TaperCommunitydoxepin
Boxed Warning
Suicidality risk in children, adolescents, and young adults under 25 during initial antidepressant treatment.
Doxepin is a tricyclic antidepressant. At antidepressant doses (75-300mg) it acts on serotonin and norepinephrine. At very low doses (3-6mg, branded Silenor) it acts almost purely as a histamine H1 antagonist for insomnia.
10mg, 25mg, 50mg, 75mg, 100mg, 150mg capsules; 3mg, 6mg tablets (Silenor for insomnia)
Capsules: 10mg, 25mg, 50mg, 75mg, 100mg, 150mg; Tablets (Silenor): 3mg, 6mg; Oral solution: 10mg/mL
Category C
Blocks serotonin and norepinephrine reuptake at high doses; potent histamine H1 antagonism dominates at low doses. Also has muscarinic and alpha-1 effects at antidepressant doses.
For low-dose insomnia use, 1-2 week stepdown is usually adequate. For antidepressant doses, slow hyperbolic taper.
Long-acting metabolite means dose changes take ~2 weeks to fully reflect at steady state — be patient between cuts.
1-3 days after dose reduction
4-10 days
2-4 weeks
Rebound insomnia can persist 2-6 weeks, especially if used long-term for sleep
Toxicity
Toxic in overdose at antidepressant doses — cardiac arrhythmia, seizures, anticholinergic toxicity. Low-dose Silenor much safer in overdose.
Pharmacokinetics
Hepatic via CYP2D6, CYP2C19, CYP1A2 to active nordoxepin.
Renal, primarily as metabolites.
~80%
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