OTC Transdermal Analgesic Patches in Pain Management

Donna M. Lisi, PharmD, BCPS, BCPP, BCGP, BCACP


US Pharmacist. 2019;44(3):15-21. 

In This Article

Capsaicin or Capsicum Extract

Capsaicin is a resin derived from hot chili peppers of the Capsicum family. Commercially available preparations contain either capsaicin or capsicum oleoresin.[14] It is used topically to treat both nociceptive and neuropathic pain.[5]

Capsaicin is thought to work via several mechanisms of action. Capsaicin interacts with sensory afferents via vanilloid receptors, which are cation channels from the transient receptor potential (TRP) family.[22] There are at least 28 different mammalian TRP membrane channels, which can be activated by heat, cold, pain, tissue osmolarity, oxidative stress, lipids, intracellular calcium concentrations, and topical counterirritants.[22] Vanilloid receptors (TRPV1) are activated by warmth and also by compounds that elicit sensations of heat.[6,23] TRPV3, TRPV4, TRPM (melastatin) 2, TRPM4, and TRPM5 are also activated by heat, whereas TRPA (ankyrin) 1 and TRPM8 detect cool temperatures.[22] Chronic exposure to capsaicin initially stimulates TRPV1 but eventually desensitizes these channels. Capsaicin depletes substance P at nerve afferent endings and temporarily reduces the density of nerve fibers in the skin.[6,23] It also induces cellular degeneration of unmyelinated C fiber afferents; activation of neuronal proteases; interference of axonal transport; and a reduction in the absolute number of C fibers without affecting the number of myelinated fibers.[24]

Due to capsaicin's ability to initiate degeneration of cutaneous autonomic nerve fibers, caution is advised with the use of topical capsaicin in patients at risk of skin ulceration.[25] It can take about 6 weeks for the return of nociception following the discontinuation of capsaicin therapy.[26]

Trials involving capsaicin are difficult to conduct because it is nearly impossible to disguise its unique burning sensation. A systematic review of topical capsaicin for the treatment of chronic pain found that while topical capsaicin was better than placebo for the management of neuropathic and musculoskeletal pain, its efficacy was moderate to poor. Nonetheless, the investigators recommended that topical capsaicin may be useful as an adjunct or as sole therapy for patients who are unresponsive or intolerant to other treatment modalities.[27] Patients in this systematic review were primarily receiving OTC capsaicin cream. No details are provided about the capsaicin patch employed.

An early phase 2, multicenter, randomized, semi–double-blind controlled study comparing the efficacy and safety of 0.625% and 1.25% capsaicin patches to 0.075% capsaicin cream or placebo patches in peripheral neuropathic pain found that only the 0.625%-strength patch and the cream produced a statistically significant improvement in pain after 6 weeks. The 1.25% patch was not effective in relieving pain. Over 90% of patients on the 0.625% patch reported improvement in pain, although this relief was only moderate at best. Minor skin irritation occurred in 47% of patients. The study, although promising, was faulted because of its small sample size (only 60 subjects initially enrolled) and a high dropout rate (23%).[28]

Capsaicin patches 0.1% or 0.25% were not found to be effective in the management of myofascial pain.[29,30]

Beside the stinging, burning, and erythematous reaction that is associated with capsaicin therapy, inhalation of the drug can produce respiratory irritation and cough. Due to its half-life of about 2 hours, the four-times-a-day application of capsaicin cream makes this form of therapy inconvenient; the capsaicin patch helps to ameliorate this problem.[6,28]

"Methyl salicylate—which has both vasodilatory and thermogenic action—should not be given to children (over concern of Reye's syndrome) or those who are allergic to aspirin."