Second-generation antipsychotic exposure and metabolic-related disorders in patients with schizophrenia: An observational pharmacoepidemiology study from 1988 to 2002

Patients with schizophrenia are at increased risk for cardiovascular disease as a consequence of lifestyle habits, impaired access to health care, and, increasingly, due to metabolic side effects ostensibly attributed to second-generation antipsychotics (SGAs). There is little evidence, however, on the extent and temporal patterns of SGA-associated metabolic side effects. We longitudinally examined the differential prevalence rates of obesity, diabetes mellitus, and diabetic ketoacidosis among inpatients with schizophrenia compared with control inpatients without schizophrenia. The data were derived from the National Inpatient Sample, the largest all-payer inpatient care database in the United States consisting of 5 to 8 million inpatient hospital stays per year sampled to approximate a 20% sample of community hospitals from 1988 to 2002. Overlaid on these observations was the market penetration data for SGAs. In 1988, the net difference from controls in obesity prevalence among inpatients with schizophrenia was +4.7%; by 2002, this difference had widened to +14.7%. Similarly, a significant increase in net prevalence of diabetes mellitus and diabetic ketoacidosis was observed from 1988 to 2002 among schizophrenic inpatients. In conclusion, after the introduction of SGAs, patients with schizophrenia in the United States have experienced a striking net increase in the prevalence of obesity and diabetes mellitus. This is likely to significantly add to an already elevated risk for cardiovascular disease in this population. Further investigations are urgently required so that health policy can be appropriately amended for preventive measures.