Doxepin Therapeutic Cheat Sheet

As dermatologists, pruritus (or itch) is one of the most frequent symptoms that we encounter. The broad spectrum of itch severity in patients with various dermatologic conditions suggests a need for a host of “tools” or medications that dermatologists should have in their toolbox. In this publication, we continue our Therapeutic Cheat Sheet series by highlighting the uses of Doxepin in dermatology, which has been described as one of the most impactful oral and topical medications used in the treatment of recalcitrant, chronic itch related to cutaneous disease.

Doxepin Therapeutic Cheat Sheet

Compiled by: Michael J. Visconti, DO | Reviewed by: David Fivenson, MD, FAAD

Trade Names

Oral: Silenor (U.S.)

Topical: Prudoxin, Zonalon (U.S.)

Drug Class/Mechanism of Action

Tricyclic antidepressant with strong antihistamine (H1 & H2) activity

• • Far superior antihistamine potency compared to diphenhydramine and/or hydroxyzine

Labeled Indications

Oral: Insomnia, Unipolar major depressive disorder

Topical: Moderate pruritus (atopic dermatitis, lichen simplex chronicus)

Off-label Uses

• • Chronic pruritus (including end-stage renal disease, scalp, neurogenic, atopic dermatitis)
  • Urticaria
  • Neurotic excoriations
  • Serum sickness-like reaction pruritus

Dosing (Dermatologic Uses)

Oral:

• • Prolonged half-life
  • 10 to 25 mg per day (QHS recommended)
  • In elderly: initial dosing of < 5 mg with slow dose escalation
  • Intractable disease (without systemic adverse effects) may require as high as 300 mg per day

Topical:

• • 5% cream (45 g tube)

Contraindications

• • Concurrent use with other antidepressants
  • History of mania or bipolar disorder
  • Severe cardiac disease
  • Seizure history

Adverse Effects

Oral:

• • Sedation/drowsiness/somnolence
  • Impaired concentration
  • Orthostatic hypotension
  • Dizziness
  • Anticholinergic effects (dry mouth, dry eyes, increased thirst)
  • Reduced seizure threshold
  • Suicidality

Topical:

• • Allergic contact dermatitis
  • Burning/stinging sensation
  • Sedation/drowsiness

Pregnancy

Oral:

• •  Unclassified

Topical:

• • Category B

Monitoring

• • With higher doses, consider electrocardiograms for cardiac monitoring
  • Monitor for falls and traumatic injuries

Follow up

• • Consider plasma concentration testing for suspected treatment failure (accepted range 150-250 ug/L)
  • Treatment failure may correlate with polymorphisms in CYP450 (CYP2D6) enzymes

References:

1. 1. Drake LA, Millikan LE. The antipruritic effect of 5% doxepin cream in patients with eczematous dermatitis. Arch of Dermatol. 1995;131:1403-1408.
   2. Kouwenhoven TA, van de Kerkhof PCM, Kamsteeg M. Use of oral antidepressants in patients with chronic pruritus: A systematic review. J Am Acad Dermatol. 2017;77:1068-1073.
   3. Chan S, Reddy V, Myers B, et al. High-dose doxepin for the treatment of chronic, intractable scalp pruritus. JAAD Case Rep. 2020;8:71-73.
   4. Beck KM, Yang EJ, Koo J. Dose escalation of doxepin for intractable pruritus. J Am Acad Dermatol. 2018;79.
   5. Gupta MA, Gupta AK. The use of antidepressant drugs in dermatology. J Eur Acad Dermatol and Venereol. 2001;15:512-518.

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