Nortriptyline Hydrochloride

Name: Nortriptyline Hydrochloride

Indications

Nortriptyline hydrochloride (nortriptyline hydrochloride (nortriptyline hydrochloride (nortriptyline hydrochloride capsules) capsules) capsules) is indicated for the relief of symptoms of depression. Endogenous depressions are more likely to be alleviated than are other depressive states.

Side effects

Note:

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 the reactions be considered when nortriptyline is administered.

Cardiovascular

- Hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, stroke.

Psychiatric

- Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia, panic, nightmares; hypomania; exacerbation of psychosis.

Neurologic

- Numbness, tingling, paresthesias of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures, alteration in EEG patterns; tinnitus.

Anticholinergic

- Dry mouth and, rarely, associated sublingual adenitis; blurred vision, disturbance of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract. Allergic - Skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (general or of face and tongue), drug fever, cross-sensitivity with other tricyclic drugs.

Hematologic

- Bone marrow depression, including agranulocytosis; eosinophilia; purpura; thrombocytopenia.

Gastrointestinal

- Nausea and vomiting, anorexia, epigastric distress, diarrhea, peculiar taste, stomatitis, abdominal cramps, black-tongue.

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

- Jaundice (simulating obstructive), altered liver function; weight gain or loss; perspiration; flushing; urinary frequency, nocturia; drowsiness, dizziness, weakness, fatigue; headache; parotid swelling; alopecia.

Withdrawal Symptoms

- Though these are not indicative of addiction, abrupt cessation of treatment after prolonged therapy may produce nausea, headache, and malaise.

Overdose

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose, therefore, hospital monitoring is required as soon as possible.

Manifestations

Critical manifestations of overdose include: cardiac dysrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity.

Other signs of overdose may include: confusion, restlessness, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the acute symptoms listed under ADVERSE REACTIONS. There have been reports of patients recovering from nortriptyline overdoses of up to 525 mg.

Management

General

Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. A minimum of six hours of observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient.

Gastrointestinal Decontamination

All patients suspected of tricyclic antidepressant overdose should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage. EMESIS IS CONTRAINDICATED.

Cardiovascular

A maximal limb-lead QRS duration of ≥ 0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. A pH > 7.60 or a pC02 < 20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin. Type 1A and 1 C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning.

CNS

In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center.

Psychiatric Follow-up

Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management

The principles of management of child and adult overdosages are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

Introduction

Tricyclic antidepressant (TCA);a active metabolite of amitriptyline.d

Uses for Nortriptyline Hydrochloride

Major Depressive Disorder

Management of major depressive disorder.a

Results of several studies of TCAs in preadolescent and adolescent patients with major depression indicate lack of overall efficacy in this age group.

Attention Deficit Hyperactivity Disorder

Second-line agent in attention deficit hyperactivity disorder† (ADHD) patients unable to tolerate or unresponsive to stimulants; should be used only under close supervision.b

Associated with a narrower margin of safety than some other therapeutic agents; use only if clearly indicated and with careful monitoring, including baseline and subsequent determinations of ECG and other parameters.

Eating Disorders

Has been used for management of eating disorder† (e.g., bulimia†, anorexia nervosa†) with equivocal results; avoid use in underweight individuals and in those exhibiting suicidal ideation.b

Smoking Cessation

US Public Health Service (USPHS) guideline for the treatment of tobacco use and dependence recommends nortriptyline as a second-line drug for smoking cessation† after first-line drugs (i.e., bupropion [as extended-release tablets], nicotine polacrilex gum or lozenge, transdermal nicotine, nicotine nasal spray, nicotine oral inhaler, varenicline) have been used without success or are contraindicated.104

Bipolar Disorder

Has been used for the short-term management of acute depressive episodes in bipolar disorder†.b e

TCAs associated with a greater risk of precipitating hypomania or manic episodes than other classes of antidepressants;e should always be used in combination with a mood stabilizer (e.g., lithium).e

Schizophrenia

Has been used for the management of acute depressive episodes (in combination with an antipsychotic) in patients with schizophrenia†.b

Anxiety Disorders

Has been used for the management of anxiety† (in combination with anxiolytics, sedatives, or antipsychotics) in patients with depression.b

Postherpetic Neuralgia

Among the drugs of choice for the symptomatic treatment of postherpetic neuralgia†.b

Insomnia

Less effective for insomnia† and associated with more serious adverse reactions than conventional hypnotics.b

Actions

  • Mechanism of action in the management of depression unknown but may involve inhibition of reuptake of norepinephrine and/or serotonin.a b

  • Associated with more frequent anticholinergic, sedative, or cardiovascular effects and weight gain than SSRIs.b

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