Pharmacopsychiatry 2022; 55(03): 166
DOI: 10.1055/s-0042-1747651
Abstracts | XIVth Symposium of the Task Force Therapeutic Drug Monitoring of the AGNP

How valid are therapeutic reference ranges for psychotropic drugs?

X.M. Hart
1   Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
G. Gründer
1   Department of Molecular Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
C. Hiemke
2   Department of Psychiatry and Psychotherapy, University of Mainz, Mainz, Germany
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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 The most robust method to find therapeutic reference ranges is a well-conducted systematic literature review including a meta-analysis of prospective data. However, prospective studies, showing concentration/response-relationships, are scarce. It will be presented that 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 population-based concentration ranges. In this context, retrospective data, ideally comprising pharmacodynamic information, can be helpful.

Conclusion The methodology used to estimate the limits of a reference range determines the validity of this range. Valid ranges do not solely base upon single (concentration efficacy) studies. Recommendations should also consider insights from e.g., TDM and neuroimaging studies. Validation studies of ranges that are currently in use are past due.



Publication History

Article published online:
16 May 2022

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