Nortriptyline



Nortriptyline 914
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Definition

Nortriptyline is a tricyclic antidepressant. It is sold in the United States under the brand names Aventyl and Pamelor, and is also available under its generic name.

Purpose

Nortriptyline is used to relieve symptoms of depression. The drug is more effective for endogenous depression than for other forms of depression. Endogenous depression is depression arising from metabolic changes within a person, such as chemical or hormonal imbalances. Nortriptyline is also used occasionally to treat premenstrual depression, attention-deficit/hyperactivity disorder in children, and bed-wetting ( enuresis ).

Description

Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain that regulate the transmission of nerve impulses between cells. The precise way in which nortriptyline elevates mood is not fully understood. The drug inhibits the activity of neurotransmitters such as acetylcholine, histamine, and 5-hydroxytryptamine. Studies have indicated that nortriptyline interferes with the release, transport, and storage of catecholamines, another group of chemicals involved in nerve impulse transmission.

Recommended dosage

As with any antidepressant, the dose of nortriptyline must be carefully adjusted by the physician to produce the desired therapeutic effect. Nortriptyline is available in 10-, 25-, 50-, and 75-mg capsules as well as in a 10 mg/5mL solution. The usual dosage for nortriptyline is 25 mg given three or four times each day. The optimum total dose of the drug is 50 to 150 mg daily. Total dosage in excess of 150 mg is not recommended. The recommended dose for older adults (over age 60) and adolescents is 30 to 50 mg per day. Nortriptyline is not recommended for use by children.

The therapeutic effects of nortriptyline, like other tricyclic antidepressants, appear slowly. Maximum benefit is often not evident for two to three weeks after starting the drug. People taking nortriptyline should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.

Once symptoms of depression have been controlled, the lowest dosage that maintains the effect should be taken. People who take 100 mg or more of nortriptyline per day should have their blood tested periodically for nortriptyline concentrations. The results of these tests will show whether the dose is appropriate, too high, or too low.

Precautions

Like all tricyclic antidepressants, nortriptyline should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy, urinary retention, and glaucoma, especially angle-closure glaucoma (the most severe form). Before starting treatment, people with these conditions should discuss the relative risks and benefits of treatment with their doctors to help determine if nortriptyline is the right antidepressant for them.

A common problem with tricyclic antidepressants such as nortriptyline, is sedation (drowsiness, lack of physical and mental alertness). This side effect is especially noticeable early in therapy. In most patients, sedation decreases or disappears entirely with time, but until then, patients taking nortriptyline should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when nortriptyline is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take nortriptyline in combination with these substances.

Nortriptyline may increase the possibility of having seizures . Patients should tell their physician if they have a history of seizures, including seizures brought on by the abuse of drugs or alcohol. These people should use nortriptyline only with caution and be closely monitored by their physician. Nortriptyline can also cause ringing in the ears, tingling in the extremities, and numbness in the extremities, although none of these side effects are common when the drug is used as directed.

When used by people with schizophrenia , nortriptyline may worsen psychotic, increase hostility in some patients, or activate other symptoms that had not previously been expressed. When used by people with bipolar disorder (manic-depressive illness), symptoms of mania may be magnified. Patients with a history of suicide attempts, thoughts of suicide, or drug overdose should be monitored carefully when using nortriptyline. Nortriptyline can either increase or decrease blood sugar levels, depending on the patient and his or her medical condition. Nortriptyline should be used with great caution when a patient is receiving electroconvulsive therapy .

Nortriptyline may increase heart rate and cause irregular heartbeat. It may also raise or lower blood pressure. It may be dangerous for people with cardiovascular disease, especially those who have recently had a heart attack, to take this drug or other antidepressants in the same pharmacological class. In rare cases in which patients with cardiovascular disease must receive nortriptyline, they should be monitored closely for cardiac rhythm disturbances and signs of cardiac stress or damage.

Side effects

Nortriptyline shares side effects common to all tricyclic antidepressants. The most frequent of these are dry mouth, constipation, urinary retention, increased heart rate, sedation, irritability, dizziness, and decreased coordination. As with most side effects associated with tricyclic antidepressants, the intensity is highest at the beginning of therapy and tends to decrease with continued use.

Dry mouth, if severe to the point of causing difficulty speaking or swallowing, may be managed by dosage reduction or temporary discontinuation of the drug. Patients may also chew sugarless gum or suck on sugarless candy in order to increase the flow of saliva. Some artificial saliva products may give temporary relief.

Men with prostate enlargement who take nortriptyline may be especially likely to have problems with urinary retention. Symptoms include having difficulty starting a urine flow and more difficulty than usual passing urine. In most cases, urinary retention is managed with dose reduction or by switching to another type of antidepressant.

Problems associated with the skin (loss of sensation, numbness and tingling, rashes, spots, itching and puffiness), seizures and ringing in the ears have also been reported. Nausea, vomiting, loss of appetite, diarrhea and abdominal cramping are associated with nortriptyline usage. Skin rash, sensitivity to sunlight and itching have been linked to nortriptyline use. People who think they may be experiencing any side effects from this or any other medication should talk to their physicians.

Interactions

Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as nortriptyline, and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Because of this, nortriptyline should never be taken in combination with MAO inhibitors. Patient taking any MAO inhibitors, for example Nardil ( phenelzine sulfate) or Parmate ( tranylcypromine sulfate), should stop the MAO inhibitor then wait at least 14 days before starting nortriptyline or any other tricyclic antidepressant. The same holds true when discontinuing nortriptyline and starting an MAO inhibitor.

Cimetidine (Tagamet) may slow the elimination of nortriptyline, thus effectively increasing the dosage of nortriptyline. Quinidine also raises the circulating levels of the drug, requiring a decrease in the dosage of nortriptyline.

The sedative effects of nortriptyline are increased by other central nervous system depressants such as alcohol, sedatives, sleeping medications, or medications used for other mental disorders such as schizophrenia. The symptoms of increased heart rate, blurred vision, and difficulty urinating are additive with other drugs such as benztropine , biperiden , trihexyphenidyl , and antihistamines.

See also Neurotransmitters

Resources

BOOKS

Adams, Michael, and Norman Holland. Core Concepts in Pharmacology. Philadelphia: Lippincott-Raven, 1998.

Foreman, John C. and Torben Johansen. Textbook of Receptor Pharmacology. 2nd ed. Boca Raton, FL: CRC Press,2002.

Page, Clive P., and Michael Murphy. Integrated Pharmacology. St. Louis: Mosby-Year Book, 2002.

Von Boxtel, Chris J., Budiono Santoso, and I. Ralph Edwards. Drug Benefits and Risks: International Textbook of Clinical Pharmacology. New York: John Wiley and Sons,2001.

PERIODICALS

Mulsant B. H., and others. "A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients." American Journal of Geriatric Psychiatry 9, no. 4 (2001): 406-414.

Nelson J. C. "Diagnosing and treating depression in the elderly." Journal of Clinical Psychiatry 62, Supplement 24(2001): 18-22.

Stolar A. G., and J. T. Stewart. "Nortriptyline for depression and vulvodynia." American Journal of Psychiatry 159, no. 2 (2002): 316-317.

ORGANIZATIONS

American Medical Association. 515 N. State Street, Chicago, IL 60610. Telephone: (312) 464-5000. Web site: <http://www.ama-assn.org/> .

American Psychiatric Association. 1400 K Street NW, Washington, DC 20005. Telephone: (888) 357-7924. Fax(202) 682-6850. Web site: <http://www.psych.org/> .

American Society for Clinical Pharmacology and Therapeutics. 528 North Washington Street, Alexandria, VA 22314. Telephone: (703) 836-6981. Fax: (703) 836-5223.

American Society for Pharmacology and Experimental Therapeutics. 9650 Rockville Pike, Bethesda, MD 20814-3995. Telephone: (301) 530-7060. Fax: (301) 530-7061. Web site: <http://www.aspet.org/> .

L. Fleming Fallon, Jr., M.D., Dr.P.H.



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