,” said guideline author Brian C. Callaghan, MD, MS, of the University of Michigan in Ann Arbor and a Fellow of the American Academy of Neurology.

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As all of these treatments were found to be relatively similar with respect to efficacy, other factors such as side effects, patient preferences, comorbidities, and cost should be considered when making treatment decisions.

Following titration to an effective dose, if a treatment fails to reduce pain or if the side effects of the drug outweigh its benefits after approximately 12 weeks, it can be considered a failure, according to the guidelines. When meaningful improvement is not demonstrated with the initial therapy, a trial of a different class of medication may be offered.

It was noted that valproic acid should not be prescribed due to the potential for serious adverse events. In patients of child-bearing potential, the drug should be not be offered at all, while in others, it may be considered but only after other medications have failed.

Additionally, the use of opioids should be avoided. This includes the use of tramadol and tapentadol. “Current evidence suggests that the risks of the use of opioids for painful diabetic neuropathy therapy outweigh the benefits, so they should not be prescribed,” said Callaghan.

For patients who prefer topical therapies, the guidelines state that capsaicin, glyceryl trinitrate spray, and Citrullus colocynthis may be offered. Alternative treatments such as ginko biloba, cognitive behavioral therapy, exercise, Tai Chi, and mindfulness may also be useful, though these interventions were supported by fewer studies.


  1. AAN issues guideline for treatment of painful diabetic neuropathy. News release. December 28, 2021.
  2. Price R, Smith D, Franklin G, et al. Oral and topical treatment of painful diabetic polyneuropathy practice guideline update. Published online December 27, 2021.

This article originally appeared on MPR