Section 02 · Monograph

Amitriptyline

Reviewed Nov 2026FDA label

ElavilTCA

Black Box Warning

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder and other psychiatric disorders.
Anyone considering the use of amitriptyline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.
Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide.
Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
Amitriptyline is not approved for use in pediatric patients.

Relief of symptoms of depression (particularly endogenous depression); tablet formulationFDA-labeled

Migraine prophylaxis (off-label) — commonly used tricyclic antidepressant for chronic and episodic migraine preventionOff-label
Chronic tension-type headache prophylaxis (off-label)Off-label
Neuropathic pain / peripheral neuropathy (off-label)Off-label
Fibromyalgia (off-label)Off-label
Insomnia, low-dose (off-label)Off-label

Tricyclic antidepressant (TCA) that inhibits neuronal reuptake of norepinephrine and serotonin at the synapse, increasing their synaptic concentration and activity
Possesses significant anticholinergic (antimuscarinic) activity
Has sedating antihistaminic (H1) properties
Exact mechanism underlying efficacy in migraine/pain prophylaxis is not fully established but is thought to relate to modulation of central pain-processing pathways distinct from its antidepressant effect

Depression, outpatients: initiate 75 mg/day in divided doses; may increase to 150 mg/day; alternatively, entire dose may be given at bedtime
Depression, hospitalized patients: initiate 100 mg/day, gradually increasing as needed up to 300 mg/day
Adolescent and elderly patients: lower initial doses recommended (e.g., 10 mg three times daily plus 20 mg at bedtime), increased as necessary and tolerated
Maintenance: 50-100 mg/day, may be given as a single bedtime dose
Off-label migraine prophylaxis (not FDA-labeled dosing): typical practice dosing is much lower than antidepressant doses, often started around 10-25 mg at bedtime and titrated gradually — confirm against current guideline sources, as this is not an FDA-approved indication or labeled regimen
Discontinuation: taper gradually rather than abrupt cessation to avoid discontinuation symptoms

Hypersensitivity to amitriptyline or its components
Concurrent use with, or within 14 days of discontinuing, a monoamine oxidase inhibitor (MAOI) — risk of hyperpyretic crisis, severe convulsions, and death
Use with cisapride (risk of QT prolongation)
Acute recovery period after myocardial infarction

MAOIs: contraindicated — risk of hyperpyretic crisis, severe convulsions, and death; requires 14-day washout in either direction
CYP2D6 inhibitors (fluoxetine, paroxetine, quinidine): can markedly increase amitriptyline plasma levels (reported up to several-fold), increasing toxicity risk
Other serotonergic drugs (SSRIs, SNRIs, triptans, tramadol): increased risk of serotonin syndrome
Anticholinergic agents: additive anticholinergic effects (paralytic ileus, hyperpyrexia)
CNS depressants and alcohol: additive sedation and CNS depression
Drugs that prolong QT interval (e.g., cisapride): increased risk of serious cardiac arrhythmia
Guanethidine and similar antihypertensives: amitriptyline may block their antihypertensive effect

Anticholinergic effects: dry mouth, blurred vision, constipation, urinary retention
Orthostatic hypotension and tachycardia
Sedation/drowsiness
Weight gain
Cardiac conduction changes / arrhythmias, especially in overdose or in patients with pre-existing cardiac disease
Confusion, especially in elderly patients
Sexual dysfunction
Rare: seizures, agranulocytosis/leukopenia, angle-closure glaucoma precipitation

Suicidality and clinical worsening, particularly during the first months of therapy and after dose changes
Baseline and periodic ECG in patients with cardiac disease or in older adults, given conduction-slowing and arrhythmia risk
Blood pressure (orthostatic changes)
Anticholinergic burden and cognitive effects in elderly patients
Plasma drug levels if toxicity is suspected or when combined with CYP2D6-interacting drugs
Weight

Pregnancy: teratogenic effects were not observed in standard reproduction studies, but amitriptyline crosses the placenta; available human data are limited — use only if the potential benefit justifies the potential risk to the fetus
Neonates exposed late in pregnancy have had reports of adverse effects including irritability and, rarely, convulsions/withdrawal-type symptoms; discuss risks/benefits with prescriber
Lactation: amitriptyline and its metabolite nortriptyline are excreted into human breast milk; the decision to discontinue nursing or discontinue the drug should take into account the importance of the drug to the mother