Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia oil and clotrimazole - tea tree

Journal of Family Practice, June, 1994 by David S. Buck, David M. Nidorf, John G. Addino

Background. The prevalence of onychomycosis, the most frequent cause of nail disease, ranges from 2% to 13%. Standard treatments include debridement, topical medications, and systemic therapies. This study assesses the efficacy and tolerability of topical application of 1% clotrimazole solution compared with that of 100% Melaleuca alternifolia (tea tree) oil for the treatment of toenail onychomycosis.

Methods. A double-blind, multicenter, randomized controlled trial was performed at two primary care health and residency training centers and one private podiatrist's office. The participants included 117 patients with distal subungual onychomycosis proven by culture. Patients received twice-daily application of either 1% clotrimazole (CL) solution or 100% tea tree (TT) oil for 6 months. Debridement and clinical assessment were performed at 0, 1, 3, and 6 months. Cultures were obtained at 0 and 6 months. Each patient's subjective assessment was also obtained 3 months after the conclusion of therapy.

Results. The baseline characteristics of the treatment groups did not differ significantly. After 6 months of therapy, the two treatment groups were comparable based on culture cure (CL = 11%, TT = 18%) and clinical assessment documenting partial or full resolution (CL = 61%, TT = 60%). Three months later, about one half of each group reported continued improvement or resolution (CL = 55%; TT = 56%).

Conclusions. All current therapies have high recurrence rates. Oral therapy has the added disadvantages of high cost and potentially serious adverse effects. Topical therapy, including the two preparations presented in this paper, provide improvement in nail appearance and symptomatology. The use of a topical preparation in conjunction with debridement is an appropriate initial treatment strategy.

Key words. Onychomycosis; mycoses; nails; nail diseases; clotrimazole; administration, topical.

(J Fam Pract 1994; 38:601-605)

The prevalence of onychomycosis, the most frequent cause of nail disease,(1)(2)(3) ranges from 2% to 13%. Onychomycosis is caused by dermatophyte infections, the most common of which is Trichophyton rubrum; yeast (Candida spp); and occasionally molds. Three treatment modalities are available: debridement to eliminate affected keratin, topical medications, and systemic therapy. Topical therapy may have limited effectiveness because of poor penetration of the medication into the nail.(4)(5)

Oral therapies, beginning with griseofulvin in 1959, have been the "gold standard" treatment for dermatophyte onychomycosis.(6) Unfortunately, cure rates with griseofulvin range from 3% to 38%, and although rates may be higher when combined with toenail avulsion or topical medication or both, no significant follow-up data exist for these combined modalities.(7)(8)(9) Ketoconazole is attractive because it presumably treats yeast as well as dermatophyte onychomycosis and shows a cure rate of 50% to 93% at 1 year,(5)(10)(11) which is much higher than that of griseofulvin. Although side effects are rare, they can include pruritus, idiosyncratic liver dysfunction,(12) and gynecomastia.(10) Furthermore, about 50% of toenail infections recur 4 years after the completion of treatment.(13) Itraconazole has cure rates ranging from 4% to 92% with potentially fewer side effects,(14)(15)(16)(17)(18) but thus far, it has been evaluated only in small studies. Follow-up data beyond 1 year are unavailable. Fluconazole has been used by some physicians for both short- and long-term treatment, but no randomized controlled trials have been performed. Outside the United States, much recent research has focused on oral terbinafine (Lamisil), an active fungicidal agent. Cure rates range from 37% to 82% at 6-month follow-up, with a treatment period as short as 2 weeks(19) to 3 months.(20)(21)(22)(23)(24) Once again, long-term results and side effects are unknown. Only the topical form of terbinafine has been approved in the United States.

In light of the varied cure rates, potential adverse effects, high cost, and significant recurrence rate of oral treatment,(25) effective topical therapy would be desirable as primary therapy or for augmentation of systemic therapies. Although the topical imidazole preparations are commonly used,(1) their efficacy has not been assessed in controlled trials. In a limited study, clotrimazole has been reported to be of mild benefit in the treatment of onychomycosis.(26) Other imidazole preparations used in combination with nail removal have resulted in one report of cure in 13 patients.(5)

Nail tinctures and lacquers are also being tested with promising results.(27) The tincture or lacquer is thought to provide better nail penetration. Several recent studies have examined amorolfine 5% nail lacquer.(28)(29)(30) One large study (N = 456) realized cure rates in the 50% to 74% range.(30)

Tea tree oil comes from a shrublike tree in Australia known as Melaleuca alternifolia. It was named by Captain Cook, who observed the aborigines brewing these leaves for medicinal purposes. In World War I, it was used in first-aid kits for Australian troops to treat burns, bites, and infections. The active ingredient, Terpinen-4-ol, has both antibacterial and antifungal properties.(31)(32) Many brief studies have found this popular home remedy successful in treating a variety of ailments: tinea pedis and onychomycosis,(33)(34) trichomonal vaginitis,(35) and acne(36) (the latter the subject of a randomized controlled trial). Tea tree oil is available over the counter at most health food stores at a cost comparable to that of clotrimazole solution. We report a multicenter, randomized, doubleblind study to compare the efficacy of two topical preparations, tea tree oil and 1% clotrimazole solution, for the treatment of toenail onychomycosis.