Natasa Djordjevic1, Branimir Radmanovic2,3, Jelena Cukic4, Dejan Baskic5, Slavica Djukic-Dejanovic3, Dragan Milovanovic1, Eleni Aklillu6. 1. Department of Pharmacology and toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia. 2. Department of Psychiatry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia. 3. Psychiatry Clinic, Clinical Centre "Kragujevac", Kragujevac, Serbia. 4. Public Health Institute, Kragujevac, Serbia. 5. Department of Microbiology and immunology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia. 6. Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Abstract
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 CYP1A2*1C, CYP1A2*1F and CYP1A1/1A2 intergenic polymorphism, as well as CYP2D6*3, CYP2D6*4 and CYP2D6*6. Results: Cigarette smoking and heavy coffee consumption decreased the efficacy and increased the safety of olanzapine treatment (P < 0.001). Although the effect was detected only in carriers of CYP1A2*1F allele, covariate analysis revealed that it is independent of CYP1A2 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 < 0.026), but had more certain adverse effects (P ≤ 0.049). When controlling for other relevant factors, CYP2D6 metabolizer status affects olanzapine efficacy (P = 0.032).Conclusions: We confirm the effect of cigarette smoking and heavy coffee consumption on olanzapine efficacy and safety. The relevance of CYP1A2 genotype for the described effect needs further investigation. Olanzapine treatment outcome is also affected by dose, sex, age and CYP2D6 metabolizer status.
Objectives: To evaluate the effect of cigarette smoking and heavy coffee consumption on efficacy and safety of olanzapine treatment in schizophreniapatients, 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 CYP1A2*1C, CYP1A2*1F and CYP1A1/1A2 intergenic polymorphism, as well as CYP2D6*3, CYP2D6*4 and CYP2D6*6. Results: Cigarette smoking and heavy coffee consumption decreased the efficacy and increased the safety of olanzapine treatment (P < 0.001). Although the effect was detected only in carriers of CYP1A2*1F allele, covariate analysis revealed that it is independent of CYP1A2 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 < 0.026), but had more certain adverse effects (P ≤ 0.049). When controlling for other relevant factors, CYP2D6 metabolizer status affects olanzapine efficacy (P = 0.032).Conclusions: We confirm the effect of cigarette smoking and heavy coffee consumption on olanzapine efficacy and safety. The relevance of CYP1A2 genotype for the described effect needs further investigation. Olanzapine treatment outcome is also affected by dose, sex, age and CYP2D6 metabolizer status.
Authors: Syeda Tayyaba Rehan; Abdul Hannan Siddiqui; Zayeema Khan; Laiba Imran; Abdul Ahad Syed; Muhammad Junaid Tahir; Zahra Jassani; Manjeet Singh; Muhammad Sohaib Asghar; Ali Ahmed Journal: Ann Med Surg (Lond) Date: 2022-06-30