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A 19-year-old male student is brought into the clinic by his mother, who has been concerned about her son’s erratic behavior and strange beliefs.* He destroyed a TV because he felt the TV was sending harassing messages to him. In addition, he reports hearing voices telling him that family members are trying to poison his food. As a result, he is not eating. After a diagnosis is made, haloperidol is prescribed at a gradually increasing dose on an outpatient basis. The drug improves the patient’s positive symptoms but ultimately causes intolerable adverse effects including severe akathisia. Although more costly, lurasidone is then prescribed, which, over the course of several weeks of treatment, improves his symptoms and is tolerated by the patient. What signs and symptoms would support an initial diagnosis of schizophrenia? In the treatment of schizophrenia, what benefits do the second-generation antipsychotic drugs offer over the traditional agents such as haloperidol? In addition to the management of schizophrenia, what other clinical indications warrant consideration of the use of drugs nominally classified as antipsychotics?

*The author thanks Herbert Meltzer, MD, PhD, for his contributions to prior editions of this chapter.


Antipsychotic drugs are able to reduce psychotic symptoms in a wide variety of conditions, including schizophrenia, bipolar disorder, psychotic depression, psychoses associated with dementia, and drug-induced psychoses. They are also able to improve mood and reduce anxiety and sleep disturbances, but they are not the treatment of choice when these symptoms are the primary disturbance in nonpsychotic patients. A neuroleptic is a subtype of antipsychotic drug that produces a high incidence of extrapyramidal side effects (EPS) at clinically effective doses, or catalepsy in laboratory animals. The second-generation or “atypical” antipsychotic drugs are now the most widely used type of antipsychotic drug.


Reserpine and chlorpromazine were the first drugs found to be useful to reduce psychotic symptoms in schizophrenia. Reserpine was used only briefly for this purpose and is no longer of interest as an antipsychotic agent. Chlorpromazine is a neuroleptic agent; that is, it produces catalepsy in rodents and EPS in humans. The discovery that its antipsychotic action was related to dopamine (D or DA)-receptor blockade led to the identification of other compounds as antipsychotics between the 1950s and 1970s. The discovery of clozapine in 1959 led to the realization that antipsychotic drugs need not cause EPS in humans at clinically effective doses. Clozapine was called an “atypical” antipsychotic drug because of this dissociation; it produces fewer EPS at equivalent antipsychotic doses in humans and laboratory animals. As a result, there has been a major shift in clinical practice away from typical or first-generation antipsychotic drugs toward the use of an ever-increasing number of atypical or second-generation drugs, which have other advantages as well. The introduction of antipsychotic drugs led to massive changes ...

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