Section 06 · Monograph

Nortriptyline

Reviewed Nov 2026FDA label

PamelorTCA

Black Box Warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) in short-term studies of MDD and other psychiatric disorders
Risk must be weighed against clinical need; depression itself is associated with increased suicide risk
Not approved for use in pediatric patients
Patients of all ages should be monitored closely for clinical worsening, suicidality, and unusual changes in behavior, especially during initial months of therapy and at times of dose changes

Relief of symptoms of depression (endogenous depression most likely to respond)FDA-labeled

Neuropathic pain (diabetic peripheral neuropathy, postherpetic neuralgia)Off-label
Migraine and tension-type headache prophylaxisOff-label
FibromyalgiaOff-label
Chronic insomnia (low dose, off-label)Off-label

Tricyclic antidepressant (secondary amine, active metabolite of amitriptyline) that inhibits presynaptic reuptake of norepinephrine and, to a lesser extent, serotonin
For neuropathic pain, thought to enhance descending inhibitory noradrenergic and serotonergic pain pathways in the spinal cord, independent of antidepressant effect, and to modulate sodium channel activity
Also possesses anticholinergic, antihistaminergic, and alpha-1 adrenergic blocking activity

Adults: initiate 25 mg 3-4 times daily (or 25-50 mg/day for neuropathic pain, given once daily at bedtime); increase gradually to usual maintenance of 50-150 mg/day
Maximum recommended dose: 150 mg/day
Elderly: lower starting doses, typically 25-50 mg/day in divided doses
For pain indications (off-label), typical effective doses are lower than antidepressant doses (10-75 mg at bedtime), titrated slowly
Therapeutic drug monitoring recommended when doses exceed 100 mg/day; therapeutic plasma range approximately 50-150 ng/mL
Taper gradually when discontinuing to avoid cholinergic rebound/withdrawal symptoms

Concurrent use of, or use within 14 days of discontinuing, an MAOI, including linezolid and IV methylene blue
Acute recovery phase after myocardial infarction
Known hypersensitivity to nortriptyline or other tricyclic antidepressants

MAOIs: contraindicated — risk of hyperpyretic crisis, severe convulsions, serotonin syndrome
CYP2D6 inhibitors: markedly increase nortriptyline plasma levels and cardiotoxicity risk
Serotonergic agents: increased risk of serotonin syndrome
Anticholinergic drugs: additive anticholinergic effects
CNS depressants and alcohol: additive sedation and respiratory/CNS depression
Sympathomimetics: potentiated pressor response
Class 1C antiarrhythmics and other QT-prolonging drugs: additive cardiac conduction effects

Anticholinergic effects: dry mouth, blurred vision, constipation, urinary retention
Orthostatic hypotension and dizziness
Cardiac conduction abnormalities, arrhythmias, tachycardia (narrow therapeutic index — dangerous in overdose)
Sedation/drowsiness
Weight gain
Confusion, particularly in elderly patients
Tremor and, rarely, lowered seizure threshold
Sexual dysfunction
QT prolongation

Monitor for suicidal ideation and clinical worsening, especially early in treatment
Baseline and periodic ECG, particularly in patients with cardiac disease or those >40 years old
Plasma nortriptyline levels when dosing above 100 mg/day or when toxicity/non-response is suspected
Blood pressure (orthostatic changes) and heart rate
Mental status in elderly patients for confusion/delirium
Signs of anticholinergic toxicity and constipation/urinary retention

Safety not established; animal reproduction data are inconclusive — use only if potential benefit justifies potential risk to the fetus
Limb reduction defects reported anecdotally with TCA exposure; causal relationship not established
Neonates exposed late in pregnancy may show withdrawal symptoms
Excreted in breast milk; use caution and weigh benefits versus risks of infant exposure