Imipramine
Definition
Imipramine is a tricyclic antidepressant. It is sold under the brand name Tofranil in the United States.
Purpose
Imipramine is used to relieve symptoms of depression.
Imipramine is also used in the treatment of enuresis (bed-wetting) in persons between the ages of six and 25.
Description
Imipramine hydrochloride was the first tricyclic anti-depressant to be discovered. Tricyclic antidepressants act to change the balance of naturally occurring chemicals in the brain called neurotransmitters that regulate the transmission of nerve impulses between cells. Mental well-being is partially dependent on maintaining the correct balance between these brain chemicals. Imipramine is thought to act primarily by increasing the concentration of norepinephrine and serotonin (both chemicals that stimulate nerve cells) and, to a lesser extent, by blocking the action of another brain chemical, acetylcholine. Imipramine shares most of the properties of other tricyclic antidepressants, such as amitriptyline , amoxapine , clomipramine , desipramine , nortriptyline , protriptyline , and trimipramine .
The therapeutic effects of imipramine, like other antidepressants, appear slowly. Maximum benefit is often not evident for two to three weeks after starting the drug. People taking imipramine should be aware of this and continue taking the drug as directed even if they do not see immediate improvement.
Recommended dosage
Imipramine is usually started with a total dosage of up to 100 mg per day divided into several smaller doses. This is generally increased to a total of 200 mg per day divided into several doses. Total dosages for patients who are not hospitalized should be no more than 200 mg per day. The recommended maximum dosage for the drug for all patients is 250 to 300 mg per day. Before dosages greater than 200 mg per day are taken, an electrocardiogram (EKG) should be done. This should be repeated at regular intervals until a steady state dosage is reached. Lower dosages are recommended for adolescents and for people over age 60. The lowest dosage that controls symptoms of depression should be used.
Imipramine should be withdrawn gradually, rather than abruptly discontinued. This will help reduce the possibility of a relapse into depression.
Precautions
Like all tricyclic antidepressants, imipramine should be used cautiously and with close physician supervision in people, especially the elderly, who have benign prostatic hypertrophy (enlarged prostate), 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 imipramine is the right antidepressant for them.
A common problem with tricyclic antidepressants 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 imipramine should not perform hazardous activities requiring mental alertness or coordination. The sedative effect is increased when imipramine is taken with other central nervous system depressants, such as alcoholic beverages, sleeping medications, other sedatives, or antihistamines. It may be dangerous to take imipramine in combination with these substances.
Imipramine may increase heart rate and stress on the heart. 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. Older people and persons with a history of heart disease may develop heart arrhythmias (irregular heartbeat), heart conduction abnormalities, congestive heart failure, heart attack, abnormally rapid heart rates and strokes.
Until a therapeutic dosage has been determined, people starting imipramine should be closely watched for signs of suicide . The risk of suicide is increased when imipramine is taken in overdose or combined with alcohol.
Manic episodes and the emergence of symptoms of pre-existing psychotic states have been reported when imipramine therapy is started.
Side effects
Imipramine 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.
Imipramine usage has been linked to both increases and decreases in blood pressure and heart rate. Heart attacks, congestive heart failure, and strokes have been reported.
Confusion, disorientation, delusions , insomnia , and anxiety have also been reported as side effects in a small percentage of people taking imipramine. 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 all side effects associated with imipramine usage in a small number of people.
Interactions
Methylphenidate may increase the effects of imipramine. This is usually avoided by reducing the dosage of imipramine.
Imipramine may increase the depressant action of alcohol. For this reason, persons taking imipramine should not drink alcoholic beverages.
Dangerously high blood pressure has resulted from the combination of tricyclic antidepressants, such as imipramine, and members of another class of antidepressants known as monoamine oxidase (MAO) inhibitors. Because of this, imipramine should never be taken in combination with MAO inhibitors. Patients 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 imipramine or any other tricyclic antidepressant. The same holds true when discontinuing imipramine and starting an MAO inhibitor.
The sedative effects of imipramine 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 anticholinergic (drying out) effects of imipramine are additive with other anticholinergic drugs such as benztropine , biperiden , trihexyphenidyl , and antihistamines.
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
"Clinical evidence of an interaction between imipramine and acetylsalicylic acid on protein binding in depressed patients." Clinical Neuropharmacology 25, no. 1 (2002): 32-36.
Juarez-Olguin H, H. Jung-Cook, J. Flores-Perez and I. L. Asseff. "Transdermal drug delivery of imipramine hydrochloride. I. Effect of terpenes." Journal of Controlled Release 19; no. 79 (2002): 93-101.
ORGANIZATIONS
American Academy of Clinical Toxicology. 777 East Park Drive, PO Box 8820, Harrisburg, PA 17105-8820. Telephone: (717) 558-7750. Fax: (717) 558-7845. Web site: <http://www.clintox.org/index.html> .
American Academy of Family Physicians. 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. Telephone: (913) 906-6000. Web site: <http://www.aafp.org/> .
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.