A review of a recently published guidelines' “strong recommendation” for therapeutic drug monitoring of olanzapine, haloperidol, perphenazine, and fluphenazine

Abstract

Introduction In addition to clozapine, there is a growing body of evidence that supports therapeutic drug monitoring (TDM) for additional antipsychotics commonly used in the United States. Methods The Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) published TDM guidelines for several psychiatric medications. Sources were identified that the authors used to establish therapeutic reference ranges for haloperidol, fluphenazine, perphenazine, and olanzapine—4 antipsychotics commonly used in the United States with a “strong recommendation” for TDM. The sources were then reviewed for content and appropriateness for utilization in establishing the reference ranges. Results Olanzapine had 15 citations, haloperidol had 9, perphenazine had 4, and fluphenazine had 2. The studies' methods were reviewed along with the proposed therapeutic reference ranges. Discussion Several limitations of the guidelines were identified. Reference ranges were suggested based on studies of patients with various diagnoses; some patients had an acute exacerbation, and others were in a maintenance phase. An additional publication was identified that reviewed similar (and additional) TDM studies; those conclusions were in slight contrast with those of the AGNP guidelines. In the future, guidance should be given to those looking to conduct TDM studies to standardize methods and make meta-analysis of this data more feasible.

Automated Interlaboratory Comparison of Therapeutic Drug Monitoring Data and Its Use for Evaluation of Published Therapeutic Reference Ranges

“…While a 10–90% range is commonly applied for population-based studies, many report a 25–75 percentile [ 8 , 41 ]. The AGNP consensus guideline does not clearly distinguish between them, and in addition, many of the listed ranges seem to have been concatenated from several studies (both population-based and controlled setups) [ 11 ]. In our experience, the use of a lower fraction can lead to too-narrow ranges.…”

“…The guideline is an impressive and important contribution that lists more than 1300 references, and it is currently in its third edition. However, one point of concern regarding this work is the validity of some of the older citations used to support the ranges herein and the transparency of the calculation of those that have been concatenated from several studies [ 11 ]. Although the variation in the precision between the laboratories has significantly improved over the past 20 years, most published ranges date back to a few early studies performed when the drug was first introduced to the market.…”

Striatal functional connectivity in psychosis relapse: A comparison between antipsychotic adherent and non-adherent patients at the time of relapse

“…To determine whether antipsychotic plasma levels were therapeutic we followed parameters of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) expert group consensus guidelines for therapeutic drug monitoring (TDM), allowing for a maximum of 10% below the lower threshold, since these have indicative purposes only and there is not a correlation between plasma level and efficacy. The cutoffs were 20-60ng/dl for paliperidone, 1-10ng/dl for haloperidol, 0.8-10 ng/dl for fluphenazine, 20-80ng/dl for olanzapine and 100-350ng/dl for aripiprazole 23,24 .…”