Many of the newer atypical antipsychotics have been associated with weight gain and in some instances diabetes,61 the prevalence of which is twofold greater among schizophrenics than in the general population.62 These are serious side effects for drugs that are used chronically. However, metabolic syndrome, including abdominal obesity, dyslipidemia, hypertension, and insulin resistance, have an increased prevalence in schizophrenics63 which may be genetically related. Weight gain in schizophrenics has been associated with the histamine H1 receptor affinity of antipyschotic medications86 with clozapine and olanazepine being the most potent of the current medications (Ki~1nM) and haloperidol (Ki = 1800 nM, the least). The CATIE study55 noted that olanzapine, of the four atypical antipsychotics studied, was associated with the greatest incidence of weight gain (0.9 kg month_ 1) with greater increases in glycosylated hemoglobin, total cholesterol, and triglycerides, effects consistent with the development of metabolic syndrome.
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