Standard Treatment Or topical doxepin against Pruritus in burn patients

Pruritus is a common problem in 40-87% of patients with healed burn wounds.
Chronically pruritic wounds affect quality of life and can inhibit healing due
to recurrent scratching. Histamine is believed to be an important chemical
mediator in the pathogenesis of pruritus associated with skin disorders.
Histamine release also causes increased surface blood flow, which can lead tot
a red skin surface. Standard treatment of pruritus involves oral administration
of antihistamins, moisturizer and pressure garments, but this treatment fails
in a great part of chronically itching burn patients. Little evidence is
available on the treatment of post-burn pruritus, and a review has stressed the
need for prospective, randomized controlled trials.
As regards to the agents with a peripheral action on the pruritic pathway,
Doxepin shows great potential in burns literature because of the effectiveness
and few adverse effects. Two studies have been published on the use of doxepin
hydrochloride 5% cream in burn patients by Demling and DeSanti [Demling 2002
and Demling 2003]. These studies showed a significantly superior effect of
doxepin hydrochloride 5% cream against pruritus compared to standard treatment
in burn patients. Proof of efficacy is limited as high quality randomized
trials have not been performed.

To evaluate whether doxepin hydrochloride 5% cream is more effective in
reducing pruritus in burn patients than standard treatment (clemastine).

The study will be a multi-centre double-blind randomized -controlled trial.

Patients will be randomized between:
1) Doxepin cream + placebo tablet or
2) Neutral cream + oral selective antihistamine (clemastine)

Patients are allowed to use pressure garnments and escape moisturizer if
needed.

Patients will visit the out-patient clinic at randomization (0 weeks), 2 weeks,
6 weeks and 12 weeks. During these visits assesment of erythema will take
place. Assesments are scheduled during regular follow-up and are non invasive.
Quality of life and quality of itch questionnaires will be filled in at
baseline and at 12 weeks. Completing these questionnaire will take
approximately fifteen minutes. VAS scores for pruritus, experienced somnolence,
used studymedication, hydrating cream and pressure garnments will be recorded
daily during the first 2 weeks, at 6 weeks and at 12 weeks. This takes a few
minutes each time.

Patients with burns who enter the study have a potential benefit of a marked
reduction in pruritus by receiving doxepin cream 5% instead of standard
treatment. They may however, suffer from some stinging and somnolence during
the first couple of days. The effect of alcohol can be potentiated. Reported
risks for doxepin hydrochloride 5% cream include development of allergic
contact dermatitis and toxicity in case of topical overdose. Systemic effects
which have been observed with orally administered doxepin hydrochloride are
rarely observed with topical Xepin. These may include anticholinergic effects
(dry mouth, changes in taste, dry eyes, blurred vision, urinary retention);
central nervous system effects other than drowsiness (headaches, fever,
dizziness); and gastrointestinal effects (nausea, indigestion, vomiting and
diarrhoea or constipation).