Value and Actuality of the Prescription Information for Therapeutic Drug Monitoring of Psychopharmaceuticals: A Comparison with the Medico-Scientific Evidence

Abstract

Therapeutic drug monitoring (TDM) of psychopharmaceuticals, i.e., the assay of plasma concentrations, is a practical therapeutic application of pharmacokinetic principles in psychiatry. The prescription information (summary of product characteristics, SPC) is provided by pharmaceutical companies according to the requirements of regulatory authorities. The present study investigated the degree of agreement of German SPCs for 48 psychopharmaceuticals with the existing medico-scientific evidence in the area of TDM. For this aim, an empirical summary score of SPC content related to TDM (SPCC (TDM)) was calculated and compared with the level of recommendation of TDM (LOR) of the AGNP-TDM expert group consensus guidelines. Considerable disagreement was found between the information on TDM in SPCs and existing medico-scientific evidence, e.g., in the case of antidepressant and antipsychotic drugs. Even for well studied compounds, such as amitriptyline and clozapine, insufficient information on TDM is included in German SPCs. Small differences existed in the TDM-related information in SPCs of generic drugs with, however, much variance between Germany, Austria and Switzerland. Generally, it must be concluded that deficits exist in the preparation of German SPCs for psychopharmaceutical drugs with respect to empirical pharmacokinetic data, i.e., TDM-relevant information. It is recommended that SPCs of psychopharmaceuticals should be improved in terms of TDM-related information and that target plasma concentrations be adjusted according to the guidelines of the AGNP-TDM expert group. A higher level of good pharmacokinetic practice may be thus achieved.

French summaries of product characteristics: content in relation to therapeutic monitoring of psychotropic drugs

“…The results of SPCC TDM analysis of 59 psychotropic drugs showing the scores for items 1–10, and the sum scores are presented in Table I. For comparison, the SPCC TDM scores from the German study [7] together with the LOR as defined by the AGNP‐TDM [5] group are also listed. It is to note that in the German study, the following drugs were not analysed, but they are also presented in Table I, with their scores: clomipramine, escitalopram, aripiprazole, bromazepam, clonazepam, oxazepam and prazepam.…”

“… d LOR [levels of recommendation 1–5, or not available (–); from 1: TDM strongly recommended, to 5: TDM not recommended] [7]. …”

“…For each drug, a sum score of SPCC TDM was then calculated (maximum value possible 27) and compared with the LOR established by a group of experts (AGNP‐TDM group) [5]. Moreover, the results obtained from the analysis of French SPC were compared with those obtained with the German SPC [7]. For these descriptive comparisons, no statistical tests were used.…”

“…Recently, members of the AGNP‐TDM group [7] studied the degree of agreement of German SPC (‘Fachinformation’) for almost 50 psychotropic drugs with the existing medico‐scientific evidence in the field of TDM. Actually, there was a considerable disagreement between the information on TDM in these German SPC and evidence available from the scientific literature.…”

“…In Western Europe, there are relatively little differences in the availability of drugs introduced into the market for the treatment of psychiatric diseases, but written SPC for the individual drugs differs between the countries. The present study used the identical approach and methodology applied for the investigation carried out to analyse German SPC [7]. Therefore, results obtained from this study were compared with those of the previously reported German SPC analysis.…”