Objective: 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.
Methods: 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.
Results: 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.
Conclusions: 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.