doxepin

Doxepin is a tricyclic antidepressant (TCA) used in the management of major depressive disorder and certain anxiety disorders. It is also prescribed at low doses for the treatment of sleep maintenance insomnia and, in topical form, for pruritus associated with some skin conditions. In some countries, brand-name products are available for these different indications, including oral formulations and a topical cream or patch.

The mechanism of action involves inhibition of the reuptake of norepinephrine and serotonin, increasing their levels in the synaptic cleft. Doxepin also interacts with several receptor systems, including histamine H1, muscarinic, and alpha-adrenergic receptors, which contributes to its sedative effects and a range of anticholinergic side effects.

Doxepin is absorbed from the gastrointestinal tract and is extensively metabolized in the liver to active metabolites, notably nordoxepin. It has a relatively long duration of action and is excreted primarily in the urine. The drug's pharmacokinetic profile supports dosing intervals that reflect its prolonged effects, but individual response and tolerability vary.

Common adverse effects include sedation, drowsiness, dry mouth, constipation, blurred vision, urinary retention, and dizziness. Anticholinergic effects and orthostatic hypotension are notable considerations, particularly in older adults. Doxepin can interact with monoamine oxidase inhibitors and other central nervous system depressants, and it can worsen cardiac conditions in some patients. It is generally avoided in recent myocardial infarction, certain conduction abnormalities, and in individuals with glaucoma or urinary retention. Safety during pregnancy is not established; use only if clearly needed and prescribed by a clinician.