amitriptyline

Amitriptyline is a tricyclic antidepressant (TCA) used to treat major depressive disorder and a range of other conditions. In addition to depressive symptoms, it is prescribed for neuropathic pain, migraine prophylaxis, chronic tension-type headaches, and sometimes insomnia or anxiety disorders. It is taken orally, typically once daily at night, with dose adjustments based on response and tolerability.

Pharmacology and mechanism of action: Amitriptyline increases synaptic concentrations of norepinephrine and serotonin by inhibiting their reuptake. It is a tertiary amine TCA with prominent antagonism of muscarinic acetylcholine receptors, histamine H1 receptors, and α1-adrenergic receptors. These effects contribute to both its therapeutic actions and its anticholinergic and sedative side effects. The primary active metabolite is nortriptyline, a secondary amine with its own pharmacologic activity.

Indications and usage: It is approved for major depressive disorder and is used off-label for chronic pain syndromes, including neuropathic pain and fibromyalgia, as well as for migraine prevention in some patients. Due to sedative and anticholinergic properties, it may be chosen when sleep disruption or agitation is present, but this also increases the risk of adverse effects.

Contraindications and precautions: Use is contraindicated in recent myocardial infarction, significant conduction abnormalities, angle-closure glaucoma, urinary retention, and certain mood disorders such as mania. It should not be combined with monoamine oxidase inhibitors and should be used cautiously with alcohol or other CNS depressants. Interactions with other serotonergic drugs can raise the risk of serotonin syndrome, and elderly patients may experience pronounced anticholinergic and cardiovascular effects.

Adverse effects and safety: Common adverse effects include dry mouth, constipation, blurred vision, urinary retention, drowsiness, dizziness, and weight gain. Orthostatic hypotension and tachycardia can occur, and overdose can be dangerous.

Other notes: Amitriptyline is available under several brand names, such as Elavil and Endep, and remains a widely used but carefully monitored option within its therapeutic indications.