Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness Study

Background: C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment. Methods: The IM outcomes were compared between antipsychotic treatment groups in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial phase 1 with subjects with laboratory assessments at baseline and 3 months (n = 789). Results: There were significant treatment differences in CRP, E-selectin, and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than perphenazine (p =.001) for E-selectin, and in those with low baseline CRP (<1 mg/L), olanzapine was significantly different than perphenazine (p <.001), risperidone (p <.001), and ziprasidone (p =.002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant versus olanzapine (p =.010), quetiapine (p =.010), and risperidone (p =.006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP. Conclusions: This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients.