The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis

Three hundred and forty-nine (349) patients with pruritic atopic dermatitis who provided written informed consent participated in this study. To enter, patients had to have experienced moderate to severe pruritis accompanying their eczematous lesions daily for at least 1 week prior to enrollment, a family history of atopy and/or a personal history of atopic dermatitis, 25% or less body surface area affected by atopic dermatitis, and good general health. After enrollment, patients were required to discontinue systemic corticosteroids at least 4 weeks prior to study entry as well as antipruritic and central nervous system-active medications at least 1 week before entry. In addition, no topical medications were permitted to be applied to treatment sites for at least 2 days before entry. Patients who had infected treatment sites, other concurrent cutaneous conditions, or who were pregnant or lactating were excluded from the study. This was an 8-day multicenter double-blind parallel-design study assessing eh effects of adding topical doxepin to topical corticosteroid treatment vs. the topical corticosteroid treatment itself. All test products were incorporated in an identical cream base to that for doxepin hydrochloride cream. Using a computer-generated randomization schedule, patients were assigned to treatment groups receiving creams containing: (1) 2.5% hydrocortisone; (2) 0.1% triamcinolone acetonide; (3) 2.5% hydrocortisone and 5% doxepin hydrochloride; (4) 0.1% severity acetonide and 5% doxepin hydrochloride. Patients were instructed to apply the study cream four times daily for 8 days of treatment. The physician initially rated the patients' pruritis as mild, moderate, or severe, and their atopic dermatitis as mild, moderate, marked, or severe. A baseline visual analog scale (VAS) for pruritis severity, consisting of a 100-mm horizontal line labeled "no itch" and "worst itch imaginable" at opposite ends, was completed by the patients to quantify the intensity of pruritis experienced during the week before study entry and daily during the study. Additionally, daily during the study, each patient completed a VAS for pruritis relief by marking a 100-mm vertical line labeled "no relief from itching" and "complete relief from itching" at opposite ends. After the baseline evaluation, subsequent visits were scheduled for days 2, 3, 4, and 8. At each visit, the physician reviewed the patient's daily VASs to record a global evaluation of pruritis relief and rated the overall change in dermatitis on a five-point scale ranging from much worse to much better. Any reports of adverse effects were also recorded. Analysis of covariance was used to assess the VAS for pruritis severity. With the use of the row mean score with ridit assigned scores, Cochran-Mantel-Haenszel (CMH) analysis for ordered response categories was performed in the analysis of the physicians' global evaluations (pruritis and dermatitis). Intent-to-treat analysis was used for all efficacy variables. Statistical significance was defined as p < 0.05 (two-tailed).