Adults

For neuropathic pain or migraine prophylaxis, initial dose 5-10 mg at bedtime, gradually increasing as tolerated, usually not exceeding 25-50 mg daily. For depression, typically 25 mg three to four times daily, or a single dose at bedtime, up to 150 mg daily.

Elderly

Lower initial dose (e.g., 5-10 mg at bedtime) and slower titration, maximum dose generally lower (e.g., 75 mg daily) due to increased sensitivity to side effects.

Renal_impairment

No specific dosage adjustment recommended, but caution advised due to potential accumulation of metabolites in severe impairment.

Onset

Antidepressant effects may take 2-4 weeks. Analgesic and migraine prophylactic effects may be seen sooner, within days to a couple of weeks.

Excretion

Excreted primarily in urine as metabolites.

Half life

Approximately 16-40 hours.

Absorption

Well absorbed orally; peak plasma concentrations are typically achieved within 2-4 hours.

Metabolism

Extensively metabolized in the liver by cytochrome P450 enzymes, primarily CYP2D6, via hydroxylation, followed by glucuronidation.

MAOIs

Risk of serious, potentially fatal reactions including serotonin syndrome, hyperthermia, rigidity, and cardiovascular collapse.

SSRIs/SNRIs

Increased plasma levels of nortriptyline, increasing the risk of TCA-related side effects. Concurrent use requires caution and dose adjustment.

Anticholinergics

Increased anticholinergic side effects (e.g., severe dry mouth, constipation, urinary retention, blurred vision, delirium).

CNS depressants (alcohol, benzodiazepines)

Enhanced sedative effects and central nervous system depression.

Sympathomimetics (e.g., epinephrine, norepinephrine)

Potentiation of cardiovascular effects.

CYP2D6 inhibitors (e.g., quinidine, fluoxetine, paroxetine)

Significantly increased nortriptyline levels due to reduced metabolism, requiring dose adjustment.