CLINICAL HANDBOOK OF SCHIZOPHRENIA

17. Side Effects of Antipsychotics 175a variety of antipsychotics, an oral glucose tolerance test revealed that fasting glucose andinsulin levels were higher with olanzapine, risperidone, and clozapine compared to levelsin psychiatric patients taking typical antipsychotics and normal volunteers. These resultssuggest a link between insulin resistance and several atypical antipsychotics. The incidenceof newly diagnosed diabetes was retrospectively assessed over a 2-year period inmore than 56,000 veterans with schizophrenia who were consistently prescribed clozapine,risperidone, olanzapine, quetiapine, or a conventional antipsychotic. Overall, 4.4%of patients were diagnosed with diabetes annually, and the attributable risk of developingdiabetes was low but varied among medications: clozapine, 2.0%; quetiapine, 0.8%;olanzapine, 0.6%; and risperidone, 0.1% (Leslie & Rosenheck, 2004).Although the risk of developing diabetes or exacerbating existing diabetes cases as aresult of atypical antipsychotic therapy appears small, the seriousness of diabetes necessitatesthat clinicians obtain baseline parameters (height, weight, waist circumference, bodymass index, and fasting blood sugar; see Table 17.2), then monitor such parametersthroughout treatment (American Diabetes Association, 2004). Patients should be encouragedto monitor their own weight as well. Clinicians should consider switching patientswhose glycemic control worsens to an antipsychotic with a low propensity to cause orworsen diabetes. The development of severe hyperglycemia, with or without symptoms,should prompt immediate medical care.CARDIAC SIDE EFFECTSThere has been a concern that atypical antipsychotics may slow cardiac conduction, producingQT interval prolongation and predisposing patients to arrhythmias. In general,atypical antipsychotics have only modest and usually clinically unimportant effects on theQT interval. Among the atypical antipsychotics, ziprasidone has the greatest potential toprolong a patient’s QT interval, although published data generally do not report significantelectrocardiographic (ECG) abnormalities. In patients with preexisting QT prolongation,the use of ziprasidone may not be warranted. In general, patients older than age 45 and individualswith preexisting cardiac conduction abnormalities should have a baseline EKG performedprior to initiating any antipsychotic therapy and periodically thereafter (see Table 17.2).Of all the atypical antipsychotics, clozapine has been singled out because of its potentialcardiac toxicity. Recently, investigators reviewed the published literature to examinethe risk of myocarditis, pericarditis, and cardiomyopathy in patients treated withclozapine. The authors found 65 cases of myocarditis, 6 cases of pericarditis, and 52cases of cardiomyopathy in patients treated with clozapine. Although the incidence rateof clozapine-associated cardiac side effects is undetermined, there clearly is a relationshipbetween clozapine and myocarditis and cardiomyopathy. It is important to note thatthese side effects are uncommon yet serious. Some authors have suggested that patientsprescribed clozapine should be assessed for myocarditis in the first month of treatmentand assessed regularly for cardiomyopathy. Most importantly, health care professionalsshould remain vigilant if any cardiac symptoms develop in patients prescribed clozapine.Orthostatic HypotensionOrthostasis has been reported to occur most commonly with the use of low-potency conventionalantipsychotics, especially chlorpromazine and thioridazine. Postural hypotensionis also relatively common with the atypical antipsychotic clozapine. Other atypicalantipsychotics also occasionally lead to orthostasis, especially risperidone and quetiapine.The potential for quetiapine to cause orthostasis, particularly in older adults, is one of the