title: Inflammation and psychotropic drugs: the relationship between C-reactive protein and antipsychotic drug levels.
abstract: BACKGROUND
  In psychiatric clinical practice, there is a need to identify psychotropic drugs whose metabolisms are prone to be altered with increased inflammatory activity in an individual patient.
  
  
  OBJECTIVE
  The aim of this study was to find out whether elevated serum levels (≥5 mg/l) of C-reactive protein (CRP), an established laboratory marker of infection and inflammation, are associated with increased serum concentrations of the atypical antipsychotic drugs clozapine, quetiapine, and risperidone.
  
  
  METHODS
  Therapeutic drug monitoring request forms of patients whose antipsychotic drug concentrations had been measured under conditions of normal (<5 mg/l) and pathological (>5 mg/l) levels of C-reactive protein were retrospectively screened. The serum concentrations in relation to the daily doses [concentration per dose (C/D) (ng/mL/mg)] and the metabolic ratios [ratio of concentrations (metabolite/drug)] were compared intraindividually by the Wilcoxon signed rank test. To the study effects of the intensity of infections on drug concentrations, C-reactive protein and C/D levels were submitted to Spearman's correlation analysis.
  
  
  RESULTS
  Elevated levels of C-reactive protein were found in 105 patients. They were significantly associated with elevated values in C/D for clozapine (n = 33, P < 0.01) and risperidone (n = 40, P < 0.01). A trend for an increase was found for quetiapine (n = 32, P = 0.05). Median increases were 48.0 % (clozapine), 11.9 % (quetiapine), and 24.2 % (active moiety of risperidone), respectively.
  
  
  CONCLUSIONS
  In patients who exhibit signs of inflammation or infection with increased C-reactive protein values during psychopharmacological treatment, especially under clozapine and risperidone, therapeutic drug monitoring is recommendable in order to minimize the risk of intoxications due to elevated drug concentrations.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre, Mainz, Germany. gudrun.hefner@unimedizin-mainz.de.|Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre, Langenbeckstrasse 1, 55131, Mainz, Germany. gudrun.hefner@unimedizin-mainz.de.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Hefner
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, University of Mansoura, Mansoura, Egypt.|Department of Pharmacy Practice, College of Health Sciences, Ministry of Health, Muscat, Oman.
authors.forename: Mohamed E E
authors.initials: ME
authors.lastname: Shams
authors.affiliation: Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Unterecker
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre, Langenbeckstrasse 1, 55131, Mainz, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Falter
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical Centre, Mainz, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015415:Biomarkers; D002097:C-Reactive Protein / Q000378:metabolism*; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D011619:Psychotropic Drugs / Q000009:adverse effects* / Q000627:therapeutic use; D000069348:Quetiapine Fumarate / Q000009:adverse effects / Q000627:therapeutic use; D012372:ROC Curve; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D011619:Psychotropic Drugs; D000069348:Quetiapine Fumarate; D002097:C-Reactive Protein; D003024:Clozapine; D018967:Risperidone
keywords: Antipsychotics; C-reactive protein; Clozapine; Drug metabolism; Inflammation; Pharmacokinetics; Psychiatry; Quetiapine; Risperidone; Therapeutic drug monitoring