The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis
The addition of topical doxepin to corticosteroid therapy: an improved treatment regimen for atopic dermatitis
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DOI：
10.1046/j.1365-4362.1999.00505.x
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发表时间：
1999-02-01
影响因子：
3.6
通讯作者：
Bernstein, JE
中科院分区：
文献类型：
--
作者：
Berberian, BJ;Breneman, DL;Bernstein, JE
349例提供书面知情同意书的过敏性特应性皮炎患者参加了本研究。入组患者必须在入组前至少1周内每天发生中度至重度皮炎伴湿疹性病变，有特应性家族史和/或特应性皮炎个人史，受特应性皮炎影响的体表面积≤ 25%，一般健康状况良好。入组后，要求患者在入组研究前至少4周停用全身性皮质类固醇，并在入组前至少1周停用抗炎药和中枢神经系统活性药物。此外，入组前至少2天内，不允许在治疗部位使用外用药物。有治疗部位感染、其他并发皮肤病或妊娠或哺乳期的患者被排除在研究之外，这是一项为期8天的多中心、双盲、平行设计研究，评估在局部皮质类固醇治疗中加入局部多塞平与局部皮质类固醇治疗本身的疗效。将所有试验产品掺入与盐酸多塞平乳膏相同的乳膏基质中。使用计算机生成的随机化时间表，将患者分配到接受乳膏的治疗组，所述乳膏包含：（1）2.5%氢化可的松;（2）0.1%曲安奈德;（3）2.5%氢化可的松和5%盐酸多塞平;（4）0.1%严重度的丙酮和5%盐酸多塞平。指导患者每天使用研究乳膏4次，治疗8天。医生最初将患者的皮炎评定为轻度、中度或重度，将其特应性皮炎评定为轻度、中度、显著或重度。由患者完成针对尿道炎严重程度的基线视觉模拟量表（VAS），包括在相对两端标记为“无瘙痒”和“可想象的最严重瘙痒”的100 mm水平线，以量化在研究入组前一周和研究期间每天经历的尿道炎强度。此外，在研究期间，每例患者每天通过在相对两端标记100 mm垂直线（标记为“瘙痒未缓解”和“瘙痒完全缓解”）完成尿道炎缓解的VAS。基线评价后，安排在第2、3、4和8天进行后续访视。在每次就诊时，医生检查患者的日常VAS，以记录皮炎缓解的总体评价，并在五点量表上对皮炎的总体变化进行评分，从更差到更好。所有不良反应的报告也被记录下来，协方差分析被用来评估疼痛的严重程度。使用行平均评分和ridit分配评分，在医生总体评价（皮炎和皮炎）分析中对有序应答类别进行Cochran-Mantel-Haenszel（CMH）分析。所有疗效变量均采用意向治疗分析。统计学显著性定义为p < 0.05（双尾）。
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).