Thioridazine
Thioridazine
Definition
Thioridazine is a potent antianxiety and antipsychotic agent. It is a member of the phenothiazine family of compounds. In the United States thioridazine is sold as under the brand name of Mellaril and is also available under its generic name.
Purpose
Thioridazine is used to manage psychotic disorders. It reduces excitement, abnormal levels of energy, excessive movements (hypermotility), and agitation. The drug is also useful in the short-term treatment of depression that accompanies anxiety, sleep disturbances, agitation, and tension. Thioridazine is used in short-term treatment of children who display seriously inappropriate responses to exciting stimuli.
Description
Thioridazine is used in treating anxiety and psychosis. When used for the treatment of schizophrenia, thioridazine reduces symptoms of emotional withdrawal, anxiety, tension, hallucinations, and suspiciousness. Compared to other phenothiazine drugs, it is less likely to cause vomiting and Parkinson-like symptoms.
It is often successfully used to treat children who have impulsive conduct, difficulty in maintaining attention, show high levels of aggression or have poor tolerance for frustration when other drugs have failed.
Recommended dosage
The dosage of thioridazine must be adjusted to each individual for whom it is prescribed to achieve maximum therapeutic effects and to minimize side effects. The usual initial dosage for adults is 50 to 100 mg three times a day. This may be gradually increased to a maximum of 800 mg per day. Once the desired therapeutic effect has been achieved, the dosage should be stabilized. A typical maintenance dosage is 200 to 800 mg per day, given in three to four doses.
The usual initial dosage for adults being treated for symptoms of anxiety is 25 mg three times per day. After reaching equilibrium and controlling undesired symptoms, the typical maintenance dosage is 20 to 200 mg per day divided into three or four doses.
For children between the ages of two and 12, the usual daily dosage of thioridazine is 0.5 to 3.0 mg per kg of body weight. Severely psychotic children who are hospitalized may receive 25 mg twice each day.
Precautions
It is dangerous to give thioridazine to persons in a comatose state. Seizures due to thioridazine therapy have been reported but are unusual. A sudden decrease in blood pressure due to a change in body position (orthostatic hypotension) with accompanying lightheadedness, may occur in people who have taken the drug. This is more common among women than among men.
Thioridazine increases the level of prolactin, a hormone that stimulates the mammary glands in the breast, in the blood. This is a potential problem for persons with a personal or family history of breast cancer and may increase the risk of breast cancer. For this reason, the benefits and risks of the drug must be carefully evaluated before it is administered.
Long-term use of thioridazine increases the probability of developing tardive dyskinesia (See below). Because of potentially serious side effects, the risks and benefits of thioridazine must be carefully explained and understood before the drug is started.
Side effects
A common side effect of thioridazine is drowsiness and lack of physical and mental alertness. This side effect is especially noticeable early in therapy. Patients taking should refrain from performing hazardous activities requiring mental alertness or coordination. Other common side effects include greater sensitivity to the sun and increased risk of serious sunburn, dry mouth, constipation, and urinary retention. Urinary retention (difficulty starting a urine flow or passing urine,) is a particular problem in men with enlarged prostates.
Thioridazine use may lead to the development of symptoms that resemble Parkinson’s disease, but which are not caused by Parkinson’s. These symptoms may include a taut or mask-like expression on the face, drooling, tremors, pill-rolling motions in the hands, cogwheel rigidity (abnormal rigidity in muscles, characterized by jerky movements when the muscle is passively stretched), and a shuffling gait. Taking anti-Parkinson drugs benztropine mesylate or trihexyphenidyl hydrochloride along with trifluoperazine usually readily controls these symptoms.
Thioridazine has the potential to produce a serious side effect called 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. The incidence of tar-dive dyskinesia increases with increasing age and with increasing dosage of thioridazine. It may also appear after thioridazine use has been discontinues. Women are at greater risk than men for developing tardive dyskinesia. There is no known effective treatment for tardive dyskinesia, although gradual (but rarely complete) improvement may occur over a long period.
An occasionally reported side effect of thioridazine is neuroleptic malignant syndrome. This is a complicated and potentially fatal condition characterized by muscle rigidity, high fever, alterations in mental status, and cardiac symptoms such as irregular pulse or blood pressure, sweating, tachycardia (fast heartbeat), and arrhythmias (irregular heartbeat). People who think they may be experiencing any side effects from this or any other medication should talk to their physician promptly.
Interactions
Thioridazine increases the effect of drugs and substances that depress the central nervous system and. This class of drugs includes anesthetics, opiates, barbiturates,
KEY TERMS
Akathisia —Agitated or restless movement, usually affecting the legs. Movement is accompanied by a sense of discomfort and an inability to sit, stand still, or remain inactive for periods of time. Akathisia is a common side effect of some neuroleptic (antipsychotic) medications.
Dystonia —A neurological disorder characterized by involuntary muscle spasms. The spasms can cause a painful twisting of the body and difficulty walking or moving.
Orthostatic hypotension —A sudden decrease in blood pressure due to a change in body position, as when moving from a sitting to standing position.
Prolactin —A hormone that stimulates milk production and breast development.
Schizophrenia —A severe mental illness in which a person has difficulty distinguishing what is real from what is not real. It is often characterized by hallucinations, delusions, language and communication disturbances, and withdrawal from people and social activities.
Tardive dyskinesia —A condition that involves involuntary movements of the tongue, jaw, mouth or face or other groups of skeletal muscles that usually occurs either late in antipsychotic therapy or even after the therapy is discontinued. It may be irreversible.
atropine, and alcohol. These substances should be avoided or used sparingly by people taking thioridazine.
Propranolol increases the concentration of thioridazine. Concurrent administration of pindolol also increases the concentration of thioridazine. The reverse effect also occurs. Thioridazine increases the concentration of pindolol in the body. Thioridazine may interact with other drugs used to treat mental disorders. People planning to take this drug should review the other medications they are taking with their doctor and pharmacist before starting the drug.
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
Dallaire S. “Thioridazine (Mellaril) and mesoridazine (Serentil): prolongation of the QTc interval.” Canadian Medical Association Journal 164, no 1 (2001): 91-95.
Nelson J. C. “Diagnosing and treating depression in the elderly.” Journal of Clinical Psychiatry 62, Supplement 24 (2001): 18-22.
Pisani F., G. Oteri, C. Costa, G. Di Raimondo, and R. Di Perri. “Effects of psychotropic drugs on seizure threshold.” Drug Safety 25, no. 2 (2002): 91-110.
Ray W. A., S. Meredith, P. B. Thapa, K. G. Meador, K. Hall, and K. T. Murray. “Antipsychotics and the risk of sudden cardiac death.” Archives of General Psychiatry 58, no. 12 (2001): 1161-1167.
Varvel A., E. Vann, E. Wise, D. Philibin, and H. Porter. “Effects of antipsychotic drugs on operant responding after acute and repeated administration.” Psychophar-macology (Berlin) 160, no. 2 (2002): 182-191.
OTHER
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.