Doxepin Hydrochloride: Clinical Applications and Pharmacology

Pharmacological Classification and Mechanism of Action

Doxepin hydrochloride is a tricyclic antidepressant (TCA). Its primary mechanism involves the inhibition of norepinephrine and serotonin reuptake in the central nervous system. This action increases the synaptic concentrations of these neurotransmitters, leading to antidepressant effects. It also possesses significant antihistaminic properties, primarily blocking H1 receptors. Additionally, it exhibits anticholinergic effects through antagonism of muscarinic acetylcholine receptors.

Indications and Therapeutic Uses

Doxepin is approved for the management of various conditions. These include depressive disorders, encompassing major depressive disorder and depressive neurosis. Its potent antihistaminic activity also makes it useful in the treatment of pruritus, particularly chronic idiopathic urticaria and atopic dermatitis, offering relief from itching.

Dosage and Administration

The appropriate dosage of doxepin varies depending on the specific condition being treated and individual patient factors. For depressive disorders, treatment typically starts with low doses, gradually increasing as tolerated. For pruritus, lower doses are generally employed, often administered at bedtime due to the drug's sedative effects. Dosage adjustments should be made under the guidance of a healthcare professional.

Adverse Effects and Contraindications

Common adverse effects associated with doxepin include sedation, dry mouth, blurred vision, constipation, urinary retention, and orthostatic hypotension. More serious, but less common, side effects include cardiac arrhythmias and seizures. Doxepin is contraindicated in individuals with known hypersensitivity to TCAs. It should be used with caution in patients with glaucoma, urinary retention, benign prostatic hyperplasia, cardiovascular disease, and seizure disorders. Concomitant use with monoamine oxidase inhibitors (MAOIs) is strictly contraindicated due to the risk of severe adverse reactions, including serotonin syndrome.

Pharmacokinetics and Metabolism

Doxepin is well-absorbed following oral administration. It undergoes extensive hepatic metabolism, primarily via demethylation and hydroxylation. The metabolites, including nordoxepin, may also possess antidepressant activity. Doxepin has a relatively long half-life, typically ranging from 8 to 24 hours. Excretion occurs primarily via the kidneys.

Precautions and Warnings

Due to its sedative effects, doxepin can impair mental and physical abilities required for tasks such as driving or operating machinery. Patients should be cautioned accordingly. Doxepin may potentiate the effects of alcohol and other central nervous system depressants. As with other antidepressants, there is a potential risk of increased suicidal thoughts and behaviors, particularly in children, adolescents, and young adults during the initial stages of treatment. Close monitoring for worsening depression or suicidal ideation is essential.