High dose doxepin for the treatment of chronic, intractable
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A 67-year-old man presented with a five-year history of intractable scalp pruritus. He first noticed the abrupt onset of itch and pain on his scalp in 2011. The itch sensation started in the occipital region and spreaded to the rest of his scalp. The severity of itch on a scale of 1 to 10 was often noted between 8 and 10 and was significantly impacting his quality of life. Burning sensations, followed by pruritus, tended to occur in the mornings, worsened during the day, and resolved during the night.

Physical examination was only notable for diffuse mild erythema over the scalp. The patient tried and failed numerous topical, systemic, procedural, and complementary and alternative therapies for his scalp pruritus including oral and topical doxepin, but pruritus did not improve. Additionally, topical clobetasol provided minimal, temporary relief, but never fully addressed his pruritus and burning scalp sensations.

Biopsies of the scalp were consistently negative for folliculitis or a primary inflammatory process. Medical history was significant for history of hypothyroidism and bacterial folliculitis, both of which have been long resolved.

The patient was using topical lidocaine three times per week but he still noted a 10/10 itch severity. He was started on 10 mg of doxepin daily and was gradually titrated to 170 mg daily over eight months. At this dose, he experienced no drowsiness or other side effect but also no benefit and his serum doxepin level was undetectable.

Beyond 170 mg daily, his dose was increased with extra care at the rate of only 10 mg increments every two to four weeks. At 16 months, the patient was up to 280 mg daily. At this point, his serum doxepin level was finally within the target therapeutic range for doxepin’s antidepressant effects, typically between 50 to 250 ng/mL, and at this level the patient reported complete resolution of itch with no side effects.

For the past three years, the patient has continued this regimen of doxepin 280 mg daily and his itch has remained well-controlled and is no longer interfering with his daily life.

Doxepin is a tricyclic antidepressant that is perhaps the most powerful antipruritic agent available to dermatologists, with antihistamine (H1) potency 783- and 56-times greater than that of diphenhydramine and hydroxyzine, respectively.

Source: https://www.jaadcasereports.org/article/S2352-5126(20)30869-9/fulltext?rss=yes