What are antipsychotic medications? |

Introduction

Antipsychotic medications were first used to treat people who were out of touch with reality (psychotic) in the 1950s with the development of chlorpromazine (Thorazine).
Originally developed for surgical patients, chlorpromazine was used on patients with psychiatric problems because of its calming effects. Its antipsychotic effect went well beyond calming, as it affected the nervous system, especially the anticholinergic, antidopaminergic, and antihistamine receptors. Chlorpromazine became the model for the class of drugs known as phenothiazines, the early antipsychotics. These and the other early antipsychotics (first-generation antipsychotic agents) are known as typical antipsychotics, or major tranquilizers. At the time that these drugs were developed, people who were deemed psychotic had traditionally been treated with brain surgery (lobotomies), so medications provided a great advance in treatment modalities.

A second class of typical antipsychotics is the phenylbutylpiperadines. This category of drugs includes haloperidol (Haldol), which was first developed in the late 1950s but not approved for use in the United States until 1988. Haloperidol is routinely used to treat delirium and acute psychotic states. It is also used to treat Tourette syndrome. Because of the effect of these drugs on the central nervous system, antipsychotic agents are also referred to as neuroleptics. These drugs can cause a decrease in delusions, hallucinations, confusion, and agitation in psychiatric patients and may normalize their motor activity. Such medications have been widely used to treat disorders such as schizophrenia and bipolar disorder.

In many patients, however, treatment with first-generation antipsychotics has been stopped because of adverse side effects. One set of common side effects is extrapyramidal reactions, including low blood pressure, impotence, lethargy, and tardive dyskinesia (movement disorders involving involuntary, purposeless movements, typically of the face, legs, or torso).

Second-Generation Antipsychotics

To avoid the adverse side effects of the typical antipsychotic agents, medications known as second-generation, or atypical, antipsychotics were developed. The first of these atypical antipsychotics, clozapine (Clozaril), was developed in 1970 (although not approved for use until 1989) and was used for treatment of schizophrenia. This medication, a debenzapine derivative, was found to have a potentially deadly side effect, agranulocytosis (a decrease in the white blood cells circulating in the bloodstream), and was voluntarily withdrawn from the market. In 1989, after further testing, it was approved for use by the Food and Drug Administration for individuals with treatment-resistant schizophrenia.

Another category of second-generation antipsychotics includes the benzisoxidil group, typified by risperidone (Risperdal). This drug is often used to treat bipolar disorder. Each of the atypical antipsychotics also causes side effects, but in general, these drugs are better tolerated than the first-generation antipsychotics.

Use of These Drugs

Typically, when deciding which medication to prescribe, a physician will take into account an individual’s symptoms, age, weight, and personal, family, and medication history. Research has shown that most antipsychotic drugs actually alter the brain’s structure. In some cases, these structural changes are a direct result of the treatment, while in other cases, they are side effects of the medication. Researchers hope that some of these structural changes in the brain may lead to a better understanding of how these antipsychotic drugs work.

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