Vol 7 n°3 - Pharmacology in mood disorders
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Keywords: pharmacogenetics; pharmacogenomics; antidepressant; serotonin; signal transduction
Author affiliations: Psychiatric Clinic of University Munich, Department of Neurochemistry, Munich, Germany

Copyright © 2005 LLS SAS. All rights reserved
Address for correspondence: Prof Dr Brigitta Bondy, Psychiatric Clinic of University Munich, Department of Neurochemistry, Nußbaumstraße 7, D-80336, Munich, Germany
(e-mail: brigitta.bondy@med.uni-muenchen.de)
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P h a r m a c o l o g i c a l   a s p e c t s
www.dialogues-cns.org
Pharmacogenomics in depression and
antidepressants
Brigitta Bondy, MD
Genetic factors are believed to play a major role in the
variation of treatment response and the incidence of
adverse  effects  to  medication.  The  aim  of  pharmaco-
genetics is to elucidate this variability according to hered-
itary differences. Considering current hypotheses for the
mechanisms of action of antidepressants, most investiga-
tions to date have concentrated on mutations in genes
coding either for the pathways in the serotonergic and
noradrenergic systems or for drug-metabolizing enzymes.
Recent studies shifted the emphasis on the main mecha-
nism of drug action from changes in neurotransmitter
concentration or receptor function toward long-lasting
adaptive  processes  within  the  neurons.  Although  the
results are controversial, many studies support the hypoth-
esis that psychopharmacogenetics will help predict an
individual’s  drug  response,  while  minimizing  the  side
effects. The inclusion of functional genomics, which inves-
tigates the complex gene and/or protein expression in
response to a given drug, may lead to the development
of novel and safer drugs.   
© 2005, LLS SAS
Dialogues Clin Neurosci. 2005;7:223-230.
he first antidepressants (AD) were discovered
by chance almost 50 years ago. Despite recent advances
in the discovery and design of ADs, interindividual vari-
ability to treatment remains a serious problem in clinical
psychiatry. It is well known that there are large differ-
ences in dosage requirements and that, with a standard
dose of a given drug, a significant proportion of patients
do not respond satisfactorily while others suffer from
serious adverse effects. In both cases, patients do not ben-
efit  from  the  full  therapeutic  efficacy  and  a  switch
between different treatment regimens is often necessary
to find a more suitable alternative.
The variability in drug response is highly complex and can
be attributed to several physiological and environmen-
tal factors, such as the patient’s age, renal and liver func-
tion, nutritional status, smoking, alcohol consumption, and
physical activity (Figure 1). However, it has been recog-
nized for almost 50 years now that genetic factors also
influence both the efficacy of a drug and the likelihood of
adverse reactions.1 The concept of pharmacogenetics orig-
inated from clinical observations of patients with very
high or very low plasma drug concentrations when given
a fixed dose, and from the discovery that variations in the
DNA   sequences   of   genes   coding   for   metabolizing
enzymes are associated with these discrepancies.
The terms pharmacogenetics and pharmacogenomics are
closely related and often used interchangeably. However,
the terms do have distinct meanings. Pharmacogenetics
represents the variability in drug response and metabo-
lism due to genetic variants, while pharmacogenomics
involves  the  systematic  investigation  of  the  human
genome and alterations in complex gene and protein
expression over time in response to a given drug. There
are,  however,  many   interactions   between   the   two
T