Pharmacopsychiatry 2014; 47(06): 210-214
DOI: 10.1055/s-0034-1383655
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Therapeutic Drug Monitoring of Mirtazapine in a Routine Outpatient Setting in Asian Psychiatric Patients

W. Myung*
1   Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
,
J.-H. Jang*
2   Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
,
H. Yoon
1   Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
,
S.-Y. Lee#
2   Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
,
D. K. Kim#
1   Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
› Author Affiliations
Further Information

Publication History

received 13 March 2014
revised 30 May 2014

accepted 11 June 2014

Publication Date:
31 July 2014 (online)

Abstract

Introduction:  Mirtazapine is an antidepressant that acts by enhancing serotonergic and noradrenergic neurotransmission. This study aimed to evaluate mirtazapine pharmacokinetic data from Korean psychiatric patients and to identify the potential factors affecting its steady-state concentration.

Methods:  A total of 337 samples of steady-state mirtazapine concentrations from 188 adult psychiatric outpatients were retrospectively evaluated. Serum mirtazapine concentrations were measured by high-performance liquid chromatography-tandem mass spectrometry.

Results:  Median mirtazapine concentration was 43.6 μg/L (164.37 nmol) at a daily dosage range of 7.5–60 mg. At the steady state, mirtazapine dose had a positive correlation with the drug concentration. Mean concentration-to-dose (C/D) ratio was 1.48 μg/L/mg/day (5.58 nmol/mg/day), which was higher than that in a previous study in Caucasian subjects. Age and paroxetine co-medication were positively associated with C/D ratio. Initial mirtazapine concentration and C/D ratio did not show an association with responsiveness in depressive patients.

Discussion:  This study presented the therapeutic drug monitoring data for mirtazapine and pharmacokinetic variations of mirtazapine in an Asian population. A further study could be helpful for clinical decision making based on the characteristics of patients.

* These individuals contributed equally to this article as co-first authors.


# These individuals contributed equally to this article as co-corresponding authors.


 
  • References

  • 1 De Boer T, Nefkens F, Van Helvoirt A. The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo. Eur J Pharmacol 1994; 253: R5-R6
  • 2 Watanabe N, Omori IM, Nakagawa A et al. Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and meta-analysis. J Clin Psychiatry 2008; 69: 1404-1415
  • 3 Thase ME, Nierenberg AA, Vrijland P et al. Remission with mirtazapine and selective serotonin reuptake inhibitors: a meta-analysis of individual patient data from 15 controlled trials of acute phase treatment of major depression. Int Clin Psychopharmacol 2010; 25: 189-198
  • 4 Watanabe N, Omori IM, Nakagawa A et al. Mirtazapine versus other antidepressive agents for depression. Cochrane Database Syst Rev 2011; CD006528
  • 5 Timmer CJ, Lohmann AAM, Mink CPA. Pharmacokinetic dose-proportionality study at steady state of mirtazapine from Remeron® tablets. Hum Psychopharmacol 1995; 10: S97-S106
  • 6 Timmer CJ, Paanakker JE, Van Hal HJM. Pharmacokinetics of mirtazapine from orally administered tablets: influence of gender, age and treatment regimen. Hum Psychopharmacol 1996; 11: 497-509
  • 7 Dodd S, Boulton DW, Burrows GD et al. In vitro metabolism of mirtazapine enantiomers by human cytochrome P450 enzymes. Hum Psychopharmacol 2001; 16: 541-544
  • 8 Dahl ML, Voortman G, Alm C et al. In vitro and in vivo studies on the disposition of mirtazapine in humans. Clin Drug Invest 1997; 13: 37-46
  • 9 Delbressine LP, Vos RM. The clinical relevance of preclinical data: mirtazapine, a model compound. J Clin Psychopharmacol 1997; 17 (Suppl. 01) 29S-33S
  • 10 Timmer CJ, Sitsen JM, Delbressine LP. Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet 2000; 38: 461-474
  • 11 Reis M, Prochazka J, Sitsen A et al. Inter- and intraindividual pharmacokinetic variations of mirtazapine and its N-demethyl metabolite in patients treated for major depressive disorder: a 6-month therapeutic drug monitoring study. Ther Drug Monit 2005; 27: 469-477
  • 12 Shams M, Hiemke C, Hartter S. Therapeutic drug monitoring of the antidepressant mirtazapine and its N-demethylated metabolite in human serum. Ther Drug Monit 2004; 26: 78-84
  • 13 Meineke I, Kress I, Poser W et al. Therapeutic drug monitoring of mirtazapine and its metabolite desmethylmirtazapine by HPLC with fluorescence detection. Ther Drug Monit 2004; 26: 277-283
  • 14 Lind A-B, Reis M, Bengtsson F et al. Steady-state concentrations of mirtazapine, N-desmethylmirtazapine, 8-hydroxymirtazapine and their enantiomers in relation to cytochrome P450 2D6 genotype, age and smoking behaviour. Clinical pharmacokinetics 2009; 48: 63-70
  • 15 Hong Ng NC, Norman TR, Naing KO et al. A comparative study of sertraline dosages, plasma concentrations, efficacy and adverse reactions in Chinese versus Caucasian patients. Int Clin Psychopharmacol 2006; 21: 87-92
  • 16 Kim K, Johnson JA, Derendorf H. Differences in drug pharmacokinetics between East Asians and Caucasians and the role of genetic polymorphisms. J Clin Pharmacol 2004; 44: 1083-1105
  • 17 Fabrega HJ. Cultural challenges to the psychiatric enterprise. Compr Psychiatry 1995; 36: 377-383
  • 18 Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance. Clin Pharmacokinet 2009; 48: 761-804
  • 19 Yoo HD, Lee SN, Kang HA et al. Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with CYP2D6*10/*10. Br J Pharmacol 2011; 164: 433-443
  • 20 Johansson I, Oscarson M, Yue QY et al. Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol 1994; 46: 452-459
  • 21 Grasmader K, Verwohlt PL, Kuhn KU et al. Population pharmacokinetic analysis of mirtazapine. Eur J Clin Pharmacol 2004; 60: 473-480
  • 22 Hiemke C, Baumann P, Bergemann N et al. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011. Pharmacopsychiatry 2011; 44: 195-235
  • 23 Ruwe FJ, Smulders RA, Kleijn HJ et al. Mirtazapine and paroxetine: a drug-drug interaction study in healthy subjects. Hum Psychopharmacol 2001; 16: 449-459
  • 24 Sproule BA, Naranjo CA, Brenmer KE et al. Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence. Clin Pharmacokinet 1997; 33: 454-471