To improve psychopharmacotherapy, the expert group of the AGNP issued guidelines for
TDM, in which therapeutic reference ranges (TR), dose related reference ranges (C/D)
and expected drug metabolite to parent drug ratios (M/P) for many psychoactive drugs
are provided to optimize drug therapy. Our study attempted to assess the prevalence
of patients within the anticipated TR for clozapine, olanzapine, or risperidone and
to assess whether the C/D and M/P can be useful to give reasons for drug concentrations
outside the TR.
Clozapine/norclozapine, olanzapine/desmethyl-olanzapine and risperidone/9-OH-risperidone
were gauged in 852 plasma samples of 204 patients (82 female, 122 male; 19 – 76 years)
between 2010 and 2013 under steady state conditions by a validated LC-MS/MS method.
C/D and M/P were calculated in accordance to AGNP-Guidelines. Patients were divided
in groups with and without co-medication and categorized corresponding to median concentrations
from at least 3 up to 5 measurements.
Patients outside TR were preponderantly below the TR. With clozapine (n = 66) only
50% of patients were within, 45% below and 5% above TR, respectively. With olanzapine
(n = 76) most patients (78%) were within, 18% below, and 4% above TR. With risperidone
(n = 62) the majority of patients (66%) was also within TR, 27% below, and 6% above.
Co-medication had no essential effect. An aberrant C/D was noted in 41% of all patients
below the TR. An increased M/P was noted in 23% of patients below TR and a decreased
M/P in 40% of patients above TR.
Our results show that 22% to 50% of medicated patients are not within the TR of their
drugs despite regular TDM. In patients below TR more than half of the cases could
be avowed by dosing errors or non-compliance (C/D) and/or increased drug metabolism
(M/P). Patients above TR had in 40% an inhibited drug metabolism. Our study suggests
that the calculation of C/D and M/P according to the AGNP guidelines can be a useful
tool to better individualize pharmacotherapy in an antipsychotic treatment.