Imipramine



Imipramine 1043
Photo by: Sebastian Kaulitzki

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Imipramine should be withdrawn gradually, rather than abruptly discontinued.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.



User Contributions:

glory
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Jul 24, 2010 @ 1:13 pm
My brother is using these tablets for six years now,he also takes OLANZAPINE everyday,is it the right dose?.He sleeps alot and stays alone most of the time,,thinking alot!!Will he be better and able to stop using them in future?
Ernest A Joiner
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Jun 13, 2011 @ 3:15 pm
Is your brother being treated for schizophrenia? or is he being treated for depression? Olanzapine is a drug used primarily, if not specifically, for the treatment of schizophrenia. You're gonna need to talk with your brother, if he is capable and willing, enough to know what he told the doctor who prescribed him olanzapine and, due to the vast amount of unecessary details your brother may throw in there, you should probably record this interview on a pocket recorder in case you need to go back and listen to it later. If your brother is willing at all, he may only recant the details once or twice before he gets uncomfortable with any further questioning. He most likely is on medicine for some good reason... if he says he used to think about killing people or torturing animals small animals for any reason but especially for fun, then I suggest that you learn to live with what the doctor has put him on. However... if he says nothing of the sort or only claims that he was hearing "voices"(and so long as the voices were not making him do anything harmfull/illegal to himself or others), then you should catalogue the important parts of what your brother told you and set up a doctor's appointment- whereby you can tag along with your brother. During that appointment and while in the presence of your brother, YOU yourself can directly question the Doctor about your brother's medical conditions and treatment plans. As long as your brother is present and conscious; over 18yrs of age and legally in charge of his own medical decisions; then there are no justifiable reasons for the doctor to deny you information. He may ask your brother if it is okay by him or even have a nurse sit in to witness but, other than that, no well intending doctor is going to deny information to a trusted family member who is interested in helping one of his patients. If he does, I suggest that you help your brother find another doctor- or that you, yourself, consult another doctor as a personal reference.

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