Low baseline serotonin-2A receptors predict clinical response to olanzapine in first-episode schizophrenia patients

The purpose of this study was to determine whether platelet serotonin-2A (5-HT2A) binding sites and inositol 1,4,5 trisphosphate (IP3) concentrations before treatment can identify olanzapine-responsive patients. The study included 21 never medicated, first-episode schizophrenia patients (antipsychotic-naïve) and 21 patients with a DSM-IV-TR diagnosis of paranoid schizophrenia who had not received depot antipsychotic treatment in the previous 6 months or oral antipsychotic or antidepressant treatment in the previous 2 months (antipsychotic-free). In the antipsychotic-naïve group, olanzapine responders had a significantly lower number of 5-HT2A receptors and lower IP3 concentrations at baseline than non-responders. The combination of baseline 5-HT2A and IP3 values significantly predicted an improvement in negative symptomatology after 6 weeks of treatment with olanzapine. In the antipsychotic-free group, responders had significantly higher positive and lower negative symptomatology at baseline, together with a reduced number of 5-HT2A receptors. However, basal 5-HT2A receptors or IP3 concentrations did not significantly predict positive, negative or general clinical response. The reported results suggest that platelet 5-HT2A binding might be a trait marker that could help to identify those patients likely to show greater improvement in negative symptomatology after olanzapine treatment.