Capsaicin 8% Safe and Effective for Diabetic Peripheral Nerve Pain Therapy

Investigators assessed the efficacy and tolerability of a high-concentration capsaicin 8% patch to treat diabetic peripheral nerve pain, either alone or in combination with standard oral therapies.

A high-concentration capsaicin 8% patch is both effective and well-tolerated as a treatment option for diabetic peripheral nerve pain (DPNP), either alone or in combination with standard oral therapies, according to a review published in the Expert Review of Neurotherapeutics.1

Approximately half of all adults with diabetes experience diabetic peripheral neuropathy; about 25% of these adults experience DPNP that severely affects quality of life and is a significant cause of morbidity.

At this time, there is no approved treatment that can reverse or prevent DPN disease progression. Current pharmacologic management of DPN pain focuses on glycemic control and symptomatic therapies and includes α-2-δ ligands, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors.

Topical treatment modalities for DPNP include low-dose capsaicin creams (0.025%-0.075%). These creams have demonstrated moderate efficacy but are often poorly tolerated because of frequent reapplication needs and burning sensation at the application site.

The US Food and Drug Administration approved the high-concentration capsaicin 8% patch in 2009 for postherpetic neuralgia and in 2020 for DPNP. Before approval, development was intended to achieve prolonged treatment efficacy through a single, high-concentration application.

Investigators undertook multiple clinical studies to address concerns surrounding systemic absorption of capsaicin. Several study protocols identified low absorption rate and a half-life of approximately 1.64 hours.

Researchers have also assessed the therapeutic benefits of capsaicin 8% in multiple patient populations, including in persons with DPNP, HIV-associated neuropathy, postherpetic neuralgia, and chemotherapy-induced peripheral neuropathy. One of these studies — the phase 3, randomized, double-blind, placebo-controlled, multicenter STEP trial — included 186 patients with DPNP who received capsaicin 8% and 183 who did not. 2 Investigators found a statistically significant reduction in the primary study endpoint (percentage change of average daily pain score) from baseline to between weeks 2 through 8 in the treatment group (mean percentage change, −27.4±26.79% vs −20.9±28.92%; P =.025).

Although the STEP study demonstrated both clinical efficacy and tolerability, the PACE study demonstrated longitudinal efficacy, safety, and tolerability over a much longer 52-week follow-up period. 3 This open-label, randomized, controlled, multicenter trial assigned patients to 30- or 60-minute capsaicin 8% applications plus standard of care or standard of care alone. Investigators found similar discontinuation rates across all study groups, and efficacy data demonstrated increased DPNP relief with capsaicin 8% compared with standard of care alone.

“The prolonged pain relief following application of the patch, along with favorable adverse event, tolerability, and systemic side effect profile, make the capsaicin 8% patch a powerful tool to help patients and clinicians treat diabetic nerve pain,” the review authors concluded. “Post-surveillance studies of safety and tolerability of the capsaicin 8% patch in patients with DPNP will likely be forthcoming.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


  1. Abrams RMC, Pedowitz EJ, Simpson DM. A critical review of the capsaicin 8% patch for the treatment of neuropathic pain associated with diabetic peripheral neuropathy of the feet in adults. Expert Rev Neurother. Published online January 11, 2021. doi: 10.1080/14737175.2021.1874920
  2. Simpson DM, Robinson-Papp J, Van J, et al. Capsaicin 8% patch in painful diabetic peripheral neuropathy: a randomized, double-blind, placebo-controlled study. J Pain. 2017;18(1):42-53.
  3. Vinik AI, Perrot S, Vinik EJ, et al. Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study. BMC Neurol. 2016;16(1):251.