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Clinical Pharmacogenomics of Antidepressant Response

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ClinicalTrials.gov Identifier: NCT00269334
Recruitment Status : Unknown
Verified December 2005 by National Health Research Institutes, Taiwan.
Recruitment status was:  Not yet recruiting
First Posted : December 23, 2005
Last Update Posted : December 23, 2005
National Science Council, Taiwan
Taipei Medical University WanFang Hospital
Chang Gung Memorial Hospital
Jing-Ho Mental Hospital, Taiwan
Tsyr-Huey Mental Hospital
Information provided by:
National Health Research Institutes, Taiwan

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Major Depression Drug: Using Citalopram(drug) or Paroxetine(drug) Phase 4

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 4 Study of Clinical Pharmacogenomics of Antidepressant Response
Study Start Date : December 2005
Estimated Study Completion Date : November 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants
U.S. FDA Resources

Primary Outcome Measures :
  1. Using the following assessment instruments:
  2. Structured Clinical Interview for DSM-IV Disorders (SCID) at week baseline.
  3. Hamilton Depression Rating Scale (HAM-D) at week 1,2,4,6,8.
  4. Beck Depression Inventory (BDI) at week 1,2,4,6,8.
  5. Clinical Global Impression Scale (CGI) at week 1,2,4,6,8.
  6. Patient's Global Improvement Scale (PGI) at week 1,2,4,6,8.
  7. Treatment Emergent Symptoms Scale (TESS) at week 1,2,4,6,8.
  8. Arizona Sexual Experience Scale (ASEX) at week 1,2,4,6,8.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. self-identified as of Taiwanese ethnic background, and report that both of their parents and all four of their grandparents are members of the same ethnic group;
  2. non-responders: have a 21-item HAM-D score of > 17; partial responders: have a 21-item HAM-D score between 8 and 15; responders: have a 21-item HAM-D score of < 7. Only the non-responder group will be included in Study II.
  3. male or female, who, if of child-bearing potential, agrees to use effective contraception including the regular use of contraceptive pills, intra-uterine devises or abstinence;
  4. age > 18;
  5. capable of giving informed consent.

Exclusion Criteria:

  1. Diagnosis of schizophrenia, schizophreniform disorder, schizoaffective disorder, schizotypal disorder, psychotic depression or bipolar disorders;
  2. current drug or alcohol abuse or dependence or history of drug or alcohol abuse or dependence within the past 6 months;
  3. unstable medical or neurological conditions that are likely to interfere with the treatment of depression;
  4. history of allergy to antidepressants;
  5. history of seizure disorder;
  6. pregnancy;
  7. active suicidal ideation or other safety issues determined by the clinician to not be suitable for inclusion in the study;

Information from the National Library of Medicine

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): NCT00269334

Contact: Keh-Ming Lin, M.D., M.P.H. +886-2-2653-4401 ext 26703 linkeh@nhri.org.tw

Jing-Ho Mental Hospital Not yet recruiting
Kaohsiung, Taiwan, 824
Contact: Ching-Kuan Wu, M.D.    +886-7-6156555 ext 108    wckuan@ms28.hinet.net   
Principal Investigator: Ching-Kuan Wu, M.D.         
TSYR-HUEY(LOVING) Mental Hospital
Kaohsiung, Taiwan, 833
Taipei Municipal Wang-Feng Hospital Not yet recruiting
Taipei, Taiwan, 116
Contact: Dlaire Teng, M.D.    +886-2-2785-8523 ext 53958    claire82@ms26.hinet.net   
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    norase@cgmh.org.tw   
Contact: Chia-Yi Liu, M.D.    +886-3-3281200 ext 3854    liucy752@adm.cgmh.org.tw   
Principal Investigator: Chia-Yi Liu, M.D.         
Principal Investigator: Norase Hsiao, M.D.         
Sponsors and Collaborators
National Health Research Institutes, Taiwan
National Science Council, Taiwan
Taipei Medical University WanFang Hospital
Chang Gung Memorial Hospital
Jing-Ho Mental Hospital, Taiwan
Tsyr-Huey Mental Hospital
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

ClinicalTrials.gov Identifier: NCT00269334     History of Changes
Other Study ID Numbers: EC0931204
NSC 94-2314-B-400 -001 -
First Posted: December 23, 2005    Key Record Dates
Last Update Posted: December 23, 2005
Last Verified: December 2005

Keywords provided by National Health Research Institutes, Taiwan:
antidepressant,major depression,CYP2D6,CYP2C19,SSRI

Additional relevant MeSH terms:
Depressive Disorder, Major
Behavioral Symptoms
Depressive Disorder
Mood Disorders
Mental Disorders
Antidepressive Agents
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Cytochrome P-450 CYP2D6 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors