Pharmacopsychiatry 2005; 38 - 69
DOI: 10.1055/s-2005-862682

Pharmacokinetic Variance of Mirtazapine and N-Demethylmirtazapine in Patients Treated for Major Depressive Disorder: A Six Months Therapeutic Drug Monitoring Study

M Reis 1, J Prochazka 2, F Bengtsson 1
  • 1Div. of Clinical Pharmacology, Linköping University, Linköping
  • 2Organon AB, Sweden

Background: Mirtazapine pharmacokinetic (PK) data from patients treated for MDD during a longer period of time has never been investigated. Consequently, in a outpatient study conducted in Sweden, 2000–2002, one of the main objectives was to outline the inter- as well as intraindividual PK variance of mirtazapine (MIRT) and the metabolite N-demethylmirtazapine (NDM) serum concentrations in a heterogeneous naturalistic patient cohort, treated up to six months for MDD.

Material: 192 male and female outpatients aged 18 years or older with MDD according to DSM-IV were included. Repeated serum samples of racemic MIRT and NDM were obtained from the patients at visiting weeks 1, 4, 8 and 24. The result of the TDM analysis, including comments from a clinical pharmacologist, was returned immediately to the treating physician. Altogether 683 serum samples were analyzed.

Results: The median daily dose was 30mg with a maximum dose of 90mg. A pronounced interindividual variability of MIRT and NDM, and the NDM/MIRT ratio was seen. The coefficient of variation was 36%, 33% and 36% respectively. The intraindividual coefficient of variation over time was about 20% on all parameters (all samples trough values in steady state). Women had significantly higher dose corrected concentrations (C/D) MIRT and C/D NDM and NDM/MIRT ratio compared to men. Patients older than 65 years of age had higher dose corrected concentrations than younger patients. Patients with adverse events had lower NDM concentration and lower NDM/MIRT ratio compared to patients with no adverse events. Weight and BMI had a significant negative correlation with NDM concentrations and the NDM/MIRT ratio. Continuous efforts are warranted to perform PK studies in a natural clinical setting in order to learn and understand inter- and intraindividual PK variances in real patients treated for longer periods of time.