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Nortriptyline PharmacologyAntidepressant
IndicationsThe relief of symptoms of depression. Endogenous depressions are more likely to be alleviated than are other depressive states.
ContraindicationsThe concurrent use of nortriptyline or other tricyclic antidepressants with a MAO inhibitor is contraindicated. Hyperpyretic crises, severe convulsions, and fatalities have occurred when similar tricyclic antidepressants were used in such combinations. Discontinue the MAO inhibitor at least 2 weeks before nortriptyline treatment is started. Patients hypersensitive to nortriptyline should not be given the drug.Cross sensitivity between nortriptyline and other dibenzazepines is a possibility. Nortriptyline is contraindicated during the acute recovery period after myocardial infarction.
Warnings Back to top of pagePatients with cardiovascular disease should be given nortriptyline only under close supervision because of the tendency of the drug to produce sinus tachycardia and to prolong the conduction time. Myocardial infarction, arrhythmia, and strokes have occurred. The antihypertensive action of guanethidine and similar agents may be blocked. Because of its anticholinergic activity, use nortriptyline with great caution in patients with glaucoma or a history of urinary retention. Patients with a history of seizures should be followed closely when nortriptyline is administered because this drug is known to lower the convulsive threshold. Great care is required if nortriptyline is administered to hyperthyroid patients or those receiving thyroid medication, because cardiac arrhythmias may develop.Occupational Hazards: Pregnancy and Lactation:
Precautions Back to top of pageThe use of nortriptyline in schizophrenic patients may result in an exacerbation of the psychosis or may activate latent schizophrenic symptoms. If the drug is given to overactive or agitated patients, increased anxiety and agitation may occur. In manic depressive patients, nortriptyline may cause symptoms of the manic phase to emerge.Troublesome patient hostility may be aroused by the use of nortriptyline. Epileptiform seizures may accompany its administration, as may happen with other drugs of its class. Close supervision and careful adjustment of the dosage are required when nortriptyline is used with other anticholinergic drugs and sympathomimetic drugs. Inform the patient that the response to alcohol may be exaggerated. Excessive consumption of alcohol in combination with nortriptyline therapy may have a potentiating effect, which may lead to the danger of increased suicidal attempts or overdosage, especially in patients with histories of emotional disturbances or suicidal ideation. When it is essential, the drug may be administered concurrently with electroconvulsive therapy, although the hazards may be increased. Discontinue the drug for several days, if possible, prior to elective surgery. The possibility of a suicidal attempt by depressed patients remains after the initiation of treatment; in this regard, it is important that the least possible quantity of drug be dispensed at any given time. Both elevation and lowering of blood sugar levels have been reported. A case of significant hypoglycemia has been reported in a Type II diabetic patient maintained on chlorpropamide (250 mg/day) after the addition of nortriptyline (125 mg/day). Drug Interactions: In well-controlled patients undergoing concurrent therapy with cimetidine, a decrease in the steady state serum concentrations of the tricyclic antidepressants may occur when cimetidine therapy is discontinued. The therapeutic efficacy of the tricyclic antidepressant may be compromised in these patients as the cimetidine is discontinued. Several of the tricyclic antidepressants have been cited in these reports. There have been greater than two-fold increases in previously stable plasma levels of other antidepressants including nortriptyline, when fluoxetine has been administered in combination with these agents. Fluoxetine and its active metabolite, norfluoxetine, have a long half-life (7 to 9 days for norfluoxetine) which might affect strategies during conversion from one drug to another. Administration of reserpine during therapy with a tricyclic antidepressant has been shown to produce a stimulating effect in some depressed patients. Close supervision and careful adjustment of the dosage are required when nortriptyline is used with other anticholinergic drugs or sympathomimetic drugs. The patient should be informed that the response to alcohol may be exaggerated. Drugs Metabolized by P450IID6: Concomitant use of tricyclic antidepressants with other drugs metabolized by cytochrome P450IID6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Therefore, co-administration of tricyclic antidepressants with other drugs that are metabolized by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide, and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution.
Adverse Effects Back to top of pageNote:Included in the following list are a few adverse reactions that have not been reported with this specific drug. However, the pharmacologic similarities among the tricyclic antidepressant drugs require that each of these reactions be considered when nortriptyline is administered. Cardiovascular: Psychiatric: Neurologic: Anticholinergic: Allergic: Hematologic: Gastrointestinal: Endocrine; gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; syndrome of inappropriate ADH (antidiuretic hormone) secretion. Other: Withdrawal Symptoms:
Overdose Back to top of pageSymptoms:Overdose of tricyclic antidepressants may be manifest with doses as small as 50 mg in a child. Of patients who are alive at initial presentation, a mortality rate of between 0% and 15% has been reported. Symptoms of overdose of tricyclic antidepressants may begin within several hours of oral ingestion. Symptoms and signs may include blurred vision, confusion, restlessness, dizziness, hypothermia, hyperthermia, agitation, vomiting, hyperactive reflexes, dilated pupils, fever, rapid heart rate, decreased bowel sounds, dry mouth, inability to void, myoclonic jerks, seizures, respiratory depression, myoglobinuric renal failure, nystagmus, ataxia, dysarthria, choreoathetosis, coma, hypotension, and cardiac arrhythmias. An effect on cardiac conduction similar to that of quinidine may be seen with slowing of conduction, prolongation of the QRS complex and QT intervals, right bundle branch and AV block, ventricular tachyarrhythmias (including Torsade de pointes and fibrillation), and death. Prolongation of the QRS duration to more than 0.1 seconds is predictive of more severe toxicity. The absence of sinus tachycardia does not ensure a benign course. Hypotension may be caused by vasodilation, central and peripheral alpha-adrenergic blockade, and cardiac depression. In a healthy young person, prolonged resuscitation may be effective; one patient was reported to survive 5 hours of cardiac massage. Treatment: Ventricular arrhythmias, especially when accompanied by lengthened QRS intervals, may respond to alkalinization by hyperventilation or administration of sodium bicarbonate. It is important to monitor and manage serum electrolyte levels. Refractory arrhythmias may respond to propranolol, bretyllium, or lidocaine. Quinidine and procainamide usually should not be used because they may exacerbate arrhythmias and conduction already slowed by the overdosage. Seizures may respond to diazepam. Phenytoin has pharmacologic properties that may be helpful in dealing with both the seizures and cardiac rhythm disturbances of tricyclic antidepressant overdose. Although the prophylactic use of phenytoin has been suggested, it is not yet of proven value. In some patients, physostigmine may antagonize such effects of tricyclic antidepressant overdose as atrial tachycardia, gut immotility, myoclonic jerks, and somnolence. It is less effective for seizures and ventricular arrhythmias. When giving physostigmine, the patient's condition should be carefully monitored and ventilation and cardiac rhythm should be supported. Cholinergic toxicity from physostigmine may include bronchospasm, bronchorrhea, bradycardia, asystole, diaphoresis, incontinence, and seizures. If physostigmine is used, give it slowly because rapid injection may cause seizures. The effects of physostigmine may be short-lived; repeated doses may lead to continued improvement. Diuresis and dialysis remove little of the tricyclic antidepressant present in the body of a patient who has taken an overdose. Hemoperfusion is of unproven benefit. The patient who has taken a tricyclic overdose should be monitored closely, at least until the QRS duration is normal.
Dosage Back to top of pageNortriptyline is not recommended for children. Nortriptyline is administered orally in the form of capsules. Lower than usual dosages are recommended for elderly patients and adolescents. The use of lower dosages for outpatients is more important than for hospitalized patients who will be treated under close supervision. The physician should initiate dosages at a low level and increase it gradually, checking the clinical response carefully and noting any evidence of intolerance. Following remission, maintenance medication may be required for a long period of time at the lowest dose that will maintain remission. If a patient develops minor side effects, the dosage should be reduced. The drug should be discontinued promptly if adverse effects of a serious nature or allergic manifestations occur.Adults: Geriatrics and Adolescent Patients: Plasma Levels:
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