Influence of serotonergic transmission on response to olanzapine

Introduction. This study aimed to investigate associations between the response to olanzapine and genetic variations (polymorpbisms) in serotonergic transmission related genes in a sample of prospectively studied schizophrenic patients treated with this drug. Methodology. A total of 51 non-related patients with a DSM-IV diagnosis of schizophrenia were treated with olanzapine (mean dose: 12 mg/day; range: 5-25 mg) and followed-up for at least three months. Response to olanzapine was measured by the difference between baseline and post-treatment scores on the PANSS and GAS scales, The following polymorphisms were studied: serotonin receptor 5-HT2A (102-T/C, His452Tyr), serotonin receptor 5-HT2C (Cys23Ser, -330-GGT/-244-CT), and serotonin transporter (VNTR, 5-HTTLPR). Results. Global clinical improvement, measured with both the GAS and PANSS total scores, was observed. When patients were divided into responders and non-responders, the distribution of genotypic and allelic frequencies was similar to the one observed in previous studies with clozapine. When regression analyses were undertaken, polymorpbism -330-GT/-244-CT of the 5-HT2C serotonin receptor and 5-HTTLPR of the serotonin transporter showed a tendency towards the association to olanzapine response. Conclusions. The present study provides preliminary evidence of the important role of variations in serotonin transmission related genes in determining clinical response to olanzapine. Considering previous studies, it can also be concluded that olanzapine and clozapine may have similar affinities to serotonin receptors.