Pharmacopsychiatry 2015; 48(06): 215-218
DOI: 10.1055/s-0035-1559666
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Retrospective Pilot Study for Analysis of Antidepressant Serum Concentrations of Citalopram and Venlafaxine during Inflammation

G. Hefner
1   Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany
2   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Germany
,
M. E. E. Shams
3   Faculty of Pharmacy, Department of Pharmaceutics, University of Mansoura, Egypt
4   Department of Pharmacy Practice, College of Health Sciences, Ministry of Health, Oman
,
S. Unterecker
5   Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany
,
T. Falter
2   Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Germany
,
C. Hiemke
1   Department of Psychiatry and Psychotherapy, University Medical Centre Mainz, Germany
› Author Affiliations
Further Information

Publication History

received 20 May 2015
revised 17 July 2015

accepted 23 July 2015

Publication Date:
03 September 2015 (online)

Abstract

Introduction: Inflammation-mediated changes in drug metabolism may increase drug levels in blood and lead to intoxications. The objective of this study was to find out whether elevated serum levels of C-reactive protein (CRP) are associated with increased serum concentrations of the antidepressants citalopram and venlafaxine.

Methods: Therapeutic drug monitoring request forms of psychiatric patients were screened retrospectively. The serum concentrations in relation to the daily doses [(C/D) (ng/ml/mg)] and the metabolic ratios (metabolite/drug) were compared intraindividually under normal (<5 mg/l) and pathological (>5 mg/l) condition by the Wilcoxon signed-rank test.

Results: Elevated levels of CRP were not associated with a significant (P>0.05) increase in C/D for citalopram (2.4 ng/ml/mg vs. 2.85 ng/ml/mg, N=15) or in C/D for the active moiety of venlafaxine (1.76 ng/ml/mg vs. 1.68 ng/ml/mg, N=39), compared with normal CRP serum levels. No significant difference in the metabolic ratio was observed in both groups.

Discussion: There was no major effect of inflammation on the metabolism of citalopram and venlafaxine. Because of the broad therapeutic indices of these 2 drugs, the drugs seem to be a good choice for the treatment of depression, even if an infection occurs.

 
  • References

  • 1 Hurlimann J, Thorbecke GJ, Hochwald GM. The liver as the site of C-reactive protein formation. J Exp Med 1966; 123: 365-378
  • 2 Slaviero KA, Clarke SJ, Rivory LP. Inflammatory response: an unrecognised source of variability in the pharmacokinetics and pharmacodynamics of cancer chemotherapy. Lancet Oncol 2003; 4: 224-232
  • 3 Renton KW. Regulation of drug metabolism and disposition during inflammation and infection. Expert Opin Drug Metab Toxicol 2005; 1: 629-640
  • 4 Aitken AE, Richardson TA, Morgan ET. Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 2006; 46: 123-149
  • 5 Petrovic V, Teng S, Piquette-Miller M. Regulation of drug transporters during infection and inflammation. Mol Interv 2007; 7: 99-111
  • 6 Hiemke C, Baumann P, Bergemann N et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011. Pharmacopsychiatry 2011; 44: 195-235
  • 7 Hefner G, Laib AK, Sigurdsson H et al. The value of drug and metabolite concentration in blood as a biomarker of psychopharmacological therapy. Int Rev Psychiatry 2013; 25: 494-508
  • 8 Haack MJ, Bak ML, Beurskens R et al. Toxic rise of clozapine plasma concentrations in relation to inflammation. Eur Neuropsychopharmacol 2003; 13: 381-385
  • 9 Pfuhlmann B, Hiemke C, Unterecker S et al. Toxic clozapine serum levels during inflammatory reactions. J Clin Psychopharmacol 2009; 29: 392-394
  • 10 Shams ME, Arneth B, Hiemke C et al. CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther 2006; 31: 493-502
  • 11 Greiner C, Hiemke C, Bader W et al. Determination of citalopram and escitalopram together with their active main metabolites desmethyl(es-)citalopram in human serum by column-switching high performance liquid chromatography (HPLC) and spectrophotometric detection. J Chromatogr B Analyt Technol Biomed Life Sci 2007; 848: 391-394
  • 12 Schmitt G, Herbold M, Peters F. Methodenvalidierung im forensisch-toxikologischen Labor. Auswertung von Validierungsdaten nach den Richtlinien der GTFCh mit Valistat. 1st edn. Walldorf: Arvecon; 2003
  • 13 Raaska K, Raitasuo V, Arstila M et al. Bacterial pneumonia can increase serum concentration of clozapine. Eur J Clin Pharmacol 2002; 58: 321-322
  • 14 Abou Farha K, van Vliet A, Knegtering H et al. The value of desmethylclozapine and serum CRP in clozapine toxicity: a case report. Case Rep Psychiatry 2012; 2012: 592784
  • 15 Gründer G, Hiemke C, Paulzen M et al. Therapeutic plasma concentrations of antidepressants and antipsychotics: lessons from PET imaging. Pharmacopsychiatry 2011; 44: 236-248
  • 16 Renton KW. Alteration of drug biotransformation and elimination during infection and inflammation. Pharmacol Ther 2001; 92: 147-163
  • 17 Iber H, Sewer MB, Barclay TB et al. Modulation of drug metabolism in infectious and inflammatory diseases. Drug Metab Rev 1999; 31: 29-41
  • 18 Fogelman SM, Schmider J, Venkatakrishnan K et al. O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology 1999; 20: 480-490
  • 19 McAlpine DE, Biernacka JM, Mrazek DA et al. Effect of cytochrome P450 enzyme polymorphisms on pharmacokinetics of venlafaxine. Ther Drug Monit 2011; 33: 14-20
  • 20 Brosen K, Naranjo CA. Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram. Eur Neuropsychopharmacol 2001; 11: 275-283
  • 21 Fudio S, Borobia AM, Pinana E et al. Evaluation of the influence of sex and CYP2C19 and CYP2D6 polymorphisms in the disposition of citalopram. Eur J Pharmacol 2010; 626: 200-204
  • 22 Yin OQ, Wing YK, Cheung Y et al. Phenotype-genotype relationship and clinical effects of citalopram in Chinese patients. J Clin Psychopharmacol 2006; 26: 367-372
  • 23 Harley J, Luty S, Carter J et al. Elevated C-reactive protein in depression: a predictor of good long-term outcome with antidepressants and poor outcome with psychotherapy. J Psychopharmacol 2010; 24: 625-626
  • 24 Uher R, Tansey KE, Dew T et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry 2014; 171: 1278-1286
  • 25 Unterecker S, Hiemke C, Greiner C et al. The effect of age, sex, smoking and co-medication on serum levels of venlafaxine and O-desmethylvenlafaxine under naturalistic conditions. Pharmacopsychiatry 2012; 45: 229-235
  • 26 Unterecker S, Riederer P, Proft F et al. Effects of gender and age on serum concentrations of antidepressants under naturalistic conditions. J Neural Transm 2013; 120: 1237-1246