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amitriptyline hydrochloride

Apo-Amitriptyline, Levate (CA), Novotriptyn (CA)

Pharmacologic class: Tricyclic compound

Therapeutic class: Antidepressant

Pregnancy risk category D

FDA Box Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders. Risk is greater during first few months of treatment, and must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family to observe patient closely and communicate with prescriber as needed.

• Drug isn't approved for use in pediatric patients.


Unclear. Inhibits norepinephrine and serotonin reuptake at presynaptic neuron, increasing levels of these neurotransmitters in brain. Also has sedative, anticholinergic, and mild peripheral vasodilating effects.


Tablets: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

Indications and dosages

Depression (often given in conjunction with psychotherapy)

Adults: 75 mg P.O. daily in divided doses; may increase gradually to 150 mg/day. Or start with 50 to 100 mg P.O. at bedtime and increase by 25 to 50 mg as needed, to a total dosage of 150 mg. Hospitalized patients initially may receive 100 mg P.O. daily, with gradual increases as needed to a total dosage of 300 mg P.O.

Dosage adjustment

• Elderly patients

• Adolescents

• Outpatients

Off-label uses

• Analgesic adjunct for phantom limb pain or chronic pain


• Hypersensitivity to drug or other tricyclic antidepressants (TCAs)

• Acute recovery phase after myocardial infarction

• MAO inhibitor use within past 14 days

• Children younger than age 12


Use cautiously in:

• seizures, cardiovascular disease, renal or hepatic impairment, urinary retention, hyperthyroidism, increased intraocular pressure, closed-angle glaucoma, prostatic hypertrophy, bipolar disorder, schizophrenia, paranoia

• elderly patients

• pregnant or breastfeeding patients.


• Administer full dose at bedtime to minimize orthostatic hypotension.

• Don't withdraw drug suddenly. Instead, taper dosage gradually.

• If patient is scheduled for surgery, discuss dosage tapering with prescriber.

• Be aware that drug is often used in conjunction with psychotherapy.

Adverse reactions

CNS: headache, fatigue, agitation, numbness, paresthesia, peripheral neuropathy, weakness, restlessness, panic, anxiety, dizziness, drowsiness, difficulty speaking, excitement, hypomania, psychosis exacerbation, extrapyramidal effects, poor coordination, hallucinations, insomnia, nightmares, seizures, coma, suicidal behavior or ideation (especially in children and adolescents)

CV: ECG changes, tachycardia, hypertension, orthostatic hypotension, arrhythmias, heart block, myocardial infarction

EENT: blurred vision, dry eyes, mydriasis, abnormal visual accommodation, increased intraocular pressure, tinnitus

GI: nausea, vomiting, constipation, dry mouth, epigastric pain, anorexia, paralytic ileus

GU: urinary retention, delayed voiding, urinary tract dilation, gynecomastia

Hematologic: agranulocytosis, thrombocytopenia, thrombocytopenic purpura, leukopenia

Metabolic: changes in blood glucose level

Skin: photosensitivity rash, urticaria, flushing, diaphoresis

Other: increased appetite, weight gain, high fever, edema, hypersensitivity reaction


Drug-drug. Activated charcoal: decreased amitriptyline absorption

Adrenergics, anticholinergics, anticholinergic-like drugs: increased anti-cholinergic effects

Amiodarone, cimetidine, quinidine, ritonavir: increased amitriptyline effects

Barbiturates: decreased amitriptyline blood level, increased CNS and respiratory effects

Clonidine: hypertensive crisis

CNS depressants (including antihistamines, opioids, sedative-hypnotics): increased CNS depression

Drugs metabolized by CYP-4502D6 (such as other antidepressants, phenothiazines, carbamazepine, class 1C antiarrhythmics): decreased amitriptyline clearance, possibly causing toxicity

Guanethidine: antagonism of antihypertensive action

Levodopa: delayed or decreased levodopa absorption, hypertension

MAO inhibitors: hypotension, tachycardia, potentially fatal reactions

Rifabutin, rifampin, rifapentine: decreased amitriptyline blood level and effects

Selective serotonin reuptake inhibitors: increased risk of toxicity

Sympathomimetics: increased pressor effect of direct-acting sympathomimetics (epinephrine, norepinephrine), possibly causing arrhythmias; decreased pressor effect of indirect-acting sympathomimetics (ephedrine, metaraminol)

Drug-diagnostic tests. Eosinophils, liver function tests: increased values Glucose, granulocytes, platelets, white blood cells: increased or decreased levels

Drug-herbs. Angel's trumpet, jimson-weed, scopolia: increased anticholinergic effects

Chamomile, hops, kava, skullcap, valerian: increased CNS depression

St. John's wort: decreased drug blood level and reduced efficacy

Drug-behaviors. Alcohol use: increased CNS sedation

Smoking: increased drug metabolism and altered effects

Sun exposure: increased risk of photo-sensitivity reaction

Patient monitoring

• Evaluate for signs and symptoms of psychosis. If present, discuss possible dosage change with prescriber.

• Assess for changes in patient's mood or mental status.

Monitor for signs and symptoms of depression and assess for suicidal ideation (especially in child or adolescent).

• Check blood pressure for orthostatic hypertension.

• Monitor CBC with white cell differential, glucose levels, and liver function test results.

Patient teaching

Instruct patient, parent, or care-giver to contact prescriber if severe mood changes or suicidal thoughts occur (especially if patient is child or adolescent).

• Tell patient that drug may cause temporary blood pressure decrease if he stands up suddenly. Advise him to rise slowly and carefully.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Inform patient that he'll undergo frequent blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved


Amitriptyline, see there.
McGraw-Hill Concise Dictionary of Modern Medicine. © 2002 by The McGraw-Hill Companies, Inc.