Mechanism of action is unknown. The TCAs are structurally related to the phenothiazine antipsychotic drugs (eg, chlorpromazine), but in contrast to them, TCAs inhibit the presynaptic reuptake of the neurotransmitters norepinephrine and serotonin; anticholinergic at CNS and peripheral receptors; the relation of these effects to clinical efficacy is unknown.

Indications

Relief of symptoms of major depressive disorders

Treatment of OCDs

Unlabeled uses: Treatment of obstructive sleep apnea, panic disorder, eating disorders, PMS, migraine, ADHD, insomnia associated with depression, fibromyalgia, neuropathic pain, adult enuresis

Contraindications and cautions

Contraindicated with hypersensitivity to any tricyclic drug, concomitant therapy with an MAOI, recent MI, myelography within previous 24 hr or scheduled within 48 hr, pregnancy (limb reduction abnormalities reported), or lactation.

Use cautiously with EST; preexisting CV disorders (severe coronary heart disease, progressive heart failure, angina pectoris, paroxysmal tachycardia); angle-closure glaucoma, increased IOP, urine retention, ureteral or urethral spasm; seizure disorders (lower seizure threshold); hyperthyroidism (predisposes to CVS toxicity, including cardiac arrhythmias); impaired hepatic, renal function; psychiatric patients; schizophrenic or paranoid may exhibit a worsening of psychosis; manic-depressive disorder may shift to hypomanic or manic phase; elective surgery (discontinue as long as possible before surgery).

Adverse effects

CNS: Sedation and anticholinergic (atropine-like) effects(dry mouth, blurred vision, disturbance of accommodation for near vision, mydriasis, increased IOP), confusion (especially in elderly), disturbed concentration,hallucinations, disorientation, decreased memory, feelings of unreality, delusions, anxiety, nervousness, restlessness, agitation, panic, insomnia, nightmares, hypomania, mania, exacerba- tion of psychosis, drowsiness, weakness, fatigue, headache, numbness, tingling, paresthesia of extremities, incoordination, motor hyperactivity, akathisia, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms, seizures,speech blockage, dysarthria, tinnitus, altered EEG

CV: Orthostatic hypotension,hypertension, syncope, tachycardia, palpitations, MI, arrhythmias, heart block, precipitation of heart failure, stroke

Endocrine: Elevated or depressed blood sugar; elevated prolactin levels; inappropriate ADH secretion

GI: Dry mouth, constipation, paralytic ileus, nausea,vomiting, anorexia, epigastric distress, diarrhea, flatulence, dysphagia, peculiar taste, increased salivation, stomatitis, glossitis, parotid swelling, abdominal cramps, black “hairy” tongue

GU: Urine retention, delayed micturition, dilation of the urinary tract, gynecomastia, testicular swelling; breast enlargement, menstrual irregularity, and galactorrhea; change in libido; impotence

Hematologic: Bone marrow depression, including agranulocytosis; eosinophilia; purpura; thrombocytopenia; leukopenia

Hypersensitivity: Skin rash, pruritus, vasculitis, petechiae, photosensitization, edema (generalized, face and tongue), drug fever

Withdrawal: Symptoms with abrupt discontinuation of prolonged therapy; nausea, headache, vertigo, nightmares, malaise

Other: Nasal congestion, excessive appetite, weight change; sweating, alopecia, lacrimation, hyperthermia, flushing, chills

Interactions

Drug-drug

Increased TCA levels and pharmacologic effects with cimetidine, fluoxetine, ranitidine

Altered response, including arrhythmias and hypertension, with sympathomimetics

Risk of severe hypertension with clonidine

Hyperpyretic crises, severe seizures, hypertensive episodes, and death with MAOIs

Nursing considerations

Assessment

History: Hypersensitivity to any tricyclic drug; concomitant therapy with an MAOI; recent MI; myelography within previous 24 hr or scheduled within 48 hr; pregnancy; lactation; preexisting disorders; angleclosure glaucoma, increased IOP; urinary retention, ureteral or urethral spasm; seizure disorders; hyperthyroidism; impaired hepatic, renal function; psychiatric, manicdepressivedisorder; elective surgery

Physical: Weight; T; skin color, lesions; orientation, affect, reflexes, vision and hearing; P, BP, orthostatic BP, perfusion; bowel sounds, normal output, liver evaluation; urine flow, normal output; usual sexual function, frequency of menses, breast and scrotal examination; LFTs, urinalysis, CBC, ECG

Interventions

Ensure that depressed and potentially suicidal patients have limited access to drug.

Reduce dosage if minor side effects develop; discontinue drug if serious side effects occur.

Arrange for CBC if patient develops fever, sore throat, or other sign of infection.

Ensure ready access to bathroom if GI effects occur; establish bowel program for constipation.

Provide frequent small meals, frequent mouth care if GI effects occur; provide sugarless candies for dry mouth.

Establish safety precautions if CNS changes occur (side rails, assist walking).

Teaching points

Take these drugs exactly as prescribed; do not stop taking these drugs abruptly or without consulting your health care provider.

Avoid alcohol, sleep-inducing drugs, overthe-counter drugs.

Avoid prolonged exposure to sunlight or sunlamps; use a sunscreen or protective garments if unavoidable.

You may experience these side effects: Headache, dizziness, drowsiness, weakness, blurred vision (reversible; safety measures may be needed if severe; avoid driving or performing tasks requiring alertness); nausea, vomiting, loss of appetite, dry mouth (frequent small meals, mouth care, and sucking sugarless candies may help); nightmares, inability to concentrate, confusion; changes in sexual function.

Report dry mouth, difficulty in urination, excessive sedation.

Representative drugs

amitriptyline

amoxapine

clomipramine

desipramine

doxepin

imipramine

nortriptyline

protriptyline

trimipramine