title: Quetiapine and norquetiapine serum concentrations and clinical effects in depressed patients under augmentation therapy with quetiapine.
abstract: BACKGROUND
  Quetiapine has been recently approved as an add-on therapy in the treatment of major depressive disorders in the case of inadequate response to antidepressant monotherapy. Thereby the antidepressant potential is attributed to the N-demethylated metabolite norquetiapine (NQ). The aim of this cross-sectional analysis was to relate quetiapine (Q) doses to serum concentrations of Q and its active metabolite and clinical effects.
  
  
  METHODS
  Data were obtained from patients who had been treated with different antidepressants and augmented under naturalistic conditions with Q for whom blood level measurements were requested.
  
  
  RESULTS
  For this analysis, 105 depressed patients were included who had been augmented with Q. The mean daily doses of Q were 222 ± 125 mg. Doses correlated significantly (P < 0.001) with the highly variable serum concentrations of both Q and NQ. Median serum concentrations of Q and NQ were 46 ng/mL (25th to 75th percentile 20-91 ng/mL) and 59 ng/mL (25th to 75th percentile 26-133 ng/mL), respectively. Concentrations per dose ranged from 0.10 to 0.58 ng·ml·mg for Q and from 0.17 to 0.59 ng·ml·mg for NQ. Most patients (55%) received comedications in addition to the antidepressant drug and Q. According to the clinical global impressions scale, 60% of the patients were either much (36%) or very much improved (24%). Receiver-operating characteristic analysis revealed no significant differences of serum concentrations between responders and nonresponders for NQ (P = 0.835) but a trend for Q (P = 0.056).
  
  
  CONCLUSIONS
  Due to marked variability of Q and NQ concentrations in the blood, therapeutic drug monitoring may be helpful to identify pharmacokinetic peculiarities. The lack of correlation between serum concentrations of NQ and clinical improvement casts doubts on the concept that NQ is the pharmacologically active principle for the augmentation therapy.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medical center of Mainz, 55131 Mainz, Germany. elnaz.ostadhaji@unimedizin-mainz.de
authors.forename: Elnaz
authors.initials: E
authors.lastname: Ostad Haji
authors.forename: Stefanie
authors.initials: S
authors.lastname: Wagner
authors.forename: Mirijam
authors.initials: M
authors.lastname: Fric
authors.forename: Gerd
authors.initials: G
authors.lastname: Laux
authors.forename: Patrick
authors.initials: P
authors.lastname: Pittermann
authors.forename: Joachim
authors.initials: J
authors.lastname: Röschke
authors.forename: Christoph
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000928:Antidepressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy*; D003987:Dibenzothiazepines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D012189:Retrospective Studies
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; C572724:norquetiapine