Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram
Information source: Mayo Clinic
Information obtained from ClinicalTrials.gov on December 08, 2011
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: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science
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: 507-255-0501, Email: skime.michelle@mayo.edu
David A Mrazek, M.D., Principal Investigator
Additional Information
Starting date: March 2005
Last updated: April 27, 2011
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