Doxepin (Dosage)

Doxepin is a tricyclic antidepressant used for the treatment of depression, anxiety and insomnia. Its effectiveness and tolerability are associated with the metabolic activity of cytochromes CYP2D6 and CYP2C19, which are involved in its metabolization, so knowledge of the genetic profile can help in optimal dose adjustment.

Depression is an ongoing mood disturbance with symptoms that include sadness, feelings of worthlessness, loss of interest or pleasure, sleep disturbances, feelings of sluggishness and decreased ability to concentrate.

Doxepin is a drug of the tricyclic antidepressant family used to treat mainly depression and anxiety. It is also used to treat other disorders such as alcoholism or insomnia. Administered topically, it is used to treat itching associated with atopic dermatitis or eczema.


Doxepin belongs to the class of tricyclic antidepressants approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder, anxiety and insomnia, as well as for the control of cutaneous pruritus. Doxepin acts by increasing the concentration of the neurotransmitter serotonin (5-hydroxytryptamine or 5-HT) and norepinephrine (NE) in the brain. This mechanism increases the availability of the neurotransmitters (5-HT and NE) within the synaptic cleft and enhances their neurotransmission by preventing their reuptake at the presynaptic terminal. In addition, it blocks histamine, α1 adrenergic and muscarinic receptors in the central nervous system, and also inhibits sodium and potassium channels in cardiomyocytes, broadening its indication profile. It has also been approved for use in the treatment of insomnia due to its sedative properties.


Doxepin is contraindicated in patients who have previously shown hypersensitivity to this drug or to other dibenzoxepines. It should also be avoided in patients with glaucoma or a tendency to urinary retention.

It is important to keep in mind that significant adverse effects may occur when combined with other medications such as other antidepressants, opiates, alcohol or herbal medicines, among others.

Doxepin is also contraindicated in patients with certain cardiovascular disorders, such as bundle branch block, and in nursing mothers due to its sedative and respiratory depressant effects.


Doxepin can produce adverse effects similar to other tricyclic antidepressants, most of them mild and transient. It produces different side effects depending on the receptor it blocks: histamine H1, adrenergic and muscarinic. By antagonizing the H1 receptor, it can induce sedation and drowsiness, which is why it is used to treat insomnia in patients with depression and anxiety. It can also cause significant weight gain. By blocking α-adrenergic receptors, it can cause orthostatic hypotension, especially in people with cardiovascular problems. Muscarinic receptor antagonism produces anticholinergic effects such as dry mouth, constipation, dizziness, tachycardia and QT interval prolongation. Side effects of topical doxepin include burning and tingling sensations, while its systemic absorption can cause dizziness, dry mouth, blurred vision and headache.


Doxepin is marketed under many trade names, the most common being:

  • Prudoxin®
  • Silenor®
  • Sinequan®
  • Zonalon®

Genes analyzed



Almasi A, Patel P, Meza CE. Doxepin. [Updated 2024 Feb 14] Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

Hicks JK, Swen JJ, Thorn CF, et al. Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants. Clin Pharmacol Ther, 2013; 93(5):402–8.

Hicks JK, Sangkuhl K, Swen JJ, et al. Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update. Clin Pharmacol Ther. 2017 Jul;102(1):37-44.

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