Cigarette smoking and heavy coffee consumption affecting response to olanzapine: the role of genetic polymorphism

Objectives: To evaluate the effect of cigarette smoking and heavy coffee consumption on efficacy and safety of olanzapine treatment in schizophrenia patients, in relation to genetic polymorphism. Methods: The study involved 120 patients with schizophrenia, treated with olanzapine for 30 days. Therapy efficacy was determined using three different psychiatric scales, and safety by assessing metabolic adverse effects and extrapyramidal symptoms. Genotyping included <i>CYP1A2*1C</i>, <i>CYP1A2*1F</i> and <i>CYP1A1/1A2</i> intergenic polymorphism, as well as <i>CYP2D6*3</i>, <i>CYP2D6*4</i> and <i>CYP2D6*6</i>. Results: Cigarette smoking and heavy coffee consumption decreased the efficacy and increased the safety of olanzapine treatment (p CYP1A2*1F allele, covariate analysis revealed that it is independent of <i>CYP1A2</i> genotype. Olanzapine dose was inversely correlated with the drug efficacy (p ≤ 0.002) and LDL level (p = 0.004). Women and older subjects responded better to therapy (p Conclusions: We confirm the effect of cigarette smoking and heavy coffee consumption on olanzapine efficacy and safety. The relevance of <i>CYP1A2</i> genotype for the described effect needs further investigation. Olanzapine treatment outcome is also affected by dose, sex, age and CYP2D6 metabolizer status.