Tricyclic antidepressant (TCA)
Inhibits reuptake of serotonin and norepinephrine, with additional anticholinergic, antihistaminic, and alpha-1 adrenergic blocking effects.
Major depressive disorder (MDD).
Neuropathic pain (including neuropathic pain related to multiple sclerosis [MS]), fibromyalgia, insomnia, migraine prophylaxis, agitation and aggression in traumatic brain injury (TBI), irritable bowel syndrome, augmentation in depression and anxiety.
Oral tablets
10–25 mg p.o. nightly, with slow titration as tolerated.
25–150 mg/day, often lower doses (10–50 mg) effective for pain or sleep.
Metabolized primarily via CYP2D6 and CYP2C19 hepatic enzymes; half-life approximately 10–50 hours depending on metabolic status.
Dry mouth, constipation, urinary retention, sedation, dizziness, orthostatic hypotension, weight gain.
Cardiac conduction abnormalities (QT prolongation, arrhythmias), seizure (particularly at higher doses), overdose toxicity (potentially fatal).
ECG before initiation in patients over 40 or with cardiac risk factors; monitor for anticholinergic burden, orthostatic hypotension, sedation, and signs of toxicity.
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders
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.