10 How valid are therapeutic reference ranges for psychotropic drugs?

Introduction A key principle of Therapeutic Drug Monitoring is the comparison of individual drug concentrations in the blood of a patient to a reference system, the drug-specific therapeutic reference range. Inconsistent methodologies concerning the way that reference ranges were determined has led to a high variation of ranges reported in the literature. Reported ranges from previous guidelines are more or less considered as experts’ opinions [1].

Methods Therapeutic reference ranges yield pharmacodynamic information from a reference population on increased likelihoods for the occurrence of desired drug effects and adverse drug reactions. The presentation will address methodological difficulties, which arise when following this concept. On the basis of examples from the literature, a methodology for finding a therapeutic reference range will be introduced.

Results Most robust method to find a therapeutic reference range is a well-conducted systematic literature review of prospective data. However, prospective studies, showing concentration/response-relationships, are scarce. For most psychotropic drugs, a relationship between drug concentration and therapeutic response is not well established. For these drugs, a preliminary range for referring individual drug concentrations can be, for instance, computed using retrospective data, ideally comprising pharmacodynamic information.

Conclusion The methodology used to estimate the limits of a reference range determines the validity of this range. Valid preliminary ranges can be determined by the use of retrospective data.

Publication History

Article published online:
30 April 2020

• References

• 1 Hiemke C, Bergemann N. Clement, et al. (2018). Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017. Pharmacopsychiatry, 51: 9-62