Association between antipsychotic treatment and hyperlipidemia among California Medicaid patients with schizophrenia

To examine the risk of hyperlipidemia among people with schizophrenia exposed to new antipsychotics (clozapine, olanzapine, quetiapine, risperidone) compared with those exposed to older generation antipsychotics.

A case-control study of Medi-Cal claims. Cases developed hyperlipidemia after being diagnosed with schizophrenia (ICD-9: 295) and were exposed to only one antipsychotic drug at some point within 12 weeks prior to the hyperlipidemia diagnosis. Hyperlipidemia was defined by diagnostic claim (ICD-9: 272.1-272.4) or prescription claim for antilipemic agents. Cases were matched on gender and age +/- 3 years to patients with schizophrenia who did not develop hyperlipidemia. Conditional logistic regression assessed the risk of antipsychotic exposure, controlling for age, ethnicity, prior type 2 diabetes or hypothyroidism, and exposure to other medications that may cause hyperlipidemia. Analyses were repeated using a 24- and 52-week retrospective exposure windows.

For the 12-week exposure window, olanzapine (OR = 1.20, 95% CI 1.08-1.33) was associated with increased risk of developing hyperlipidemia compared with older antipsychotic medications. Exposure to clozapine (OR = 1.16, 95% CI 0.99-1.37), risperidone (OR = 1.00, 95% CI 0.90-1.12), and quetiapine (OR = 1.01, 95% CI 0.78-1.32) was not. Hypothesis tests comparing the 4 atypicals to one another revealed that the odds ratio for olanzapine was greater than that for risperidone (P = 0.002). Other than clozapine's odds ratio being significant at 24 weeks (OR = 1.22, 95% CI 1.03-1.45), increasing the exposure window to 24 or 52 weeks did not substantially alter the results.

Compared with older generation antipsychotics, exposure to olanzapine and, somewhat less consistently, to clozapine is associated with an increased risk of hyperlipidemia among people with schizophrenia.