Comparing doxepin cream to oral antihistamines for the treatment of itch in burn patients: A multi-center triple-blind randomized controlled trial
Kelly A.A. Kwa,
Anouk Pijpe,
Esther Middelkoop,
Margriet E. van Baar,
Anuschka S. Niemeijer,
Roelf S. Breederveld,
Marianne K. Nieuwenhuis,
H.C. Kuipers,
A. Meij-de Vries,
Z.M. Rashaan,
H. Goei,
N. Trommel,
J. Hiddingh,
D. Allersma,
G.H. van Ramshorst,
W.E. Tuinebreijer
Affiliations
Kelly A.A. Kwa
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands; Department of Traumasurgery, Leiden University Medical Center, K6-R, PO Box 9600, 2300 RC Leiden, the Netherlands; Corresponding author at: Red Cross Hospital, Burn Center, Vondellaan 13, 1942 LE Beverwijk, the Netherlands.
Anouk Pijpe
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands
Esther Middelkoop
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands; Association of Dutch Burn Centers, PO Box 1015, 1940 EA Beverwijk, the Netherlands; Amsterdam UMC, Free University Amsterdam, Department of Plastic, Reconstructive and Hand Surgery, Amsterdam Movement Sciences, PO Box 7057, 1007 MB Amsterdam, the Netherlands
Margriet E. van Baar
Association of Dutch Burn Centers, PO Box 1015, 1940 EA Beverwijk, the Netherlands; Burn Center Maasstad Hospital, PO Box 9100, 3007 AC Rotterdam, the Netherlands; Department of Public Health Erasmus MC, PO Box 2040, 3000 CA Rotterdam, the Netherlands
Anuschka S. Niemeijer
Association of Dutch Burn Centers, PO Box 1015, 1940 EA Beverwijk, the Netherlands; Burn Center, Martini Hospital, PO Box 30033, 9700 RM Groningen, the Netherlands
Roelf S. Breederveld
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands; Department of Traumasurgery, Leiden University Medical Center, K6-R, PO Box 9600, 2300 RC Leiden, the Netherlands
Marianne K. Nieuwenhuis
Association of Dutch Burn Centers, PO Box 1015, 1940 EA Beverwijk, the Netherlands; Burn Center, Martini Hospital, PO Box 30033, 9700 RM Groningen, the Netherlands
H.C. Kuipers
Burn Center, Martini Hospital, PO Box 30033, 9700 RM Groningen, the Netherlands
A. Meij-de Vries
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands
Z.M. Rashaan
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands
H. Goei
Burn Center Maasstad Hospital, PO Box 9100, 3007 AC Rotterdam, the Netherlands
N. Trommel
Burn Center Maasstad Hospital, PO Box 9100, 3007 AC Rotterdam, the Netherlands
J. Hiddingh
Burn Center, Martini Hospital, PO Box 30033, 9700 RM Groningen, the Netherlands
D. Allersma
Department of Clinical Pharmacy and Pharmacology, The University Medical Center, Groningen, PO Box 30.001, 9700 RB Groningen, the Netherlands
G.H. van Ramshorst
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands; Department of Surgery, Free University Amsterdam, PO Box 7057, 1007 MB Amsterdam, the Netherlands
W.E. Tuinebreijer
Burn Center, Red Cross Hospital, PO Box 1074, 1940 EB Beverwijk, the Netherlands; Association of Dutch Burn Centers, PO Box 1015, 1940 EA Beverwijk, the Netherlands
Background: Doxepin cream, an antihistaminic agent, has shown promising results in the treatment of pruritus in burn patients. However, its effectiveness has not been studied comprehensively. Objective: To evaluate whether doxepin cream is more effective than oral antihistamines in reducing pruritus. Methods: We performed a multicenter triple-blind randomized controlled trial of twelve weeks randomizing burn patients ≥18 years with an itch intensity ≥3 on a Visual Analogue Scale (VAS) between doxepin hydrochloride 5% cream with placebo tablet or oral antihistamine (clemastine) with placebo cream. Primary endpoint was change in itch intensity. Secondary endpoints included impact of itch (Burn Itch Questionnaire), quality of life (SF-36), somnolence, and erythema (DermaSpectrometer). Results: Thirty-one (of the intended 108) subjects could be included: 13 were randomized to the doxepin and 18 to the clemastine group. The skewed distribution is attributable to the low inclusion rate. Both groups showed a significant reduction in itch intensity over a period of twelve weeks (doxepin p = 0.043, clemastine p = 0.019) with no difference between both groups in: mean itch intensity difference (p = 0.199), any of the domains (p = 0.940, p = 0.698, p = 0.859) of the Burn Itch Questionnaire, quality of life, somnolence (p = 0.143) and erythema (p = 0.796). Conclusion: The effectiveness of doxepin cream was similar to oral antihistamines in reducing itch. However, considering the study ’s limitations, a superior effect of doxepin cream cannot be completely ruled out. We recommend that future studies use a cross-over design so fewer inclusions are needed to obtain adequate power. Keywords: Itch, Pruritus, Burn, Treatment, Doxepin, Antihistamines
