Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01057329 |
| Other study ID # |
223/2008/TDM |
| Secondary ID |
MUW223/2008/2010 |
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 2010 |
| Est. completion date |
March 5, 2019 |
Study information
| Verified date |
March 2019 |
| Source |
Medical University of Vienna |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
The investigators aim to analyse in adolescents with mental illness effectiveness, side
effects, and serum level concentrations of antipsychotics (olanzapine and aripiprazole),
antidepressants (Duloxetine, Atomoxetine) by means of "Therapeutic Drug Monitoring" (TDM) in
order to optimize dosage - effect relations and minimize unwanted side effects.
Description:
We aim to analyse in adolescents with mental illness effectiveness, side effects, and serum
level concentrations of antipsychotics (olanzapine and aripiprazole), antidepressants
(Duloxetine, Atomoxetine) by means of "Therapeutic Drug Monitoring" (TDM) in order to
optimize dosage - effect relations and minimize unwanted side effects.
Therapeutic drug monitoring is becoming a quality measure in psychopharmacotherapy in adults
and children and has been used successfully recently (Hiemke 2008). In 2007, the German Child
& Adolescent Psychiatry University Clinics have founded a network the "TDM-network" headed by
Profs. C. Mehler-Wex and J. Fegert in Ulm (www.tdm-kjp-de). The Viennese Child and Adolescent
Clinic is part of this network. Most importantly, this network must and wants to be
independent from the pharmaceutical industry in order to get un-biased scientific results and
data. Within this network, which has been successfully established in the participating
clinical departments it is possible to take the lead in several scientific areas.
Highest ethical standards, data-protection and rigorous designs are needed to protect
childrens' and adolescents' rights.
Therapeutic drug monitoring (TDM) and its implication for treatment and research: By
definition, TDM signifies the dosage of a drug by controlling its concentration in serum. It
aims at establishing the therapeutical range of the drug given and thus at minimizing the
risk of over- or undermedication (Pschyrembel 2002). Indications for therapeutic drug
monitoring in general comprise the following aspects: - Poor response to the administered
drug despite a clinically established dosage - Severe side effects despite a clinically
established dosage - Combining medications which bear potential to interact adversely with
each other - Treatment of patients at risk (immunosuppression, patients in intensive care,
patients at need of longterm treatment, patients with a high level of comorbidity or genetic
abberations, patients at risk of non-compliance)- Questionable adherence to the treatment
regime -Child and adolescent populations
The scientific background of TDM refers to the assumption that the serum concentration of
substances along with their active metabolites represent a better measure of their
concentration in the brain as the actual dose (Laux & Riederer, 1992; Baumann et al., 2004).
Additionally, it is stated that there is a defined relation between serum concentration and
clinical effect. This correlation could be confirmed e.g. for the tricyclic antidepressants
imipramine und desipramine (Baumann et al., 2004).
Child and Adolescent TDM The psychopharmacotherapy for children and adolescents differs
essentially from adults. It is, in its nature, a developmental pharmacotherapy
(Herpertz-Dahlmann et al., 2003; Gerlach & Warnke 2004). On a somatic basis, the different
developmental stages of children and adolescents, along with their pharmacokinetic variances,
don't allow to use similar dosages as in adult patients.
Pharmacokinetics are essentially influenced by body weight, neurophysiological aspects of
brain development, a factor which is particularly prone to vulnerability in childhood and
adolescence, the gastric milieu and its influence on the uptake of a medication, the
frequency of gastric emptying, the development of connective tissue, the proportional
distribution of body fat, hormone states, liver metabolism, regulation, expression and
function of metabolizing enzymes as well as serum flow in each of the target organs.
Most of the administered drugs, for example, in child and adolescent psychiatry (like
tricyclic antidepressants, SSRIs, typical and atypical antipsychotics) are partly or entirely
catalyzed via the CYP enzymes, which are localized in the liver. Although genetic expression
is limited to the first year of life, regulation and function is largely dependent on the
size of organs and their relation to each other as well as to hormone serum concentrations.
Thus, these factors are liable to change until the end of puberty.
All these aspects are prone to a much greater variance of side effects and of effects in
childhood and adolescence compared to later stages in life (Gerlach et al., 2004).
The vast majority of psychopharmacological agents in child and adolescent psychiatry in
Germany is officially not authorized for this age group (Gerlach et al., 2004). Exceptions
include, for instance, methylphenidate for the treatment of ADHD or the SSRI fluvoxamine,
which can be used for children starting from the age of eight years, for the treatment of
obsessive-compulsive disorder.
Since children and adolescents can't be deprived of pharmacotherapy (given the potential
major benefits seen in clinical practice and with all experience and data from young adults),
the administration of off-label or unlicensed drugs is a practice which is implemented on
wide base. As an obvious consequence, safety and efficacy criteria which are established
under the Medicines Act, don't apply for the patients of concern. Thus, considerable
insecurities among both, medical staff as well as parents (Gerlach & Warnke, 2004), adhere to
psychopharmacotherapy in child and adolescent psychiatry.
Addressing the issue of a need for more efficacy and safety in psychopharmacotherapy for
youth, TDM in childhood and adolescence does not only provide a general indication for the
administration of psychotropic drugs, a field which is largely understudied; it also opens up
the opportunity for assessment and clinical response to individually adjust the dosage of
drug concentration. Overall TDM intends to make the psychopharmacotherapy more evidence-based
and more safe. This is an important issue in this scientific field of medicine which is
desideratum long awaited.
From a scientific viewpoint, standardized studies are needed to assess therapeutic ranges of
plasma concentrations for children and adolescents. Such studies will give an important
insight into the way drugs are metabolized and distributed somatically.
In addition to this, TDM can be considered as a scientifically valid and reliable tool which
contributes essentially to the clinical observation of symptom counts and opens up a whole
new dimension of data based diagnostics and consequently therapy directives. In this respect,
it can be taken as an essential method to improve quality in mental health care among
children and adolescents.
We wanted to ensure and enhance qulaity of psychopharmacological treatment in severe anorexia
nervosa, ADHD and depression.
