Antipsychotic Drugs, Atypical

Definition

The atypical antipsychotic agents, sometimes called the "novel" antipsychotic agents are a group of drugs which are different chemically from the older drugs used to treat psychosis. The "conventional" antipsychotic drugs are classified by their chemical structures as the phenothiazines, thioxanthines (which are chemically very similar to the phenothiazines), butyrophenones, diphenylbutylpiperadines and the indolones. All of the atypical antipsychotic agents are chemically classified as dibenzepines. They are considered atypical or novel because they have different side effects from the conventional antipsychotic agents. The atypical drugs are far less likely to cause extra-pyrammidal side-effects(EPS), drug induced involuntary movements, than are the older drugs. The atypical antipsychotic drugs may also be effective in some cases that are resistant to older drugs.

The drugs in this group are clozapine (Clozaril), loxapine (Loxitane), olanzapine (Zyprexa), and quetiapine (Seroquel).

Purpose

The antipsychotic drugs are used to treat severe emotional disorders. Although there may be different names for these disorders, depending on severity and how long the symptoms last, psychotic disorders all cause at least one of the following symptoms:

Loxapine has also been used to treat anxiety with mental depression.

Recommended dosage

The recommended dose depends on the drug, the patient, and the condition being treated. The normal practice is to start each patient at a low dose, and gradually increase the dose until a satisfactory response is achieved. The odse should be held at the lowest level that gives satisfactory results.

Clozapine usually requires doses between 300 and 600 milligrams a day, but some people require as much as 900 milligrams/day. Doses higher than 900 millgrams/day are not recommended.

Loxapine is usually effective at doses of 60-100 milligrams/day, but may be used in doses as high as 250 mg/day if needed.

Olanzapine doses vary with the condition being treated. The usual maximum dose is 20 milligrams/day.

Quetiapine may be dosed anywhere from 150-750 milligrams/day, depending on how well the patient responds.

Precautions

Although the atypical antipsychotics are generally safe, clozapine has been associated with severe agranulocytosis, a shortage of white blood cells. For this reason, people who may be treated with clozapine should have blood counts before starting the drug, blood counts every week for as long as they are using clozapine, and blood counts every week for the first 4 weeks after they stop taking clozapine. If there is any evidence of a drop in the white blood count while using clozapine, the drug should be stopped.

Atypical antipsychotics should not be used in patients with liver damage, brain or circulatory problems, or some types of blood problems.

KEY TERMS

Anxiety— An abnormal and overwhelming sense of apprehension and fear often marked by physiological signs (as sweating, tension, and increased pulse), by doubt concerning the reality and nature of the threat, and by self-doubt about one's capacity to cope with it.

Delusions— A false belief regarding the self or persons or objects outside the self that persists despite the facts.

Depression— A state of being depressed marked especially by sadness, inactivity, difficulty with thinking and concentration, a significant increase or decrease in appetite and time spent sleeping, feelings of dejection and hopelessness, and sometimes suicidal thoughts or an attempt to commit suicide.

Glucocorticoid— Any of a group of corticosteroids (as hydrocortisone or dexamethasone) that are anti-inflammatory and immunosuppressive, and that are used widely in medicine (as in the alleviation of the symptoms of rheumatoid arthritis).

Psychosis— A serious mental disorder characterized by defective or lost contact with reality often with hallucinations or delusions.

Allergies

People who have had an allergic reaction to one of the atypical antipsychotics should not use that medication again. However, sometimes it is possible to use a different drug from the same group safely.

Pregnancy

The atypical antipsychotics have not been proved safe in pregnancy. They should be used only when clearly needed and when potential benefits outweigh potential hazards to the fetus. These drugs have not been reported in human milk.

Side effects

Although the atypical antipsychotics are less likely to cause involuntary movements than the older antipsychotic drugs, they still have a large number of adverse effects. The following list is not complete. Review each drug individually for a full list of possible adverse effects.

Interactions

Taking atypical antipsychotic medications with certain other drugs may affect the way the drugs work or may increase the chance of side effects. While taking antipsychotic drugs, do not take any other prescription or nonprescription (over-the-counter) drugs without first checking with a physician.

Because the atypical antipsychotics may cause lowering of blood pressure, care should be used when these drugs are taken at the same time as other drugs which lower blood pressure.

Quetiapine has many interactions. Doses should be carefully adjusted when quetiapine is used with ketoconazole, itraconazole, fluconazole, erythromycin, carbamazepine, barbiturates, rifampin or glucocorticoids including prednisone, dexamethasone and methylprednisolone.

These drugs will also require dose adjustments when used with anti-Parkinson medications.

Resources

BOOKS

Brain Basics: An Integrated Biological Approach to Understanding and Assessing Human Behavior. Phoenix: Biological-Psychiatry-Institute, June 1999.

PERIODICALS

McDougle, C. J. "A double-blind, placebo-controlled study of risperidone addition in serotonin reuptake inhibitor-refractory obsessive-compulsive disorder." Archives of General Psychiatry August 2000: 794.