Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram
Information source: Mayo Clinic
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Depression
Intervention: citalopram and escitalopram (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: Mayo Clinic Official(s) and/or principal investigator(s):
David A. Mrazek, M.D., Principal Investigator, Affiliation: Mayo Clinic
Overall contact:
Michelle K Skime, CCRP, Phone: 507-255-0501, Email: skime.michelle@mayo.edu
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.
Clinical Details
Official title: Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram
Study design: Basic Science, Open Label, Single Group Assignment
Primary outcome: The change in HRS-D17 will constitute the major research outcome measure used to assess drug response phenotype because it is widely used in psychiatric research, making it possible to perform comparisons with other studies.
Secondary outcome: QIDS-C16 (obtained by the CRC), and the QIDS-SR16
Eligibility
Minimum age: 18 Years.
Maximum age: 85 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Outpatients or inpatients with nonpsychotic MDD.
2. A score of >14 on the HRS-D17 (equivalent to 10 or greater on PHQ-9 which is used in
primary care to assess depression) given that when medication exceeds the effect of
placebo in primary care participants have a HRS-D17 >12. We added 2 HRS-D17 points to
take into account the possibility of measurement error.
3. Outpatients or inpatients for whom antidepressant treatment is deemed appropriate by
the treating clinician.
4. Subjects who are between 18-85 years of age.
5. Participants who have general medical conditions (GMCs) which could conceivably be
physiologically causing their depressive symptoms will receive treatment as usual for
their GMCs as well as for their MDD.
Exclusion Criteria:
- Subjects with medical contraindications that preclude citalopram or escitalopram
treatment and those who have previously failed to respond to citalopram or
escitalopram will be excluded. In addition, patients with schizophrenia,
schizoaffective disorder, or who have Bipolar I disorder will be excluded because they
have a primary psychiatric condition that requires a different initial treatment.
Subjects currently on antidepressant medication with subtherapeutic results in terms
of depression management will undergo a medication taper and discontinuation prior to
initiation of citalopram or escitalopram treatment. The subject will be closely
monitored by the primary physician or psychiatrist during the medication taper and
discontinuation phase. The medication taper is left upto the treating physician's or
psychiatrist's discretion. Study subjects who cannot be safely tapered from their
medication or experience adverse effects during the taper will be excluded from the
study. Study subjects using their antidepressant medication for management of
nicotine dependence, chronic pain, migraine prophylaxis or other diagnoses will not be
eligible for the study. Trazodone, Melatonin, and Diphenhydramine may be used as
rescue medications for insomnia. Benzodiazepines may be used for treatment of anxiety
and atomoxetine may be used for the treatment of attention deficit disorder. Study
subjects currently on antipsychotic medications (e. g., typical and atypical
antipsychotic drugs) and mood stabilizing agents (e. g., lithium, carbamazepine,
valproate, lamotrigine, gabapentin, or other anticonvulsants) are not eligible for the
study with the exception of those starting quetiapine after baseline. Subjects unable
to give informed consent are excluded. Pregnant subjects will be excluded.
Locations and Contacts
Michelle K Skime, CCRP, Phone: 507-255-0501, Email: skime.michelle@mayo.edu
Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Michelle K Skime, CCRP, Phone: 507-255-0507, Email: skime.michelle@mayo.edu
David A Mrazek, M.D., Principal Investigator
Additional Information
Starting date: March 2005
Ending date: July 2010
Last updated: January 30, 2008
|
