CLINICAL HANDBOOK OF SCHIZOPHRENIA

172 III. SOMATIC TREATMENTantipsychotics have reported prevalence rates of approximately 45% for oligomenorrhea/amenorrhea and 19% for galactorrhea. Furthermore, high prolactin levels inhibit thehypothalamic–pituitary–gonadal axis, resulting not only in high circulating prolactin levelsbut also reduced gonadal hormone levels. Long-term consequences of antipsychoticrelatedhypogonadism include premature bone loss and osteoporosis. Clozapine andquetiapine do not produce sustained elevations of plasma prolactin across their dosagerange. Olanzapine has been shown to produce little effect on prolactin levels, althoughhyperprolactinemia can occur at higher doses. Ziprasidone and aripiprazole, based onlimited data, appear to be prolactin-sparing agents. The development of symptomatichyperprolactinemia during antipsychotic therapy should prompt clinicians to switch to amore prolactin-sparing agent.METABOLIC SIDE EFFECTSThe association between metabolic side effects and antipsychotics, especially atypicalantipsychotics, is well publicized. Hypertension, hyperlipidemia, obesity, and hyperglycemia,when examined individually or together (as part of the metabolic syndrome), representa tremendous source of cardiovascular risk. Patients with schizophrenia have highrates of these metabolic disorders. For example, analysis of baseline data from the CATIEschizophrenia study revealed that approximately 40% of patients met criteria for metabolicsyndrome.Weight GainThe prevalence of obesity in the U.S. general population has been estimated to be 20–30%. In contrast, the prevalence of obesity in the U.S. schizophrenia population (medicated)has been estimated to be between 40 and 60%. Although patients with schizophreniamay be overweight for a variety of reasons, both conventional and atypicalantipsychotics have been shown to cause weight gain in some patients. This is far morethan a cosmetic issue. A link between antipsychotic nonadherence and antipsychoticinducedweight gain has been demonstrated. In addition, obese patients have an increasedrisk of heart disease, hypertension, and diabetes. An increased risk of these medical disordersis important to consider, because a diagnosis of schizophrenia carries with it a relativerisk of mortality that is 1.6–2.6 times greater than that of the general population.Furthermore, the life expectancy of an individual with schizophrenia is 20% less thanthat of the general population. Cardiovascular disease is the number one cause of deathin patients with schizophrenia.Important differences exist among the antipsychotics in terms of weight gain potential.Low-potency conventional antipsychotics have been implicated in weight gain foryears. Data from randomized, controlled trials of atypical antipsychotics in adults demonstratethat weight gain cannot be considered a class effect. Clozapine and olanzapineare associated with the greatest likelihood of clinically significant weight gain. In a metaanalysisthat examined mean weight change at 10 weeks at standard dosages ofantipsychotic medications, clozapine and olanzapine were associated with the greatestweight gain (4.0–4.5 kg). Studies have reported that risperidone and quetiapine are associatedwith moderate weight gain. Ziprasidone and aripiprazole are associated with theleast likelihood of weight gain and have been described as weight neutral. Althoughziprasidone and aripiprazole are associated with substantially less weight gain potential,significant weight gain (i.e., at least 7% of initial body weight) was experienced by 9%