AAN guideline on managing painful diabetic polyneuropathy

Reference

Price R, Smith D, Franklin G, et al. Oral and topical treatment of painful diabetic polyneuropathy: practice guideline update summary: report of the AAN Guideline Subcommittee. Neurology 2022;98(1):31-43.

Synopsis

The American Academy of Neurology (AAN) convened a panel to update its 2011 guideline on managing diabetic neuropathy. The panel consisted of the usual suspects but also included patient advocates and methodology experts; persons with financial and intellectual conflicts of interest were explicitly excluded. The panel used modern guideline development methods and prespecified 5 classes of medications to evaluate: gabapentinoids, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), sodium channel blockers (such as carbamazepine, oxcarbazepine, lamotrigine, valproic acid, lacosamide), and SNRI/opioid dual mechanism agents (such as tramadol and tapentadol). Among the gabapentinoids, only gabapentin was more likely than placebo to improve symptoms (standardized mean difference [SMD] 0.50; moderate-quality evidence). Pregabalin (SMD 0.29) and mirogabalin (SMD 0.21) were possibly effective based on low-quality evidence. Among the SNRIs, duloxetine (SMD 0.50) was probably more effective than placebo based on moderate-quality evidence and desvenlafaxine (SMD 0.25) was possibly effective (low-quality evidence). Among the TCAs, only amitriptyline (SMD 0.95) has been adequately studied and the evidence was of low quality. Among the sodium channel blockers, valproic acid (SMD 0.86) has been most widely studied but the studies are of low quality. Other members of this class have single studies of better quality demonstrating moderate effectiveness (overall SMD 0.56). The SNRI/opioid dual mechanism agents, based on 4 moderate-quality studies, are more effective than placebo (SMD 0.62). Although many other oral agents have been evaluated, the panel typically only found single or low-quality studies of each of them and made no recommendations about their use. Among topical medications, capsaicin (SMD 0.30) is possibly more effective than placebo based on low-quality evidence. Based on single studies, it appears that several other topical agents are more effective than placebo: a nitric oxide–releasing patch (Nitrosense; SMD 0.59), Citrullus colocynthis (SMD 0.91), and glyceryl trinitrate spray (SMD 1.19). However, topical clonidine and topical buprenorphine are probably no more effective than placebo. The guideline contains tables describing medication doses and duration of therapy. The panel recommends that clinicians assess patients with diabetic neuropathy for mood and sleep disorders. Finally, the panel noted that it is unlikely for any therapy to eliminate pain — pain patients should be counseled that pain reduction is the goal.