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.

研究目的：探讨吸烟与大量咖啡摄入对精神分裂症患者奥氮平（olanzapine）治疗的有效性与安全性的影响，并分析其与基因多态性的关联。
研究方法：本研究纳入120例精神分裂症患者，为其施以为期30天的奥氮平治疗。治疗有效性通过3种不同的精神科评定量表进行评估，安全性则通过评估代谢不良反应与锥体外系症状加以判定。基因分型检测涵盖<i>CYP1A2*1C</i>、<i>CYP1A2*1F</i>及<i>CYP1A1/1A2</i>基因间多态性，同时包含<i>CYP2D6*3</i>、<i>CYP2D6*4</i>与<i>CYP2D6*6</i>位点。
研究结果：吸烟与大量咖啡摄入可降低奥氮平治疗的有效性，并提升其用药安全性（与<i>CYP1A2*1F</i>等位基因相关，协变量分析显示该效应独立于<i>CYP1A2</i>基因型）。奥氮平给药剂量与药物有效性（p ≤ 0.002）及低密度脂蛋白（LDL）水平（p = 0.004）呈负相关。女性与老年患者对治疗的应答更佳（
研究结论：本研究证实吸烟与大量咖啡摄入对奥氮平治疗的有效性与安全性存在影响。<i>CYP1A2</i>基因型与上述效应的相关性仍需进一步研究。奥氮平治疗结局同时受给药剂量、性别、年龄及<i>CYP2D6</i>代谢型状态的影响。