According to the American Psychiatric Association, second-generation (atypical) antipsychotics (SGAs)—with the exception of clozapine—are the agents of choice for first-line treatment of schizophrenia.16,25 Clozapine is not recommended because of its risk of agranulocytosis.2 SGAs are usually preferred over first-generation (typical) antipsychotics (FGAs) because they are associated with fewer extrapyramidal symptoms.2 However, SGAs tend to have metabolic side effects, such as weight gain, hyperlipidemia, and diabetes mellitus.26 These adverse effects can contribute to the increased risk of cardiovascular mortality observed in schizophrenia patients.26

The Texas Medication Algorithm Project (TMAP) has provided a six-stage pharmacotherapeutic algorithm for the treatment of schizophrenia. Stage 1 is first-line monotherapy with an SGA. If the patient shows little or no response, he or she should proceed to stage 2, which consists of monotherapy with either another SGA or an FGA. If there is still no response, the patient should move to stage 3, which consists of clozapine monotherapy with monitoring of the white blood cell (WBC) count.24 If agranulocytosis occurs, clozapine should be discontinued. If stage-3 therapy fails to elicit a response, the patient should proceed to stage 4, which combines clozapine with an FGA, an SGA, or electroconvulsive therapy (ECT).24 If the patient still shows no response to treatment, stage 5 calls for monotherapy with an FGA or an SGA that has not been tried.24 Finally, if stage 5 treatment is unsuccessful, stage 6 consists of combination therapy with an SGA, an FGA, ECT, and/or a mood stabilizer.