18 Optimizing Therapeutic Drug Monitoring (TDM) of mirtazapine – Next step to personalized medicine

Introduction TDM is an effective method to optimize and individualize pharmacotherapy through rapid dose-finding, to minimize side effect and to control for a possible non-adherence. In everyday clinical practice, just the therapeutic index (TI) is applied. However, this only includes an assumed standard dosage without referring to the individual daily dose. Moreover, information about possible abnormal drug metabolism or (partial) non-adherence cannot be deduced from TI. Beyond the TI to obtain a range between which a drug is effective or toxic, we tested following: a) Dose-Related Concentration (DRC) to integrate a patient’s individual dosage into a theoretically expected drug concentration range. b) Metabolic Ratio (MR) to compare metabolite to parent compound concentrations.

Methods In a naturalistic setting, we included 326 inpatients (186 m, 140f; age: 53 years ± 17) treated at the psychiatric hospital of LMU Munich. Referring to the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology (Hiemke et al. 2017) we compared the above calculations (TI, DRC, MR). Serum concentrations of mirtazapine and desmethyl-mirtazapine were quantified by LC-MS/MS. Statistical analyses were performed by using SPSS (25.0).

Results 41 % of the samples had concentrations below the TI (< 30 ng/ml) and 8 % had concentrations exceeding the TI area (> 80 ng/ml). Based on our naturalistic data we redefined these factors [DRC_low = 0.51 and DRC_max = 2.19], covering around 85 % of patients concentrations. 18 samples (5 %) exceeded the MR range (< 0.2; > 1.2).

Conclusion Altogether, only through the interplay of all of these methods (TI, DRC, MR) the therapy can be monitored more precisely, optimized and personalized.

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Artikel online veröffentlicht:
30. April 2020