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Effect of topical doxepin cream on skin testing

1995; Elsevier BV; Volume: 96; Issue: 6 Linguagem: Inglês

10.1016/s0091-6749(95)70238-5

1097-6825

Sameh S. Karaz, Jane Moeckli, William Davis, Timothy J. Craig,

Contact Dermatitis and Allergies

Doxepin hydrochloride cream is a new tricyclic antidepressant preparation indicated for topical application in the treatment of atopic dermatitis and lichen simplex chronicus.1Drake LA Fallon JD Sober A Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream.J Am Acad Dermatol. 1994; 31: 613-616Abstract Full Text PDF PubMed Scopus (154) Google Scholar Tricyclic antidepressant compounds are potent antagonists of H 1 and H 2 receptors.2Richelson E Antimuscarinic and other receptor-blocking properties of antidepressants.Mayo Clin Proc. 1983; 58: 40-46PubMed Google Scholar Doxepin is a competitive antagonist of the muscarinic acetylcholine receptor, which accounts for the majority of adverse effects, including blurred vision, dry mouth, and urinary retention.2Richelson E Antimuscarinic and other receptor-blocking properties of antidepressants.Mayo Clin Proc. 1983; 58: 40-46PubMed Google Scholar, 3Gupta MA Gupta AK Ellis CN Antidepressant drugs in dermatology: an update.Arch Dermatol. 1987; 123: 647-652Crossref PubMed Scopus (47) Google Scholar Because of the adverse effect profile of the oral preparation, a topical agent was investigated. It is believed that the antipruritic effect of the cream is secondary to the local antihistaminic effect only. During clinical trials it was suggested that there was minimal percutaneous absorption of topical doxepin.4GenDerm Zonalon cream (doxepin hydrochloride cream), 5%. A clinical review. GenDerm Corporation, Lincoln, Illinois1994Google Scholar Plasma levels of topical doxepin ranged from 0 to 47 ng/ml, whereas plasma levels of orally administered doxepin have been reported to range from 30 to 150 ng/ml.4GenDerm Zonalon cream (doxepin hydrochloride cream), 5%. A clinical review. GenDerm Corporation, Lincoln, Illinois1994Google Scholar Patients with atopic dermatitis often require skin testing to assess for specific allergies. Before immediate hypersensitivity skin testing is performed, it is important to discontinue all antihistamines because they will suppress skin test responses. It is also important to determine whether and how long a medication will suppress skin test responses to avoid false-negative results. The intent of this study was to demonstrate whether and how long histamine skin test responses were suppressed after topical use of doxepin and to determine whether systemic absorption could account for the suppression. Five healthy faculty members and fellows with normal skin were recruited from the Allergy Department of the University of Iowa for the study. They had not taken antihistamines or oral steroids for 2 weeks or astemizole for at least 3 months. No other topical products were used, and none of these medications were allowed for the duration of the study. One inch of the cream was gently massaged on an area of approximately 6 × 12 cm on the volar surface of the right forearm four times a day for 4 to 6 days. Four individuals underwent epicutaneous skin testing, and one underwent intradermal skin testing. Histamine (histamine phosphate, 2.75 mg/ml) and a negative control solution were applied on both arms (volar surface) on day 0 and at least every 3 days thereafter. Skin test reagents from Center Labs Inc. (Port Washington, N.Y.) were used. The skin test device used was the Prick Lancetter (Hollister-Stier, Spokane, Wash.). The erythema and wheal were measured in two directions and recorded in millimeters. The degree of itching caused by the skin test was documented in a daily log with a scale of 1 to 6. Skin testing was repeated until positive results were obtained. Skin test response was considered suppressed if the histamine wheal was less than 3 mm for the epicutaneous and less than 5 mm for the intradermal. Results of skin tests with histamine became negative after 1 to 3 days of therapy (Table I). Skin test response was suppressed at the site of application and on the untreated volar surface. This suppression persisted for up to 11 days after the medication was discontinued. The pruritus associated with skin testing was completely suppressed, even at the sites where doxepin was not applied. The decrease in pruritus continued as long as the histamine skin test responses were suppressed. TABLE IPatients treated with topical doxepin Patient 1 Patient 2* Patient 3 Patient 4 Patient 5RightLeftRightLeftRightLeftRightLeftRightLeftDuration of therapy(days)6None4None4None5None5NoneDay skin test results became negative3333332211Duration of skin test suppression (days)8810106676911Wheal size (mm) Day 06 × 54 × 58 × 89 × 94 × 45 × 55 × 55 × 54 × 45 × 5 Day 50 × 00 × 03 × 34 × 40 × 00 × 00 × 00 × 00 × 00 × 0 Day 124 × 45 × 59 × 98 × 84 × 44 × 43 × 35 × 51 × 12 × 2Results of epicutaneous skin testing with histamine are displayed. Medication was applied only on the right volar area. Skin testing was done on the volar area of right and left arms. Duration of therapy and skin test suppression are given in days.*Tested intradermally. Open table in a new tab Results of epicutaneous skin testing with histamine are displayed. Medication was applied only on the right volar area. Skin testing was done on the volar area of right and left arms. Duration of therapy and skin test suppression are given in days. *Tested intradermally. Topical doxepin is effective in the inhibition of histamine-induced wheal-and-flare reactions, and its effect seems to be secondary to both local and systemic absorption. This absorption was associated with the suppression of histamine skin test response after 1 to 3 days of therapy. The suppression was noticed in both the doxepin-treated and untreated areas, implying considerable systemic absorption. Our observation of systemic absorption is further supported by previous reports of drowsiness associated with doxepin use.4GenDerm Zonalon cream (doxepin hydrochloride cream), 5%. A clinical review. GenDerm Corporation, Lincoln, Illinois1994Google Scholar Inhibition of histamine-induced pruritus by several topical tricyclic antidepressants, including doxepin, was demonstrated in earlier studies.5Bernstein JE Whitney DH Soltani K Inhibition of histamine-induced pruritus by topical tricyclic antidepressants.J Am Acad Dermatol. 1981; 5: 582-585Abstract Full Text PDF PubMed Scopus (74) Google Scholar In our study the pruritus associated with histamine skin testing was also suppressed and did not return until the skin test result became positive, 6 to 11 days after therapy was stopped. The inhibition of skin test response, systemically by focal percutaneous absorption, suggests that the antihistaminic effect of topical doxepin does not differ from the effect of orally administered antihistamines. Despite this, topical doxepin is well tolerated with few adverse effects other than sedation.1Drake LA Fallon JD Sober A Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream.J Am Acad Dermatol. 1994; 31: 613-616Abstract Full Text PDF PubMed Scopus (154) Google Scholar As reported by others, the adverse effect profile of the topical preparation seems to be minimal when compared with orally administered doxepin.1Drake LA Fallon JD Sober A Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream.J Am Acad Dermatol. 1994; 31: 613-616Abstract Full Text PDF PubMed Scopus (154) Google Scholar, 3Gupta MA Gupta AK Ellis CN Antidepressant drugs in dermatology: an update.Arch Dermatol. 1987; 123: 647-652Crossref PubMed Scopus (47) Google Scholar In summary, it is questionable whether topical doxepin has any benefit over the traditional treatment regimen for atopic dermatitis. Topical lubricants and topical corticosteroids, together with oral antihistamines, are effective and inexpensive. Topical doxepin absorption is significant and will suppress histamine skin test responses. It is unknown how much suppression of allergen skin test response will occur. Therefore the medication should be stopped approximately 2 weeks before immediate hypersensitivity skin testing is done.