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Doxepin: Uses, Dosage & Side Effects

Doxepin is a tricyclic antidepressant used to treat depression, anxiety disorders, and chronic itching. It has mood-lifting and sedating properties.

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Things worth knowing about "Doxepin"

Doxepin is a tricyclic antidepressant used to treat depression, anxiety disorders, and chronic itching. It has mood-lifting and sedating properties.

What is Doxepin?

Doxepin is a medication belonging to the class of tricyclic antidepressants (TCAs). It has been used in psychiatry and dermatology since the 1960s and is one of the longest-established antidepressants available. Doxepin is available in several formulations, including tablets, capsules, oral drops, and a topical cream for the treatment of itching.

Indications (Uses)

Doxepin is prescribed for the following conditions:

Depression: Treatment of depressive episodes, particularly when accompanied by anxiety or sleep disturbances
Anxiety disorders: Generalized anxiety disorder and mixed states of depression and anxiety
Chronic pruritus (itching): Especially in atopic dermatitis and other chronic inflammatory skin conditions (topical use)
Insomnia: At low doses for the treatment of difficulty falling or staying asleep

Mechanism of Action

Doxepin works through several simultaneous mechanisms, which is characteristic of tricyclic antidepressants:

Inhibition of serotonin and noradrenaline reuptake: Doxepin blocks the transporters that carry serotonin and noradrenaline back into nerve cells, allowing these neurotransmitters to remain active longer and improving mood.
Antihistamine effect: Doxepin is a highly potent blocker of histamine H1 and H2 receptors. This accounts for its strong sedating effect and its effectiveness in relieving itching.
Anticholinergic effect: Blockade of muscarinic receptors, which leads to side effects such as dry mouth.
Alpha-adrenolytic effect: Blockade of alpha-1 adrenoceptors, which can cause a drop in blood pressure.

Dosage

The dosage of doxepin depends on the indication and the individual response of the patient:

Depression and anxiety disorders: Typically 75–150 mg per day, divided into several doses or taken as a single dose in the evening. In severe cases, up to 300 mg daily may be prescribed.
Insomnia: Low doses of 3–6 mg at bedtime (in specifically approved low-dose formulations).
Topical use (cream): Doxepin cream (5%) is applied thinly to the affected skin areas, usually 3–4 times per day.

Dosage should always be determined individually by a physician and increased gradually.

Side Effects

Like all tricyclic antidepressants, doxepin can cause a range of side effects:

Common Side Effects

Dry mouth
Drowsiness and sedation
Weight gain
Constipation
Blurred vision
Dizziness and low blood pressure upon standing (orthostatic hypotension)

Rare but Serious Side Effects

Cardiac arrhythmias (QT interval prolongation)
Urinary retention
Confusion, especially in elderly patients
Lowered seizure threshold
Triggering of a manic episode in patients with bipolar disorder

Contraindications

Doxepin must not be used in patients with:

Narrow-angle glaucoma (increased intraocular pressure)
Urinary retention
Concurrent use of MAO inhibitors
Acute myocardial infarction or severe cardiac arrhythmias
Hypersensitivity to doxepin or other tricyclic antidepressants

Drug Interactions

Doxepin can interact with a number of other medications:

MAO inhibitors: Potentially life-threatening combinations; a gap of at least 14 days must be observed.
Other CNS depressants (e.g., alcohol, benzodiazepines): Enhanced sedation.
Antiarrhythmic drugs: Increased risk of cardiac arrhythmias.
CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase doxepin plasma levels.

Important Usage Notes

Doxepin should not be stopped abruptly, as this can cause discontinuation symptoms such as nausea, insomnia, and irritability. Treatment should always be tapered gradually under medical supervision. Alcohol should be avoided during treatment. Because doxepin can impair the ability to drive or operate machinery, patients should exercise particular caution in these activities.

References

Stahl SM. Stahl's Essential Psychopharmacology. 4th edition. Cambridge University Press, 2013.
Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 13th edition. McGraw-Hill, 2018.
National Institutes of Health (NIH) - MedlinePlus. Doxepin. Available at: https://medlineplus.gov/druginfo/meds/a682390.html

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