Is Topical OTC Capsaicin Effective for Osteoarthritis?

Darrell Hulisz, PharmD


August 10, 2015


Does evidence support the use of topical OTC capsaicin for osteoarthritis pain?

Response from Darrell Hulisz, PharmD
Associate Professor, Department of Family Medicine, Case Western Reserve University, Cleveland, Ohio; Clinical Pharmacist, University Hospitals, Case Medical Center, Cleveland, Ohio

Capsaicin is a naturally occurring alkaloid derived from hot chili peppers that is used topically to treat pain. It comes in a variety of over-the-counter (OTC) formulations (such as creams, gels, liquids, lotions, and transdermal patches) and concentrations, ranging from 0.025% to 0.15%, labeled for temporary treatment of minor pain due to backache, strains, sprains, bruises, cramps, arthritis, or diabetic neuropathy. Qutenza® (capsaicin patch, 8%) is FDA approved for neuropathic pain associated with postherpetic neuralgia and is available by prescription.

The mechanism of action of capsaicin is complex and involves a cascade of events that results in nociceptive fiber dysfunction.[1] Capsaicin affects the transient receptor potential vanilloid 1 (TRPV1) receptor, which is involved in sensing heat, warmth, and pain, as well as substance P, which transmits pain and itch sensations from the peripheral to the central nervous system.[2] When stimulated by capsaicin, the TRPV1 receptor releases sensory neuropeptides and blocks axonal transport of substance P in sensory neurons.[1]Continued application of capsaicin results in further depletion of substance P from peripheral sensory neurons, as well as decreased synthesis and transport of substance P within the neuron.[2] The net effect is a temporary and modest diminution of pain perception that occurs over a period of 2-4 weeks and persists with repeated application.

Capsaicin is used for several types of pain. Randomized controlled studies of topical OTC capsaicin in the treatment of painful diabetic neuropathy have yielded mixed results.[3,4,5]Another systematic review determined moderate to poor efficacy of capsaicin in treating chronic neuropathic or musculoskeletal pain, but noted that it possibly was useful as an adjunctive treatment for patients who are intolerant or unresponsive to conventional therapy.[6]

However, relatively few randomized, prospective clinical trials have specifically investigated topical capsaicin for treating osteoarthritis (OA) pain.[7,8,9,10,11] In a double-blind, randomized study, 70 patients with OA and 31 patients with rheumatoid arthritis applied either capsaicin 0.025% cream or placebo to painful knees for 4 weeks.[7] Most patients continued concurrent arthritis medications. After 4 weeks of capsaicin treatment, rheumatoid arthritis pain was reduced by 57% (P = .003 vs placebo) and OA pain was reduced by 33% (P = .033 vs placebo). After 2 weeks of treatment, 80% of capsaicin recipients experienced some pain reduction. The most common side effect was transient burning at the application site, which resulted in only 2 participants withdrawing from the study.

In a randomized, 28-day study focusing on the treatment of OA pain, capsaicin 0.25% cream applied twice daily (n = 31) was compared with capsaicin 0.025% cream applied 4 times daily (n = 29).[8] Higher-strength capsaicin provided greater pain relief and a more rapid onset of action relative to lower-strength capsaicin. About one half of the patients using 0.25% capsaicin twice daily experienced at least a 50% reduction in pain severity after 2 days of treatment, whereas a 50% reduction in pain severity did not occur until day 14 in the patients using 0.025% capsaicin applied four times daily. The most common adverse effect was transient burning sensation after application. Burning sensations after drug application were greater in the high-potency group at day 2 but declined rapidly in both treatment groups over time. Although 0.25% capsaicin is not commercially available in the United States, this study suggests greater efficacy with higher-strength formulations.

Topical capsaicin 0.075% was studied for relieving hand pain in 21 patients with rheumatoid arthritis (n = 7) and osteoarthritis (n = 14) in a 4-week, double-blind, placebo-controlled, randomized trial.[9] Treatment was applied to each painful hand joint four times daily with an assessment at baseline, and then at 1, 2, and 4 weeks. Compared with placebo, capsaicin reduced tenderness (P < .02) and pain (P < .02) associated with OA but not with rheumatoid arthritis. Localized burning was the only adverse effect reported.

Another study, of 113 patients with OA pain, compared capsaicin 0.025% cream with placebo applied four times daily in a 12-week randomized, multicenter trial.[10] Capsaicin was found to be superior to placebo for pain relief. After 2 weeks of treatment, 81% of patients using capsaicin vs 54% using placebo were improved by physician's global evaluation (P = .03). Similar results were reported by patient's global evaluation. Capsaicin-treated patients reported greater reduction of pain using a visual analog scale. Joint tenderness evaluated by palpation decreased in the capsaicin group at week 4 (P = .03), week 8 (P = .01), and week 12 (P = .01) compared with placebo. About 50% of patients had local burning or stinging at the application site, which resolved by week 12 in most patients.

Further evidence from other clinical trials[11,12] suggests a very modest benefit from OTC capsaicin for OA pain; however, most published evidence is from short-duration studies with small sample sizes. Additionally, the predictable local effect of capsaicin presents difficulty in blinding placebo and active treatment.

The 2012 American College of Rheumatology guidelines for managing osteoarthritis identify topical capsaicin as a conditional treatment for OA of the hand but do not mention OA of the hip or knee.[13] Specific recommendations regarding dosage, formulation, and duration of treatment are not discussed. An advantage of capsaicin is the absence of systemic adverse effects, which offers a treatment alternative for patients with intolerance or contraindications to conventional OA treatment. Potential disadvantages of capsaicin include slow onset of action (2-4 weeks) and multiple daily applications. Topical application of capsaicin also consistently causes localized burning, stinging, or erythema, reportedly worse upon initial application, with attenuation over time. Patients should be cautioned that drug residue should not come in contact with mucous membranes, eyes, or genital areas.


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