Doxepin hydrochloride

Doxepin hydrochloride is a tricyclic antidepressant (TCA) used in the treatment of major depressive disorder, anxiety disorders, chronic hives, and for short-term help with trouble sleeping at low doses. It is a chemical compound that acts by inhibiting the reuptake of neurotransmitters serotonin and norepinephrine, thereby increasing their levels in the central nervous system. Doxepin hydrochloride is known for its sedative effects due to its antagonism of histamine receptors.

Medical Uses

Doxepin hydrochloride is primarily used to treat major depressive disorder, anxiety disorders, and insomnia. It is also effective in treating urticaria (chronic hives) by acting as a potent antihistamine. The medication can be administered in various forms, including oral capsule, liquid, and topical cream.

Mechanism of Action

Doxepin hydrochloride functions by inhibiting the reuptake of serotonin and norepinephrine, two neurotransmitters that play key roles in mood regulation. This inhibition increases the concentration of these neurotransmitters in the synaptic cleft, enhancing their mood-lifting effects. Additionally, doxepin's antagonistic effect on histamine H1 receptors contributes to its sedative and hypnotic properties.

Side Effects

Common side effects of doxepin hydrochloride include drowsiness, dry mouth, blurred vision, constipation, and urinary retention. Due to its sedative properties, it may impair physical and mental abilities, making it hazardous to operate heavy machinery or drive while under its influence. Weight gain and sexual dysfunction are also reported among users. Severe side effects may include an increase in suicidal thoughts or actions, especially in children, adolescents, and young adults.

Contraindications

Doxepin hydrochloride is contraindicated in individuals with a known hypersensitivity to tricyclic antidepressants, those who have recently had a myocardial infarction, and in patients with untreated narrow-angle glaucoma or severe urinary retention. It should be used with caution in individuals with a history of bipolar disorder, as it can induce mania or rapid cycling.

Pharmacokinetics

Doxepin hydrochloride is well absorbed from the gastrointestinal tract but undergoes significant first-pass metabolism, leading to a bioavailability of approximately 13-45%. It is extensively metabolized in the liver, primarily through the cytochrome P450 system, and its metabolites are excreted in the urine. The half-life of doxepin ranges from 8 to 24 hours, which can be prolonged in elderly patients or those with hepatic impairment.

Interactions

Doxepin hydrochloride can interact with a wide range of medications, including other antidepressants, anticholinergic agents, sympathomimetic drugs, and inhibitors of the cytochrome P450 enzyme system. Such interactions can increase the risk of side effects or reduce the efficacy of doxepin or the co-administered drug. Patients should inform their healthcare provider of all medications they are taking to avoid potential drug interactions.

See Also

• Tricyclic antidepressant
• Serotonin-norepinephrine reuptake inhibitor
• Histamine antagonist
• Major depressive disorder
• Anxiety disorder
• Insomnia