Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram (PGRN-SSRI)
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|ClinicalTrials.gov Identifier: NCT00613470|
Recruitment Status : Completed
First Posted : February 13, 2008
Last Update Posted : December 18, 2013
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.
|Condition or disease||Intervention/treatment||Phase|
|Depression||Drug: citalopram and escitalopram||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||927 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Pharmacodynamics and Pharmacokinetics of Citalopram and Escitalopram|
|Study Start Date :||March 2005|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||May 2013|
Experimental: Citalopram and escitalopram
Citalopram tablet or solution starting at 20 mg, increase to 40 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.
Escitalopram tablets starting at 10 mg, increase to 20 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.
Drug: citalopram and escitalopram
escitalopram tablets starting at 10 mg, increase to 20 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.
citalopram tablet or solution starting at 2o mg, increase to 40 mg at 4 weeks if QIDS-C16 > 5, keep at same dose if QIDS-C16 < 5.
- 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. [ Time Frame: baseline, 4 week and 8 week visits ]
- QIDS-C16 (obtained by the CRC), and the QIDS-SR16 [ Time Frame: week 0, 4, and 8 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00613470
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Daniel K Hall-Flavin, M.D.||Mayo Clinic|