Tricyclic antidepressant (TCA) / Dibenzoxepin

Doxepin

Sinequan (antidepressant doses), Silenor (ultra-low-dose insomnia)
FDA-Approved Indications
  • Depression (higher doses)
  • Insomnia characterized by difficulty with sleep maintenance (ultra-low dose, 3mg and 6mg -- Silenor)
Common Off-Label Uses
  • Anxiety disorders
  • Chronic pain (neuropathic pain, fibromyalgia)
  • Chronic urticaria/pruritus
  • Insomnia at intermediate doses (10-50mg)
  • Peptic ulcer disease (historical)

Side Effects Worth Knowing

At ultra-low dose (3-6mg): Somnolence/sedation

The intended effect. H1-mediated. Usually mild and appropriate at these doses. Take at bedtime within 30 minutes of sleep. Rarely causes significant next-day sedation at 3mg.

At ultra-low dose (3-6mg): Headache

Reported at rates slightly above placebo in clinical trials. Usually mild and transient.

At ultra-low dose (3-6mg): GI effects

Nausea reported occasionally. Taking on empty stomach is recommended (food delays absorption) but may contribute to mild GI discomfort. The relative absence of clinically significant anticholinergic effects, orthostasis, weight gain, and cardiac effects at these doses is the pharmacological point -- though individual patients may occasionally report mild dry mouth or next-day grogginess.

At antidepressant doses (75-300mg): Sedation

Often profound. H1-mediated. Doxepin is among the most sedating TCAs. Can be therapeutic (insomnia in depressed patients) or limiting (daytime impairment). Tolerance may develop partially.

At antidepressant doses (75-300mg): Anticholinergic effects

Heavy. Dry mouth, constipation, urinary retention, blurred vision, cognitive impairment (especially in elderly), tachycardia. Adds to cumulative anticholinergic burden. Same teaching as chlorpromazine, hydroxyzine, and paroxetine pages.

At antidepressant doses (75-300mg): Orthostatic hypotension

Clinically significant. Alpha-1 blockade. Same mechanism as chlorpromazine and trazodone. Risk of falls, particularly in elderly.

At antidepressant doses (75-300mg): Weight gain

Significant. H1-mediated appetite stimulation with chronic use. Similar to other sedating TCAs (amitriptyline).

At antidepressant doses (75-300mg): Cardiac conduction effects

The critical safety concern. Sodium channel blockade widens QRS. Risk of heart block, ventricular arrhythmias, and death in overdose. Obtain baseline ECG. This is the primary reason TCAs are not first-line antidepressants.

At antidepressant doses (75-300mg): Sexual dysfunction

Serotonergic mechanism. Present at antidepressant doses, as with other serotonergic antidepressants.

At antidepressant doses (75-300mg): Seizure threshold lowering

TCAs lower seizure threshold. Use caution in patients with seizure disorders.

See This Medication in Action

These case studies show how doxepin decisions play out in real clinical scenarios:

Sleep DisordersThe Nurse Who Just Wants to SleepGeriatric PsychiatryThe Retired Teacher Who's ForgettingMood DisordersThe Accountant Whose Medications Aren't WorkingMedication ManagementThe Messy Med ListGeriatric PsychiatryThe Retired Nurse Who Won't Leave Her House

References & Further Reading

This page synthesizes information from standard clinical references. Consult primary sources for all prescribing decisions.

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For learning and board prep — not a prescribing reference. Dosing and safety information change. Always verify against current FDA labeling and your institution’s protocols before prescribing.