Clinical Pharmacogenomics of Antidepressant Response

• Status: Unknown status
• Trial end date: 2007-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Health Research Institutes, Taiwan
• Collaborators: Chang Gung Memorial Hospital; Jing-Ho Mental Hospital, Taiwan; National Science Council, Taiwan; Taipei Medical University WanFang Hospital; Tsyr-Huey Mental Hospital
• Treatments: Antidepressive Agents; Citalopram; Paroxetine

Criteria

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;