Tricyclic antidepressant (TCA)
Inhibits reuptake of serotonin and norepinephrine; at lower doses, acts as a potent H1 histamine receptor antagonist with minimal anticholinergic effects.
Major depressive disorder (MDD), anxiety disorders, insomnia (low-dose formulation for sleep maintenance).
Chronic urticaria, pruritus, post-traumatic stress disorder (PTSD), augmentation in depression, post-stroke depression (PSD)
Oral tablets, capsules, solution; low-dose formulation (Silenor) for insomnia.
For depression/anxiety, 25–50 mg p.o. daily, divided BID or taken at bedtime; titrate to 75–300 mg/day as tolerated. For insomnia, 3–6 mg nightly (FDA-approved) or off-label 10–25 mg p.o. nightly.
75–300 mg/day for mood and anxiety; 3–25 mg/day for sleep or pruritus.
Metabolized by CYP2C19 and CYP2D6; half-life 8–24 hours depending on dose and formulation.
Sedation, dry mouth, constipation, blurred vision, dizziness, weight gain.
Cardiac arrhythmias, orthostatic hypotension, urinary retention, cognitive impairment, overdose toxicity.
Baseline ECG in patients over 40 or with cardiac risk factors; monitor orthostasis and anticholinergic burden.
Increased risk of suicidal ideation in children, adolescents, and young adults.
Low-dose doxepin is often better tolerated in older adults with insomnia due to reduced anticholinergic effects. Higher doses should be avoided in patients with dementia, traumatic brain injury (TBI), or significant cognitive impairment due to sedation, fall risk, and delirium potential. ECG monitoring is advised in older or cardiac patients before initiating high-dose therapy.