Objective: To compare (1) mean low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride differences after switching from olanzapine to quetiapine, risperidone, or ziprasidone and (2) the mean lipid change between switch patterns.

Design: Retrospective, naturalistic, nonequivalent control group design.

Setting: United States between April 1, 2002, and September 30, 2002.

Patients: 1,826 U.S. Veterans Healthcare System enrollees with diagnoses of schizophrenia or schizoaffective disorders and receiving a second-generation antipsychotic (SGA) medication.

Interventions: Analysis of data from the Veterans Information Systems and Technology Architecture.

Main Outcome Measures: Differences in LDL-C, HDL-C, and triglycerides and mean differences between switch patterns. Predictors were the type of switch (e.g., olanzapine to quetiapine) and switch patterns (e.g., olanzapine to quetiapine versus olanzapine to risperidone). Data were analyzed using Pearson's X2 and multivariate analysis of covariance with planned comparisons.

Results: After adjusting for age, gender, and race/ethnicity, LDL-C decreased significantly among patients switched from olanzapine to ziprasidone (-16.9 mg/dL, P <0.01) and olanzapine to quetiapine (-7.6 mg/dL, P = 0.04) and trended upward in patients switched from olanzapine to risperidone (+6.6 mg/dL, P = 0.12). Triglyceride levels decreased among those switched from olanzapine to ziprasidone (-62.9 mg/dL, P <0.01) and olanzapine to risperidone (-48.5 mg/dL, P <0.01) but not among veterans switched from olanzapine to quetiapine (+7.8 mg/dL, P = 0.54). HDL-C levels did not change significantly when veterans were switched from olanzapine to quetiapine, risperidone, or ziprasidone.

Conclusion: Switching SGAs can increase or decrease cardiovascular risk depending on the clinician's follow-on SGA choice. LDL-C and triglyceride levels decreased significantly among veterans switched from olanzapine to ziprasidone. Switching to quetiapine was associated with a reduction in LDL-C, while switching to risperidone resulted in lower triglyceride levels. Clinicians should use these results when building a patient care plan that includes switching of SGAs.

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