Nortriptyline
Nortriptyline
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 to treat premenstrual depression, panic disorders, chronic pain , and some skin conditions. In addition, Nortriptyline is being investigated for the treatment of nicotine dependence.
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 50–150 mg daily. Total dosage in excess of 150 mg is not recommended. The recommended dose for older adults (over age 60) and adolescents is 30–50 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 and lack of physical or 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 physicians 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 physicians. 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 psychosis , 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 patients and their medical conditions. Nortriptyline should be used with great caution when patients are 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 inhibitors (MAOIs). Because of this, nortriptyline should never be taken in combination with MAOIs. Patients taking any MAOIs, for example Nardil (phe-nelzine sulfate) or Parnate (tranylcypromine sulfate), should stop the MAOI, then wait at least 14 days before starting nortriptyline or any other tricyclic anti-depressant. The same holds true when discontinuing nortriptyline and starting an MAOI.
Cimetidine (Tagamet) may slow the elimination of nortriptyline, thus effectively increasing the dosage of nortriptyline. Quinidine also raises the circulating
KEY TERMS
Acetylcholine —A naturally occurring chemical in the body that transmits nerve impulses from cell to cell. Generally, it has opposite effects from dopamine and norepinephrine; it causes blood vessels to dilate, lowers blood pressure, and slows the heartbeat. Central nervous system well-being is dependent on a balance among acetylcholine, dopamine, serotonin, and norepinephrine.
Benign prostate hypertrophy —Enlargement of the prostate gland.
Bipolar syndrome —An abnormal mental condition characterized by periods of intense elation, energy, and activity followed by periods of inactivity and depression.
Catecholamine —A group of neurotransmitters synthesized from the amino acid tyrosine and released by the hypothalamic-pituitary-adrenal system in the brain in response to acute stress. The catechol-amines include dopamine, serotonin, norepinephrine, and epinephrine.
Endogenous depression —Depression arising from causes within a person, such as chemical or hormonal imbalances.
Manic —Referring to mania, a state characterized by excessive activity, excitement, or emotion.
Neurotransmitter —A chemical in the brain that transmits messages between neurons, or nerve cells.
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 , tri-hexyphenidyl , and antihistamines.
See alsoNeurotransmitters.
Resources
BOOKS
Foreman, John C., and Torben Johansen. Textbook of Receptor Pharmacology. 2nd ed. Boca Raton, FL: CRC Press, 2002.
Hall, Sharon M. “Tricyclic Antidepressants in the Treatment of Nicotine Dependence.” Medication Treatmentsfor Nicotine Dependence. ed. Tony P. George. Boca Raton, FL: CRC Press, 2007.
Page, Clive P., and Michael Murphy. Integrated Pharmacology. St. Louis: Mosby-Year Book, 2002.
Preston, John D., John H. O’Neal, and Mary C. Talaga. Handbook of Clinical Psychopharmacology for Therapists. 4th ed. Oakland, CA: New Harbinger Publications, 2004.
PERIODICALS
Foulds, Jonathan, and others. “Developments in Pharma-cotherapy for Tobacco Dependence: Past, Present and Future.” Drug and Alcohol Review 25.1 (Jan. 2006): 59–71.
Hensley, Paula L. “A Review of Bereavement-Related Depression and Complicated Grief.” Psychiatric Annals 36.9 (Sept. 2006): 619–26.
Hughes, John R., Lindsay F. Stead, and Tim Lancaster. “Nortriptyline for Smoking Cessation: A Review.” Nicotine & Tobacco Research 7.4 (Aug. 2005): 491–99.
Mulder, Roger T., and others. “Six Months of Treatment for Depression: Outcome and Predictors of the Course of Illness.” American Journal of Psychiatry 163.1 (Jan. 2006): 95–100.
Shelton, Richard C., and others. “Olanzapine/Fluoxetine Combination for Treatment-Resistant Depression: A Controlled Study of SSRI and Nortriptyline Resistance.” Journal of Clinical Psychiatry 66.10 (Oct. 2005): 1289–97.
Szanto, Katalin, and others. “Emergence, Persistence, and Resolution of Suicidal Ideation During Treatment of Depression in Old Age.” Journal of Affective Disorders 98.1–2 (Feb. 2007): 153–61.
Wagena, E. J., P. Knipschild, and M. P. A. Zeegers. “Should Nortriptyline Be Used as a First-Line Aid to Help Smokers Quit? Results from a Systematic Review and Meta-Analysis.” Addiction 100.3 (Mar. 2005): 317–26.
Wisner, Katherine L., and others. “Postpartum Depression: A Randomized Trial of Sertraline Versus Nortriptyline.” Journal of Clinical Psychopharmacology 26.4 (Aug. 2006): 353–60.
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. Web site: <http://www.psych.org/>
American Society for Clinical Pharmacology and Therapeutics. 528 North Washington Street, Alexandria, VA 22314. Telephone: (703) 836-6981.
American Society for Pharmacology and Experimental Therapeutics. 9650 Rockville Pike, Bethesda, MD 20814-3995. Telephone: (301) 530-7060. Web site: <http://www.aspet.org/>
L. Fleming Fallon, Jr., MD, Dr.P.H.
Ruth A. Wienclaw, PhD
Nortriptyline
Nortriptyline
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.