9 Influence of comedication on amitriptyline underscore the necessity of TDM

Introduction Amitriptyline is the most prescribed tricyclic antidepressant. It is metabolized by the enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4. Nortriptyline is its active metabolite. Due to the many degradation pathways, multiple interactions are possible, but so far, their extent is largely unknown. In this study, we investigate the impact of certain interactions in TDM measurements of specimens from clinical routine.

Methods The KONBEST TDM-database compromises 1275 measurements of amitriptyline. 1219 of these were accompanied by comedication. The serum levels of amitriptyline and its active metabolite nortriptyline were investigated in the context of comedications with metamizole, lamotrigine or melperone. The concentration-dose-coefficient (C/D) was calculated to compare the concentration independent of the dose.

Results The median C/D for the active moiety of amitriptyline was 1.3 (IQR 0.97). The interactions of amitriptyline with metamizole (N = 46, C/D 0.87, IQR 0.74), lamotrigine (N = 89, C/D 1.41, IQR 0.99), and melperone (N = 44, C/D 1.78, IQR 1.18) were investigated in detail. Only for melperone a significant difference to the monotherapy was found (P-value 0.008). The median number of taken drugs within the investigated samples was 6.

Conclusion Despite the high variability in the measured concentrations, trends due to induction or inhibition effects can be identified. The extent of the pharmacokinetic interactions cannot be predicted exactly, since in most cases a polymedication was present. An analysis of specific interaction pairs is not possible due to the small number of cases. In order to assess the effect of a polymedication in an individual patient, serum level concentration measurement with pharmacological evaluation is necessary.

Publication History

Article published online:
30 April 2020