Amitriptyline (Elavil)

Class

Tricyclic antidepressant (TCA)

Mechanism

Inhibits reuptake of serotonin and norepinephrine, with additional anticholinergic, antihistaminic, and alpha-1 adrenergic blocking effects contributing to clinical profile and side effects.

FDA-Approved Use

Major depressive disorder (MDD).

Off-Label Use

Neuropathic pain, fibromyalgia, insomnia, migraine prophylaxis, irritable bowel syndrome, augmentation in depression and anxiety.

Formulation

Oral tablets.

Titration

10–25 mg p.o. nightly, with slow titration as tolerated.

Dose Range

25–150 mg/day, often lower doses (10–50 mg) effective for pain or sleep.

Kinetics

Metabolized primarily via CYP2D6 and CYP2C19 hepatic enzymes; half-life approximately 10–50 hours depending on metabolic status.

Common AEs

Dry mouth, constipation, urinary retention, sedation, dizziness, orthostatic hypotension, weight gain.

Serious/Rare AEs

Cardiac conduction abnormalities (QT prolongation, arrhythmias), overdose toxicity (potentially fatal).

Monitoring

ECG before initiation in patients over 40 or with cardiac risk factors; monitor for anticholinergic burden, orthostatic hypotension, sedation, and signs of toxicity.

Black Box Warning

Increased risk of suicidal ideation in children, adolescents, and young adults.

Considerations

Use caution in elderly, patients with traumatic brain injury (TBI), dementia, or cognitive impairment due to anticholinergic effects increasing fall and delirium risk. Avoid in patients with cardiac disease without ECG clearance.