Antipsychotic Drugs

Definition

Antipsychotic drugs are a class of medicines used to treat psychosis and other mental and emotional conditions.

Purpose

Psychosis is defined as "a serious mental disorder (as schizophrenia) characterized by defective or lost contact with reality often with hallucinations or delusions." Psychosis is an end-stage condition arising from a variety of possible causes. Anti-psychotic drugs control the symptoms of psychosis, and in many cases are effective in controlling the symptoms of other disorders that may lead to psychosis, including bipolar mood disorder (formerly termed manic-depressive), in which the patient cycles from severe depression to feelings of extreme excitation. This class of drugs is primarily composed of the major tranquilizers; however, lithium carbonate, a drug that is largely specific to bipolar mood disorder, is commonly classified among the antipsychotic agents.

Description

The antipsychotic agents may be divided by chemical class. The phenothiazines are the oldest group, and include chlorpromazine (Thorazine), mesoridazine (Serentil), prochlorperazine (Compazine), and thioridazine (Mellaril). These drugs are essentially similar in action and adverse effects. They may also be used as anti-emetics, although prochlorperazine is the drug most often used for this indication.

Antipsychotic Drugs
Brand Name (Generic Name)	Possible Common Side Effects Include:
Clozaril (clozapine)	Seizures, agranulocytosis, dizziness, increased blood pressure
Compazine (prochlorperazine)	Involuntary muscle spasms, dizziness, jitteriness, puckering of the mouth
Haldol (haloperidol)	Involuntary muscle spasms, blurred vision, dehydration, headache, puckering of the mouth
Mellaril (thioridazine)	Involuntary muscle spasms, constipation and diarrhea, sensitivity to light
Navane (thiothixene)	Involuntary muscle spasms, dry mouth, rash, hives
Risperdal (risperidone)	Involuntary muscle spasms, abdominal and chest pain, fever, headache
Stelazine (trifluopera- zine hydrochloride)	Involuntary muscle spasms, drowsiness, fatigue
Thorazine (chlorpromazine)	Involuntary muscle spasms, labored breathing, fever, puckering of the mouth
Triavil	Involuntary muscle spasms, disorientation, excitability, lightheadedness

The phenylbutylpiperadines are haloperidol (Haldol) and pimozide (Orap). They find primary use in control of Tourette's syndrome. Haloperidol has been extremely useful in controlling aggressive behavior.The debenzapine derivatives, clozapine (Clozaril), loxapine (Loxitane), olanzapine (Zyprexa) and quetiapine (Seroquel), have been effective in controlling psychotic symptoms that have not been responsive to other classes of drugs.The benzisoxidil group is composed of resperidone (Resperidal) and ziprasidone (Geodon). Resperidone has been found useful for controlling bipolar mood disorder, while ziprasidone is used primarily as second-line treatment for schizophrenia.In addition to these drugs, the class of antipsychotic agents includes lithium carbonate (Eskalith, Lithonate), which is used for control of bipolar mood disorder, and thiothixene (Navane), which is used in the treatment of psychosis.

Newer agents

Some newer antipsychotic drugs have been approved by the Food and Drug administration (FDA) in the early 2000s. These drugs are sometimes called second-generation antipsychotics or SGAs. Aripiprazole (Abilify), which is classified as a partial dopaminergic agonist, received FDA approval in August 2003. Two drugs that are still under investigation, a neurokinin antagonist and a serotonin 2A/2C antagonist respectively, show promise in the treatment of schizophrenia and schizoaffective disorder.

Recommended dosage

Dose varies with the drug, condition being treated, and patient response. See specific references.

Key terms

Agranulocytosis — An acute condition marked by severe depression of the bone marrow, which produces white blood cells, and by prostration, chills, swollen neck, and sore throat sometimes with local ulceration. Aalso called agranulocytic angina or granulocytopenia.Anticholinergic — Blocking the action of the neurohormone acetylcholine. The most obvious effects include dry mouth and dry eyes.Anticonvulsants — A class of drugs given to control seizures.Pregnancy category — A system of classifying drugs according to their established risks for use during pregnancy. Category A: Controlled human studies have demonstrated no fetal risk. Category B: Animal studies indicate no fetal risk, but no human studies, or adverse effects in animals, but not in well-controlled human studies. Category C: No adequate human or animal studies, or adverse fetal effects in animal studies, but no available human data. Category D: Evidence of fetal risk, but benefits outweigh risks. Category X: Evidence of fetal risk. Risks outweigh any benefits.

Precautions

Neuroleptic malignant syndrome (NMS). NMS is a rare, idiosyncratic combination of extra-pyramidal symptoms (EPS), hyperthermia, and autonomic disturbance. Onset may be hours to months after drug initiation, but once started, proceeds rapidly over 24 to 72 hours. It is most commonly associated with haloperidol, long-acting fluphenazine, but has occurred with thiothixene, thioridazine, and clozapine, and may occur with other agents. NMS is potentially fatal, and requires intensive symptomatic treatment and immediate discontinuation of neuroleptic treatment. There is no established treatment. Most patients who develop NMS will have the same problem if the drug is restarted.Agranulocytosis has been associated with clozapine. This is a potentially fatal reaction, but can be prevented with careful monitoring of the white blood count. There are no well-established risk factors for developing agranulocytosis, and so all patients treated with this drug must follow the clozapine Patient Management System. For more information, the reader should call 1-800-448-5938.Anticholinergic effects, particularly dry mouth, have been reported with all of the phenothiazines, and can be severe enough to cause patients to discontinue their medication.Photosensitization is a common reaction to chlorpromazine. Patients must be instructed to use precautions when exposed to sunlight.Lithium carbonate commonly causes increased frequency of urination.The so-called atypical antipsychotics are associated with a substantial increase in the risk of developing diabetes mellitus. A study done at the University of Rochester (New York) reported in 2004 that 15.2% of patients receiving atypical antipsychotics developed diabetes, compared with 6.3% of patients taking other antipsychotic medications.Antipsychotic drugs are pregnancy category C. (Clozapine is category B.) The drugs in this class appear to be generally safe for occasional use at low doses during pregnancy, but should be avoided near time of delivery. Although the drugs do not appear to be teratogenic, when used near term, they may cross the placenta and have adverse effects on the newborn infant, including causing involuntary movements. There is no information about safety in breast feeding.As a class, the antipsychotic drugs have a large number of potential side effects, many of them serious. Because of the potential severity of side effects, these drugs must be used with special caution in children. Specific references should be consulted.

Interactions

Because the phenothiazines have anticholinergic effects, they should not be used in combination with other drugs that may have similar effects.Because the drugs in this group may cause hypotension, or low blood pressure, they should be used with extreme care in combination with blood pressure-lowering drugs.The antipsychotic drugs have a large number of drug interactions. Consult specific references.

Resources

Books

Beers, Mark H., MD, and Robert Berkow, MD., editors. "Childhood Psychosis." Section 19, Chapter 274 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.Beers, Mark H., MD, and Robert Berkow, MD., editors. "Psychiatric Emergencies." Section 15, Chapter 194 In The Merck Manual of Diagnosis and Therapy. Whitehouse Station, NJ: Merck Research Laboratories, 2002.Wilson, Billie Ann, Margaret T. Shannon, and Carolyn L. Stang. Nurse's Drug Guide 2003. Upper Saddle River, NJ: Prentice Hall, 2003.

Periodicals

DeLeon, A., N. C. Patel, and M. L. Crismon. "Aripiprazole: A Comprehensive Review of Its Pharmacology, Clinical Efficacy, and Tolerability." Clinical Therapeutics 26 (May 2004): 649-666.Emsley, R., H. J. Turner, J. Schronen, et al. "A Single-Blind, Randomized Trial Comparing Quetiapine and Haloperidol in the Treatment of Tardive Dyskinesia." Journal of Clinical Psychiatry 65 (May 2004): 696-701.Lamberti, J. S., J. F. Crilly, K. Maharaj, et al. "Prevalence of Diabetes Mellitus among Outpatients with Severe Mental Disorders Receiving Atypical Antipsychotic Drugs." Journal of Clinical Psychiatry 65 (May 2004): 702-706.Meltzer, H. Y., L. Arvanitis, D. Bauer, et al. "Placebo-Controlled Evaluation of Four Novel Compounds for the Treatment of Schizophrenia and Schizoaffective Disorder." American Journal of Psychiatry 161 (June 2004): 975-984.Stahl, S. M. "Anticonvulsants as Mood Stabilizers and Adjuncts to Antipsychotics: Valproate, Lamotrigine, Carbamazepine, and Oxcarbazepine and Actions at Voltage-Gated Sodium Channels." Journal of Clinical Psychiatry 65 (June 2004): 738-739.

Organizations

American Society of Health-System Pharmacists (ASHP). 7272 Wisconsin Avenue, Bethesda, MD 20814. (301) 657-3000. http://www.ashp.org.United States Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. (888) INFOFDA. http://www.fda.gov.