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Generic Name: DoxepinTrade names: Silenor, Prudoxin, ZonalonDrug Class: Tricyclic antidepressant (TCA), Topical Skin ProductsDoxepine is in the tricyclic antidepressant class of medications and was approved by the FDA in 1969 for the treatment of major depressive disorder (Myers et al., 2022). In addition to its use for the management of depression, it has also shown efficacy with anxiety, insomnia, and pruritis associated with skin conditions such as atopic dermatitis and lichen complex chronicus (Almasi & Meza, 2022). In treating depression, doxepin increases the concentration of serotonin and norepinephrine in the synaptic cleft by preventing the reuptake of these neurotransmitters (Almasi & Meza, 2022).  Doxepin is also an antagonist of the alpha-adrenergic, muscarinic, and histamine (H1 and H2) receptors, making it potentially effective for multiple conditions. Systemic delivery of doxepin is currently FDA-approved for treating depression, anxiety, and insomnia. The topical formulation also has FDA-approval to treat pruritis. Off-label uses include migraine prophylaxis, chronic skin conditions, and neuropathic pain (Myers et al., 2022). Methods of delivery are as oral tablets (3 mg and 6 mg), oral capsules (10 mg, 25 mg, 50 mg, 75 mg, 100 mg, and 150 mg), and oral solutions (10 mg/mL) (Almasi & Meza, 2022).  Transbuccal delivery continues to be studied. Typical dosing for depression is 75-150 mg PO daily and 10-25 mg per day for pruritis (Myers et al., 2022). In targeting multiple receptors, doxepin’s side effects can be anticholinergic with conditions such as blurred vision, dry mouth, and urinary retention. Side effects may also be related to antihistamine effects such as sedation or anti-alpha-1-adrenergic in nature with postural hypotension (Myers et al., 2022).

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