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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.
• Elderly patients
• 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.
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
• 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.
☞ 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.
Pharmacologic: tricyclic antidepressants
Time/action profile (antidepressant effect)
|PO||2–3 wk (up to 30 days)||2–6 wk||days–wk|
Adverse Reactions/Side Effects
Central nervous system
- suicidal thoughts (life-threatening)
- lethargy (most frequent)
- sedation (most frequent)
Ear, Eye, Nose, Throat
- blurred vision (most frequent)
- dry eyes (most frequent)
- dry mouth (most frequent)
- arrhythmias (life-threatening)
- torsade de pointes (life-threatening)
- hypotension (most frequent)
- ECG changes
- QT interval prolongation
- constipation (most frequent)
- paralytic ileus
- ↑ appetite
- weight gain
- urinary retention
- ↓ libido
- changes in blood glucose
- blood dyscrasias
Drug-Drug interactionAmitriptyline is metabolized in the liver by the cytochrome P450 2D6 enzyme, and its action may be affected by drugs that compete for metabolism by this enzyme, including other antidepressants, phenothiazines, carbamazepine, class 1C antiarrhythmics including propafenone, and flecainide ; when these drugs are used concurrently with amitriptyline, dosage ↓ of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, including cimetidine, quinidine, amiodarone, and ritonavir, may result in ↑ effects of amitriptyline.May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (avoid concurrent use—discontinue 2 wk before starting amitriptyline).Concurrent use with SSRI antidepressants may result in ↑ toxicity and should be avoided (fluoxetine should be stopped 5 wk before starting amitriptyline).Concurrent use with clonidine may result in hypertensive crisis and should be avoided.Concurrent use with levodopa may result in delayed or ↓ absorption of levodopa or hypertension.Blood levels and effects may be ↓ by rifampin, rifapentine, and rifabutin.Concurrent use with moxifloxacin ↑ risk of adverse cardiovascular reactions.↑ CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioids, and sedative/hypnotics.Barbiturates may alter blood levels and effects.Adrenergic and anticholinergic side effects may be ↑ with other agents having anticholinergic properties.Phenothiazines or oral contraceptives ↑ levels and may cause toxicity.Nicotine may ↑ metabolism and alter effects.St. John’s wort may ↓ serum concentrations and efficacy.Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.↑ anticholinergic effects with jimson weed and scopolia.
Availability (generic available)
- Obtain weight and BMI initially and periodically during treatment.
- Assess fasting glucose and cholesterol levels in overweight/obese individuals.
- Monitor BP and pulse before and during initial therapy. Notify health care professional of decreases in BP (10–20 mm Hg) or sudden increase in pulse rate. Patients taking high doses or with a history of cardiovascular disease should have ECG monitored before and periodically during therapy.
- Depression: Monitor mental status (orientation, mood behavior) frequently. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
- Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yrs. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care professional thereafter.
- Pain: Assess intensity, quality, and location of pain periodically during therapy. May require several weeks for effects to be seen. Use pain scale to monitor effectiveness of medication. Assess for sexual dysfunction (decreased libido; erectile dysfunction). Geriatric: Geriatric patients started on amitriptyline may be at an increased risk for falls; start with low dose and monitor closely. Assess for anticholinergic effects (weakness and sedation).
- Lab Test Considerations: Assess leukocyte and differential blood counts, liver function, and serum glucose before and periodically during therapy. May cause an ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be ↑ or ↓.
Potential Nursing DiagnosesIneffective coping (Indications)
Chronic pain (Indications)
Risk for injury (Side Effects)
- Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take weeks to months. May give entire dose at bedtime. Sedative effect may be apparent before antidepressant effect is noted. May require tapering to avoid withdrawal effects.
- Oral: Administer medication with or immediately after a meal to minimize gastric upset. Tablet may be crushed and given with food or fluids.
- Instruct patient to take medication as directed. If a dose is missed, take as soon as possible unless almost time for next dose; if regimen is a single dose at bedtime, do not take in the morning because of side effects. Advise patient that drug effects may not be noticed for at least 2 wk. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability.
- May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
- Orthostatic hypotension, sedation, and confusion are common during early therapy, especially in geriatric patients. Protect patient from falls and advise patient to make position changes slowly. Institute fall precautions. Advise patient to make position changes slowly. Refer as appropriate for nutrition/weight management and medical management.
- Advise patient to avoid alcohol or other CNS depressant drugs during and for 3–7 days after therapy has been discontinued.
- Advise patient, family and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior occur.
- Instruct patient to notify health care professional if urinary retention, dry mouth, or constipation persists. Sugarless candy or gum may diminish dry mouth, and an increase in fluid intake or bulk may prevent constipation. If symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for >2 wk.
- Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions. Alert patient that medication may turn urine blue-green in color.
- Inform patient of need to monitor dietary intake. Increase in appetite may lead to undesired weight gain.
- Advise patient to notify health care professional of medication regimen before treatment or surgery. Medication should be discontinued as long as possible before surgery.
- Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
- Therapy for depression is usually prolonged and should be continued for at least 3 mo to prevent relapse. Emphasize the importance of follow-up exams to monitor effectiveness, side effects, and improved coping skills. Advise patient and family that treatment is not a cure and symptoms can recur after discontinuation of medication.
- Increased sense of well-being.
- Renewed interest in surroundings.
- Increased appetite.
- Improved energy level.
- Improved sleep.
- Decrease in chronic pain symptoms.
- Full therapeutic effects may be seen 2–6 wk after initiating therapy.