Topical Doxepin Cream is Effective in Relieving Severe Pruritis Caused by Burn Injury: A Preliminary Study

Robert H. Demling, MD; Leslie DeSanti, RN


Wounds. 2001;13(6) 

In This Article

Abstract and Introduction

We studied the effect of a potent topical histamine H1 and H2 receptor blocker, doxepin, on severe burn wound pruritus. We compared the response of doxepin cream in 20 patients with healed itching burn wounds, using the standard of care, which included oral antihistamines, skin moisturizers, and sedatives. The patients (all outpatients) were first assessed as to the degree of itching using the 0 to 10 pain scale with an initial assessment and a take-home chart for a seven-day period after which all patients were placed on the topical doxepin alone, and a daily pruritus assessment was made for seven days. At the end of the doxepin-treatment period, wounds were assessed, after which the previous standard of care was resumed. The degree of pruritus decreased significantly with the use of doxepin cream, decreasing from a value of 7 ± 2 on standard care to a value of 3 ± 1 with the doxepin cream. The response was noted within 15 minutes, and no tachyphylaxis was noted. We also noted a significant decrease in wound erythema. Some somnolence was noted in 20 percent of patients, which decreased with two to three days of doxepin use. The degree of itching and degree of wound erythema returned to pre-doxepin levels with a return to standard care therapy. We concluded that a topical doxepin cream is effective in decreasing wound pruritus in burn patients with results superior to oral antihistamines, skin moisturizers, and sedatives.

Severe pruritus or itching is a common and disabling problem in patients after burn injury.[1,2,3,4,5] The mechanism is not clearly defined, but increased histamine release from the healed wound appears to play a role. Current standard of care is the use of antihistamines. Wound erythema is also typically found.[5,6] The increased mast cell population in the burn wound is likely the source.[1,2,3,4,5] It is known that histamine release occurs from a healed wound with minimal wound manipulation and is further exacerbated by increased skin temperature.[5,6,7,8]

Histamine then appears to trigger local wound surface pain fibers, likely C fibers, through activation of H1 receptors. Since itch is considered a form of pain, the same fibers are felt to produce both itch and burn wound pain.[5,6,7,8,9] In addition, there are a number of studies indicating that histamine release in burn scar will actually increase the degree of erythema and scar, which appears to further increase itching.[10,11]

The pruritus is often refractory to standard management, which includes oral antihistamines, skin moisturizers, and often the addition of opioids, sedatives, and pressure garments, the latter felt to decrease histamine release.[1,2,3] Less than 20 percent of burn patients with severe itch obtain satisfactory control with these approaches, resulting in a significant level of discomfort and decreased quality of life. There is no current effective treatment for this problem.[1,2,3,4,5] Topical corticosteroids are not used on newly healed burns due to the risk of thinning of the skin and risk of infection.

Doxepin, a tricyclic compound, has been found to have potent histamine receptor blocking properties.[12,13,14] Doxepin, currently available in a five-percent topical cream, has been found to be approximately 50 times more potent than hydroxyzine and nearly 800 times more potent than diphenhydramine as an antihistamine. Doxepin cream has been found to control the pruritus of atopic dermatitis, eczema, and urticaria -- all histamine induced -- with results superior to the use of steroid cream or oral antihistamines.[10,11,12,15] Serum levels using the cream are usually immeasurable but when detected, are over 25 times lower than the serum level required for the doxepin to have any therapeutic central nervous system activity.[16,17]

Our objective was to test the efficacy of doxepin cream* in patients with burn wound pruritis not controlled adequately by standard treatment modalities.