Impact of CYP2C19 genotype on sertraline exposure in 1200 Scandinavian patients.
Journal
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
ISSN: 1740-634X
Titre abrégé: Neuropsychopharmacology
Pays: England
ID NLM: 8904907
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
14
06
2019
accepted:
19
10
2019
revised:
24
09
2019
pubmed:
28
10
2019
medline:
29
12
2020
entrez:
26
10
2019
Statut:
ppublish
Résumé
Sertraline is an (SSRI-)antidepressant metabolized by the polymorphic CYP2C19 enzyme. The aim of this study was to investigate the impact of CYP2C19 genotype on the serum concentrations of sertraline in a large patient population. Second, the proportions of patients in the various CYP2C19 genotype-defined subgroups obtaining serum concentrations outside the therapeutic range of sertraline were assessed. A total of 2190 sertraline serum concentration measurements from 1202 patients were included retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into CYP2C19 genotype-predicted phenotype subgroups, i.e. normal (NMs), ultra rapid (UMs), intermediate (IMs), and poor metabolisers (PMs). The differences in dose-harmonized serum concentrations of sertraline and N-desmethylsertraline-to-sertraline metabolic ratio were compared between the subgroups, with CYP2C19 NMs set as reference. The patient proportions outside the therapeutic concentration range were also compared between the subgroups with NMs defined as reference. Compared with the CYP2C19 NMs, the sertraline serum concentration was increased 1.38-fold (95% CI 1.26-1.50) and 2.68-fold (95% CI 2.16-3.31) in CYP2C19 IMs and PMs, respectively (p < 0.001), while only a marginally lower serum concentration (-10%) was observed in CYP2C19 UMs (p = 0.012). The odds ratio for having a sertraline concentration above the therapeutic reference range was 1.97 (95% CI 1.21-3.21, p = 0.064) and 8.69 (95% CI 3.88-19.19, p < 0.001) higher for IMs and PMs vs. NMs, respectively. CYP2C19 IMs and PMs obtain significantly higher serum concentrations of sertraline than NMs. Based on the relative differences in serum concentrations compared to NMs, dose reductions of 60% and 25% should be considered in PMs and IMs, respectively, to reduce the risk of sertraline overexposure in these patients.
Identifiants
pubmed: 31649299
doi: 10.1038/s41386-019-0554-x
pii: 10.1038/s41386-019-0554-x
pmc: PMC6969041
doi:
Substances chimiques
Antidepressive Agents
0
Serotonin Uptake Inhibitors
0
CYP2C19 protein, human
EC 1.14.14.1
Cytochrome P-450 CYP2C19
EC 1.14.14.1
Sertraline
QUC7NX6WMB
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
570-576Références
Grimsley SR, Jann MW. Paroxetine, sertraline, and fluvoxamine: new selective serotonin reuptake inhibitors. Clin Pharm. 1992;11:930–57.
pubmed: 1464219
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet. 2018;391:1357–66.
doi: 10.1016/S0140-6736(17)32802-7
Lundmark J, Reis M, Bengtsson F. Therapeutic drug monitoring of sertraline: variability factors as displayed in a clinical setting. Ther Drug Monit. 2000;22:446–54.
doi: 10.1097/00007691-200008000-00014
Hedayati SS, Gregg LP, Carmody T, Jain N, Toups M, Rush AJ. et al. Effect of sertraline on depressive symptoms in patients with chronic kidney disease without dialysis dependence: the CAST randomized clinical trial. JAMA. 2017;318:1876–90.
doi: 10.1001/jama.2017.17131
Lydiard RB, Stahl SM, Hertzman M, Harrison WM. A double-blind, placebo-controlled study comparing the effects of sertraline versus amitriptyline in the treatment of major depression. J Clin Psychiatry. 1997;58:484–91.
doi: 10.4088/JCP.v58n1104
Reis M, Aberg-Wistedt A, Agren H, Hoglund P, Akerblad AC, Bengtsson F. Serum disposition of sertraline, N-desmethylsertraline and paroxetine: a pharmacokinetic evaluation of repeated drug concentration measurements during 6 months of treatment for major depression. Hum Psychopharmacol. 2004;19:283–91.
doi: 10.1002/hup.599
Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, et al. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000;157:1445–52.
doi: 10.1176/appi.ajp.157.9.1445
Obach RS, Cox LM, Tremaine LM. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos. 2005;33:262–70.
doi: 10.1124/dmd.104.002428
Saiz-Rodriguez M, Belmonte C, Roman M, Ochoa D, Koller D, Talegon M, et al. Effect of polymorphisms on the pharmacokinetics, pharmacodynamics and safety of sertraline in healthy volunteers. Basic Clin Pharm Toxicol. 2018;122:501–11.
doi: 10.1111/bcpt.12938
Sim SC, Risinger C, Dahl ML, Aklillu E, Christensen M, Bertilsson L, et al. A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharm Ther. 2006;79:103–13.
doi: 10.1016/j.clpt.2005.10.002
Hicks JK, Bishop JR, Sangkuhl K, Muller DJ, Ji Y, Leckband SG, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors. Clin Pharm Ther. 2015;98:127–34.
doi: 10.1002/cpt.147
Zhou Y, Ingelman-Sundberg M, Lauschke VM. Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin Pharm Ther. 2017;102:688–700.
doi: 10.1002/cpt.690
Wang JH, Liu ZQ, Wang W, Chen XP, Shu Y, He N, et al. Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharm Ther. 2001;70:42–7.
doi: 10.1067/mcp.2001.116513
Rudberg I, Hermann M, Refsum H, Molden E. Serum concentrations of sertraline and N-desmethyl sertraline in relation to CYP2C19 genotype in psychiatric patients. Eur J Clin Pharmacol. 2008;64:1181–8.
doi: 10.1007/s00228-008-0533-3
Hiemke C, Bergemann N, Clement HW, Conca A, Deckert J, Domschke K, et al. Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry 2018;51:9–62.
doi: 10.1055/s-0043-116492
Meyer JH, Wilson AA, Sagrati S, Hussey D, Carella A, Potter WZ, et al. Serotonin transporter occupancy of five selective serotonin reuptake inhibitors at different doses: an [11C]DASB positron emission tomography study. Am J Psychiatry. 2004;161:826–35.
doi: 10.1176/appi.ajp.161.5.826
Furukawa TA, Cipriani A, Cowen PJ, Leucht S, Egger M, Salanti G. Optimal dose of selective serotonin reuptake inhibitors, venlafaxine, and mirtazapine in major depression: a systematic review and dose-response meta-analysis. Lancet Psychiatry. 2019;6:601–9.
doi: 10.1016/S2215-0366(19)30217-2
Hieronymus F, Nilsson S, Eriksson E. A mega-analysis of fixed-dose trials reveals dose-dependency and a rapid onset of action for the antidepressant effect of three selective serotonin reuptake inhibitors. Transl Psychiatry. 2016;6:e834.
doi: 10.1038/tp.2016.104
Jakubovski E, Varigonda AL, Freemantle N, Taylor MJ, Bloch MH. Systematic review and meta-analysis: dose-response relationship of selective serotonin reuptake inhibitors in major depressive disorder. Am J Psychiatry. 2016;173:174–83.
doi: 10.1176/appi.ajp.2015.15030331
Jukic MM, Haslemo T, Molden E, Ingelman-Sundberg M. Impact of CYP2C19 genotype on escitalopram exposure and therapeutic failure: a retrospective study based on 2,087 patients. Am J Psychiatry. 2018;175:463–70.
doi: 10.1176/appi.ajp.2017.17050550
Kobayashi K, Ishizuka T, Shimada N, Yoshimura Y, Kamijima K, Chiba K. Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P-450 in vitro. Drug Metab Dispos. 1999;27:763–6.
pubmed: 10383917
Lee DO, Lee CD. Serotonin syndrome in a child associated with erythromycin and sertraline. Pharmacotherapy 1999;19:894–6.
doi: 10.1592/phco.19.10.894.31561
Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BC. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clin Ther 1999;21:1890–9.
doi: 10.1016/S0149-2918(00)86737-5