Chlorpromazine
Definition
Chlorpromazine is an antipsychotic drug. It is a member of the phenothiazine family of compounds and is used to alleviate the symptoms and signs of psychosis . Psychosis is a form of severe mental illness, which is characterized by loss of contact with reality, hallucinations , delusions , agitation, and unusual behavior. In the United States, chlorpromazine is also sold under the brand name Thorazine.
Purpose
Chlorpromazine is principally used to reduce the signs and symptoms of psychosis. For this purpose, the drug is used in schizophrenia and the manic phase of bipolar (formerly manic-depressive) disorder. The drug is also used in the management of severe behavioral disorders with aggression, combativeness, or excessive excitability. Chlorpromazine may sometimes be used as a sedative in non-psychotic patients with excessive anxiety and agitation. In addition, the drug has been used to relieve nausea, vomiting, and persistent hiccups.
Description
Chlorpromazine was the first antipsychotic drug. It is not an exaggeration to say that the development of this medication began a revolution in the treatment of severe mental illness, which continues to this day. Patients with schizophrenia and other psychoses, who once would have been considered hopelessly untreatable and relegated to the back wards of state institutions, are often able today, as a result of treatment with chlorpromazine or similar medications, to live in the community and lead fuller lives.
The discovery of chlorpromazine resulted from efforts of pharmaceutical researchers in the first half of the twentieth century to develop sedative medications. Several drugs of a chemical class known as phenothiazines were investigated and shown to be effective sedatives, but they had little effect on agitated patients with psychosis. A new phenothiazine drug, chlorpromazine, was synthesized in France in 1950 and was tested on such patients. In 1952, two French psychiatrists, Delay and Deniker, announced that the drug exerted a specific effect in diminishing the symptoms and signs of psychosis in patients with severe mental illnesses.
The mechanism of action of chlorpromazine is not completely understood. Its antipsychotic effects are believed to be related to its action in selectively blocking the transmission of nerve impulses from cell to cell in a region of the brain called the limbic system. This part of the brain is involved with emotions and motivation.
Chlorpromazine, when sold under the name Thorazine, is available in many forms: tablets of 10, 25, 50, 100, and 200 mg; spansules (sustained release capsules) of 30, 75, and 150 mg; ampules for injection of 25 and 50 mg; multidose vial of 10 mL of 25 mg/mL; syrup 10mg/5mL, 4 fl oz.; suppositories of 25 and 100 mg. Generic chlorpromazine manufacturers may supply a somewhat different set of dosages and products.
Recommended dosage
For acutely disturbed adult patients suffering from a psychosis, such as schizophrenia or mania, the usual daily dosage ranges from 100 mg to 1000 mg per day. Some patients may require a higher dosage. There is great variation in individual dosage requirements for chlorpromazine and for other antipsychotic medications. It is usually advisable to begin with a lower dosage, and increase the dosage until sufficient reduction of symptoms is achieved. Maximum reduction of symptoms may take many weeks of continued treatment. Because of the possibility of side effects, which may be severe, lower dosages should be used in outpatients, children, the elderly, and patients with serious health problems. For non-psychotic patients with excessive anxiety or agitation, amounts used are generally less than 200 mg per day, divided among two or three doses.
For nausea and vomiting in adults, the usual dosage is 10–25 mg every four to six hours as needed, given by injection. Alternatively, doses of 50–100 mg may be given rectally. Persistent hiccups may be treated with 25–50 mg three or four times per day, orally or by injection.
Precautions
Elderly patients (those over age 65), especially women, and patients receiving long-term antipsychotic treatment are prone to develop tardive dyskinesia . This syndrome consists of involuntary, uncoordinated movements that may not disappear or may only partially improve after the drug is stopped. Tardive dyskinesia involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles. Tardive dyskinesia may also appear after chlorpromazine use has stopped. There is no known effective treatment for tardive dyskinesia, although gradual (but rarely complete) improvement may occur over a long period. The need for long-term antipsychotic medication should be weighed against the risk of tardive dyskinesia, which increases with duration of treatment.
Neuroleptic malignant syndrome (NMS), a dangerous condition with high fever, muscular rigidity, rapid pulse, sweating, and altered mental state, may occur with antipsychotic medication. NMS requires immediate medical treatment.
Phenothiazine drugs, such as chlorpromazine, may cause sedation and may interfere with driving and other tasks requiring alertness. They may increase the effects of alcohol and sedatives. The adverse effects of chlorpromazine may be increased in people with diseases of the heart, liver, or kidney, or other debilitating illnesses. Phenothiazines may lower the seizure threshold, making it more likely that a seizure will occur in people who have a history of seizures . People with epilepsy may require adjustment of their anti-seizure medications. Chlorpromazine may cause acute muscle spasms, particularly of the head and neck, and sudden decreases of blood pressure. Patients may need to be hospitalized during the initial phase of treatment, particularly when receiving high doses or treatment by injection.
Chlorpromazine reduces the body's ability to sweat, thus interfering with the regulation of body temperature. This may be a problem for some people in very hot weather. The problem most commonly occurs in elderly people in hot buildings without air conditioning. Body temperature may reach fatal levels. People taking chlorpromazine should be aware of the possibility of developing hyperthermia (high body temperature) in very hot weather. They should seek cool places in very hot weather.
Children may especially susceptible to neurologic reactions to phenothiazines, such as muscle spasms. Elderly patients may be particularly sensitive to sedation, low blood pressure, and other side effects. These patients should start with lower doses and increase their dosage gradually under physician supervision. Chlorpromazine may decrease salivation in older patients, predisposing to tooth decay, gum disease and mouth infections. Candy and other sugary foods should be limited, and oral hygiene should be maintained.
Chlorpromazine, like all phenothiazines, should not be taken by pregnant women because they harm the developing fetus. Breast-feeding is not recommended while taking the drug. Phenothiazines are secreted in breast milk and may cause harm to nursing infants.
Side effects
Chlorpromazine and other phenothiazines may cause many side effects. The following more common side effects are grouped by the body system affected:
- Cardiovascular: decreases of blood pressure, especially on arising, which may cause dizziness or fainting; rapid heart rate, changes in heart rhythm and electrocardiogram.
- Nervous system: sedation, muscle spasms of the head and neck, muscle rigidity, restlessness, tremors, slowed movement, shuffling gait, increased seizure tendency.
- Digestive system: dry mouth, nausea, constipation, abnormal liver tests.
- Autonomic: blurred vision, nasal congestion, reduced sweating, difficulty urinating, problems with ejaculation, impotence.
- Hormonal: lactation, breast enlargement.
- Skin: rashes, sensitivity to sunlight.
- Body as a whole: weight gain.
Interactions
Chlorpromazine interacts with a long list of other medications. Anyone starting this drug should review the other medications they are taking with their physician and pharmacist for possible interactions. Chlorpromazine and other phenothiazines may intensify the effects of drugs causing sedation, including alcohol, barbiturates , narcotic pain medications, minor tranquilizers, and antihistamines. Similarly, chlorpromazine may cause excessive reductions of blood pressure in patients taking other medicines that lower blood pressure. Chlorpromazine may also intensify side effects of drugs that also cause blurred vision, dry mouth, diminished sweating in hot weather, and constipation. Many other antipsychotics and antidepressants cause such effects.
Chlorpromazine may enhance the effects of medications that lower the seizure threshold, such as steroid drugs, the asthma medication theophylline, and many other psychiatric drugs. Patients with epilepsy may require dosage adjustments of their anti-seizure medications. The effectiveness of medications for Parkinson's disease may be reduced by chlorpromazine and other antipsychotics. The likelihood of changes in heart rhythm may be increased when the drug is taken with other medications that have the same effect, including other antipsychotic drugs, antidepressants, certain heart medicines, and erythromycin.
Certain drugs that are eliminated by the liver may interfere with the elimination of chlorpromazine from the body, causing higher blood levels and increased side effects. Chlorpromazine may retard the elimination of other medicines, including many antidepressants, antipsychotic drugs, and heart medications, resulting in higher levels of these other medications and possibly increased side effects.
Resources
BOOKS
American Society of Health-System Pharmacists, Inc. AHFS Drug Information, edited by Gerald K. McEvoy, Pharm.D. Bethesda, MD: American Society of Health-System Pharmacists, Inc., 2001.
Medical Economics Staff. Physicians' Desk Reference. 55th ed. Montvale, NJ: Medical Economics Company, Inc., 2001.
Nissen, David, ed. Mosby's GenRx 11th ed. St. Louis: Mosby, Inc., 2001.
The United States Pharmacopeial Convention, Inc. USP DI(r) Volume I–. Drug Information for the Health Care Professional. 21st ed. Englewood, CO: Micromedex, Inc., 2001.
The United States Pharmacopeial Convention, Inc. USP DI(r) Volume II–. Advice for the Patient. 21st ed. Englewood, CO: Micromedex, Inc., 2001.
Richard Kapit, M.D.
