Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram
Status:
Completed
Trial end date:
2013-05-01
Target enrollment:
Participant gender:
Summary
This study is one component of a larger U01 grant that was submitted in August, 2004 to the
NIGMS as part of the Pharmacogenomic Research Network. This study will enroll 1200 patients
over 4 years.
It is known that functionally significant genetic polymorphisms for the cytochrome P450
(CYPs) can contribute to individual differences in response to specific selective serotonin
reuptake inhibitors (SSRIs). However, a better understanding of the pharmacogenomics of both
PK and PD for SSRI antidepressants will inform clinical practice. Therefore, we propose to
evaluate the contribution of pharmacogenomics to variation in response to the highly specific
SSRIs citalopram (a racemic mixture) and escitalopram (a chiral compound containing the
active S-isomer of citalopram ) by correlating both PK and PD variation for these agents with
intragene haplotypes in genes encoding proteins involved in citalopram metabolism, as well as
central nervous system (CNS) pathways for monoamine neurotransmitter biosynthesis,
metabolism, storage, release, reuptake, and receptors. In the future this "candidate pathway"
intragene haplotype genotyping strategy will also be complemented by the application of
genome-wide screens performed with DNA from subjects with extreme phenotypes for response to
citalopram.
Phenotypes to be measured before and after the initiation of citalopram or escitalopram
therapy will include determinations of serum citalopram and metabolite concentrations,
treatment response as measured by Hamilton Rating Scale for Depression indices, and number
and severity of side effects as determined by structured questionnaires. The hypothesis to be
tested is that inherited variation in citalopram metabolism and transport (PK) and/or PD
variation as a result of inherited variation in monoamine neurotransmitter biosynthesis,
metabolism, reuptake, storage, receptors or signaling contribute to individual variation in
citalopram antidepressant efficacy and/or side effects.
Phase:
Phase 1
Details
Lead Sponsor:
Mayo Clinic
Collaborators:
National Center for Research Resources (NCRR) National Institute of General Medical Sciences (NIGMS)