Clinical Pharmacogenomics of Antidepressant Response
Recruitment status was Not yet recruiting
The study includes two components：(1) cross-sectional (Study I), and (2) longitudinal treatment trial (Study II). The cross-sectional component will include all subjects initially recruited for the parent project. Genotyping characteristics will be compared with clinical status (i.e., recovered vs symptomatic). The treatment trial component (one) will include a subset of the subjects (n = 400) who remain significantly depressed. They will be randomly assigned to 8-weeks of treatment with either citalopram or paroxetine. With such a design, we wish to test the following hypotheses：
Ⅰ. Depressed patients with the short variant of the serotonin transporter (5HTTLPR) will respond faster and better to antidepressants compared to their counterparts with the long variant. Concurrently, patients with the 5-HTT Stin2 12/12 allele will also show better response as compared to those with the 10/12 allele.
Ⅱ. Depressed patients who are homozygous for deficient or less active CYP2D6 or CYP2C19 enzyme(s) will be more likely to show treatment emergent side effects compared to subjects with the wildtype alleles. Specifically, in Study II, CYP2D6 polymorphism will predict PAR but not CIT side effects and CYP2C19 polymorphism will be associated with CIT but not PAR side effects.
Drug: Using Citalopram(drug) or Paroxetine(drug)
|Study Design:||Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 4 Study of Clinical Pharmacogenomics of Antidepressant Response|
- Using the following assessment instruments:
- Structured Clinical Interview for DSM-IV Disorders (SCID) at week baseline.
- Hamilton Depression Rating Scale (HAM-D) at week 1,2,4,6,8.
- Beck Depression Inventory (BDI) at week 1,2,4,6,8.
- Clinical Global Impression Scale (CGI) at week 1,2,4,6,8.
- Patient's Global Improvement Scale (PGI) at week 1,2,4,6,8.
- Treatment Emergent Symptoms Scale (TESS) at week 1,2,4,6,8.
- Arizona Sexual Experience Scale (ASEX) at week 1,2,4,6,8.
|Study Start Date:||December 2005|
|Estimated Study Completion Date:||November 2007|
Despite remarkable progress in recent decades in modern psychopharmacotherapy, patients vary substantially in their response to antidepressants, ranging from total remission to complete treatment failure. Adverse effects, often bothersome and occasionally life-threatening, continue to represent significant challenges to patients and clinicians. Mechanisms responsible for such variability remain poorly understood. In addition, although less appreciated, substantial cross-ethnic variations in psychotropic responses often exist. Recent developments in the field of pharmacogenetics indicate that genetic factors may account for a large part of these differences in response. Specific genetic polymorphisms affecting the function of the serotonin (SERT) system has been postulated to predict the effect of antidepressants. Similarly, genetic mutations have been shown to exert a predominant influence on the expression of a number of drug-metabolizing enzymes, including most of the cytochrome P-450 enzymes (e.g., CYP2C19 and CYP3A4) that are responsible for the biotransformation of most antidepressants. Polymorphisms of genes controlling these enzymes have been found to be strongly associated with the propensity for various kinds of side effects. Capitalizing on these new developments, the proposed study will examine the predictive value of some of these genetic polymorphisms in 400 patients with DSM-IV major depression prospectively treated with citalopram (CIT). It is postulated that mutations affecting the function of SERT will predict responses to CIT, polymorphism of CYP2C19 will be associated with the side effect profiles and pharmacokinetics of CIT. The proposed study represents an extension and replication of a 5-year NIH/NIMH collaborative project that had designed and initiated in 2001 by the PI, which is currently ongoing at three sites in the U.S. ( “Ethnic Variations in Antidepressant Response” 1 R01 MH62421; 1R01MH626761R01MH62531, 07/01 - 06/06). In the original study, the inclusion of the two comparison groups, African Americans and Caucasians, whose genetic mutation patterns diverge significantly from each other, will allow us to examine how these differences affect their antidepressant response patterns and whether the associations are “replicable” across ethnicity. Results will be pooled with those derived from other sites, and will represent a rare opportunity to compare findings across Taiwanese, African American and Caucasian subjects with comparable diagnosis and treated with an identical protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00269334
|Contact: Keh-Ming Lin, M.D., M.P.H.||+886-2-2653-4401 ext email@example.com|
|TSYR-HUEY(LOVING) Mental Hospital|
|Kaohsiung, Taiwan, 833|
|Jing-Ho Mental Hospital||Not yet recruiting|
|Kaohsiung, Taiwan, 824|
|Contact: Ching-Kuan Wu, M.D. +886-7-6156555 ext 108 firstname.lastname@example.org|
|Principal Investigator: Ching-Kuan Wu, M.D.|
|Taipei Municipal Wang-Feng Hospital||Not yet recruiting|
|Taipei, Taiwan, 116|
|Contact: Dlaire Teng, M.D. +886-2-2785-8523 ext 53958 email@example.com|
|Contact: Winston Shen, M.D. +886-2-2785-8523 ext 53958 shenwinw@AOL.com|
|Principal Investigator: Claire Teng, M.D.|
|Principal Investigator: Winston Shen, M.D.|
|Chang-Gung Memorial Hospital||Not yet recruiting|
|Taoyuan, Taiwan, 333|
|Contact: Norase Hsiao, M.D. +886-3-3281200 ext 3854 firstname.lastname@example.org|
|Contact: Chia-Yi Liu, M.D. +886-3-3281200 ext 3854 email@example.com|
|Principal Investigator: Chia-Yi Liu, M.D.|
|Principal Investigator: Norase Hsiao, M.D.|
|Principal Investigator:||Winston Chen, M.D.||Taipei Municipal Wang-Feng Hospital|
|Principal Investigator:||Claire Deng, M.D.||Taipei Municipal Wang-Feng Hospital|
|Principal Investigator:||Jia-Yi Liu, M.D.||Chang Gung Memorial Hospital|
|Principal Investigator:||Norase Hsiao, M.D.||Chang Gung Memorial Hospital|
|Principal Investigator:||Jung-Kuang Wen, M.D.||JSYR-HUEY(LOVING) Mental Hospital|
|Principal Investigator:||Ching-Kuan Wu, M.D.||Jing-Ho Mental Hospital|