Tricyclic antidepressant (TCA)
Inhibits norepinephrine reuptake more selectively than serotonin; also exhibits antagonism at histamine H1 and muscarinic receptors, though to a lesser extent than other TCAs.
Major depressive disorder (MDD)
Neuropathic pain, migraine prophylaxis, insomnia, augmentation in treatment-resistant depression, post-stroke depression (PSD), depression in Parkinson’s disease (PD)
Oral capsules, oral solution
Start at 10–25 mg p.o. nightly; titrate slowly based on clinical response and tolerability
50–150 mg/day; therapeutic plasma level range is typically 50–150 ng/mL
Metabolized primarily via CYP2D6; half-life ~18–44 hours; active metabolite of amitriptyline
Dry mouth, constipation, dizziness, sedation, orthostatic hypotension
Cardiac conduction abnormalities, confusion, seizures, and toxicity in overdose
Therapeutic drug monitoring of serum levels; baseline and periodic ECG in older adults or those with cardiac risk; monitor for anticholinergic burden and falls
Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults
Nortriptyline is often preferred among TCAs in older adults or individuals with neuropsychiatric conditions (e.g., dementia, traumatic brain injury [TBI]) due to its relatively lower anticholinergic and sedating effects. ECG monitoring and serum drug levels may help guide dosing and reduce toxicity in medically complex populations.