Diabetic peripheral neuropathy pain and pharmacotherapy

Waldfogel et al performed a systematic review of pharmacotherapy for diabetic peripheral neuropathy pain. Similar to four previous systematic reviews, they conclude that serotonin reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and pregabalin are effective medications for this highly prevalent condition. In contrast to previous studies, they conclude that gabapentin is not effective while oxcarbazepine is effective.

For gabapentin, this is an important distinction since it’s in the same class as pregabalin (calcium channel ligands), but much less expensive (~$30 vs. $300 per month). While the standardized mean difference (SMD) for gabapentin was not significantly different than placebo, the magnitude was larger than pregabalins. Furthermore, the class I studies from the AAN guideline showed that the effect size of gabapentin and pregabalin were similar. Moreover, Finnerup et al’s systematic review revealed that the number needed to treat (NNT) for gabapentin is lower than that for pregabalin (7.2 vs. 7.7). Taken together, the difference in evidence for these two drugs is negligible, and also illustrates that a p value <0.05 is an arbitrary cutoff. Similar to TCAs and SNRIs, drugs in the calcium channel ligand class likely have similar effects on neuropathic pain (class effect). For oxcarbazepine, the SMD is significantly different from placebo, but two of the three trials were negative trials and all three were deemed class II studies by the AAN. Further research is needed to clarify whether oxcarbazepine is effective. The authors further state that botulinum toxin is effective therapy for diabetic neuropathic pain. However, the evidence is very weak. Only two trials have been performed, both with fundamental flaws (small and no placebo response). Better trials are needed to determine whether botulin toxin is effective. Finally, the authors found that typical opioids are not effective, but atypical opioids (tramadol, tapentadol) are effective treatments. Given the mounting evidence of increasing morbidity and mortality with opioid treatment, this provides even stronger reason to avoid typical opioids in the treatment of chronic neuropathic pain. Atypical opioids are different from typical opioids in that they have SNRI like effects. This may explain the difference in efficacy, but the question remains whether the benefit outweighs the long term side effects. Overall, this systematic review supports the conclusions of previous studies that SNRIs, TCAs, and calcium channel ligands have the strongest evidence in neuropathic pain whereas opioids should likely be avoided.

Brian C. Callaghan, MD, MS

Brian C. Callaghan, MD, MS

Dr. Brian Callaghan is an Assistant Professor and health services researcher in the Department of Neurology at the University of Michigan Health System. He is fellowship trained in Neuromuscular Disorders. His research focus is on improving the efficiency of neurologic diagnostic testing. He is specifically interested in neuroimaging for headache, which is one of the most common reasons for a patient to seek medical care. His research has shown that headache neuroimaging is common, costly, increasing over time, and often performed in low risk populations. He has also investigated the appropriateness of diagnostic testing in patients with distal symmetric polyneuropathy. His work has demonstrated a high variation in testing for polyneuropathy with most of the costs driven by MRI and electrodiagnostic studies. He completed a Master’s of Science program in Clinical Research Design and Statistical Analysis at the University of Michigan and a healthcare policy fellowship at the Center for Healthcare Research and Transformation (CHRT). He also serves as a member of the Medical Economics and Management (MEM) and Guideline Development, Dissemination, and Implementation (GDDI) committees of the American Academy of Neurology (AAN).

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