M S Zastrozhin1, VYu Skryabin1, F Rwere1, A E Petukhov1, E P Pankratenko1, S A Pozdniakov1, V A Ivanchenko1, V V Noskov1, I A Zaytsev1, N V Vinokurova1, D S Horyaev1, R V Vlasovskih1, E A Bryun1, D A Sychev1. 1. Zastrozhin, PhD, M.D., Postdoctoral Fellow, 1University of California, San Francisco, CA, USA; Head of laboratory of genetics and fundamental studies, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; Associate professor of addiction psychiatry department,Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. Skryabin, PhD, M.D., head of clinical department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; Associate professor of addiction psychiatry department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. Rwere, PhD, instructor of the department of Anesthesiology, perioperative and pain medicine, Stanford University School of Medicine, Stanford, CA, USA. Petukhov, PhD, M.D., clinical laboratory diagnostician of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; associate professor of pharmaceutical and toxicological chemistry, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation. Pankratenko, paramedic-laboratory assistant of the analytical toxicology lab of the Reference center for psychoactive substances use monitoring, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Pozdniakov, researcher of the laboratory of genetics and fundamental studies, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Ivanchenko, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Noskov, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Zaytsev, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Vinokurova, laboratory assistant, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Horyaev, M.D., psychiatrist, addiction psychiatrist of clinical department, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Vlasovskih, PhD, M.D., vice-director, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia. Bryun, PhD, M.D., professor, president, Moscow Research and Practical Centre on Addictions of the Moscow Department of Healthcare, Moscow, Russia; head of addiction psychiatry department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation. Sychev, corresponding member of the Academy of Sciences of Russia, M.D., PhD, professor, rector, head of clinical pharmacology and therapy department, Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation, Moscow, Russian Federation.
Abstract
Introduction: Escitalopram is commonly prescribed to patients with recurrent depressive disorder. Some of them do not show adequate response to treatment with escitalopram, while many of them experience adverse drug reactions. Objective: The objective of our study was to evaluate the impact of -806C>T polymorphism of CYP2C19 (CYP2C19*17) on the concentration/dose ratio of escitalopram in patients with recurrent depressive disorder. Material and methods: Our study enrolled 267 patients with recurrent depressive disorder (average age -40.2 ± 16.4 years). Treatment regimen included escitalopram in an average daily dose of 12.5 ± 5.0 mg per day. The efficacy and safety rates of treatment were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results: Our findings revealed the statistically significant results in terms of both treatment efficacy evaluation (HAMD scores at the end of the treatment course): (CC) 9.0 [7.0; 11.0], (CT) 4.0 [2.0; 6.0] and (TT) 2.0 [1.0; 4.0], p < 0.001; and safety profile (the UKU scores): (CC) 7.0 [7.0; 8.0], (CT) 3.0 [3.0; 4.0] and (TT) 3.0 [2.0; 3.0], p < 0.001. We revealed no statistically significant results for the concentration/dose ratio of escitalopram in patients with different genotypes: (CC) 5.762 [3.939; 9.076], (CT) 5.714 [3.485; 8.533] and (TT) 7.388 [4.618; 10.167], p = 0.268). Conclusion: The CYP2C19*17 genetic variant significantly affected the efficacy and safety profiles of escitalopram in a group of 267 patients with recurrent depressive disorder but did not greatly affect its equilibrium plasma concentration.
Introduction: Escitalopram is commonly prescribed to patients with recurrent depressive disorder. Some of them do not show adequate response to treatment with escitalopram, while many of them experience adverse drug reactions. Objective: The objective of our study was to evaluate the impact of -806C>T polymorphism of CYP2C19 (CYP2C19*17) on the concentration/dose ratio of escitalopram in patients with recurrent depressive disorder. Material and methods: Our study enrolled 267 patients with recurrent depressive disorder (average age -40.2 ± 16.4 years). Treatment regimen included escitalopram in an average daily dose of 12.5 ± 5.0 mg per day. The efficacy and safety rates of treatment were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Therapeutic drug monitoring has been performed using HPLC-MS/MS. Results: Our findings revealed the statistically significant results in terms of both treatment efficacy evaluation (HAMD scores at the end of the treatment course): (CC) 9.0 [7.0; 11.0], (CT) 4.0 [2.0; 6.0] and (TT) 2.0 [1.0; 4.0], p < 0.001; and safety profile (the UKU scores): (CC) 7.0 [7.0; 8.0], (CT) 3.0 [3.0; 4.0] and (TT) 3.0 [2.0; 3.0], p < 0.001. We revealed no statistically significant results for the concentration/dose ratio of escitalopram in patients with different genotypes: (CC) 5.762 [3.939; 9.076], (CT) 5.714 [3.485; 8.533] and (TT) 7.388 [4.618; 10.167], p = 0.268). Conclusion: The CYP2C19*17 genetic variant significantly affected the efficacy and safety profiles of escitalopram in a group of 267 patients with recurrent depressive disorder but did not greatly affect its equilibrium plasma concentration.
Authors: Sarah C Sim; Carl Risinger; Marja-Liisa Dahl; Eleni Aklillu; Magnus Christensen; Leif Bertilsson; Magnus Ingelman-Sundberg Journal: Clin Pharmacol Ther Date: 2006-01 Impact factor: 6.875
Authors: J K Hicks; J R Bishop; K Sangkuhl; D J Müller; Y Ji; S G Leckband; J S Leeder; R L Graham; D L Chiulli; A LLerena; T C Skaar; S A Scott; J C Stingl; T E Klein; K E Caudle; A Gaedigk Journal: Clin Pharmacol Ther Date: 2015-06-29 Impact factor: 6.875