Clinical trial NCT00384020: Clinical Pharmacogenomics of Antidepressant Response
Official title: Phase 4 Clinical Pharmacogenomics of Antidepressant Response
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Depression
Keywords: Major Depression Disorder
Antidepressant
Pharmacogenomics
Cytochrome P450
Serotonin Transporter
Lead sponsor: National Health Research Institutes, Taiwan
Sponsor class: OTHER
Collaborators: name: National Science and Technology Council, Taiwan
name: Chang Gung Memorial Hospital
name: Taipei Medical University WanFang Hospital
name: Taipei City Hospital
name: Mackay Memorial Hospital
First posted: 2006-10-04
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Sampling method: NON_PROBABILITY_SAMPLE
Study population: depressive patients in Taiwan

Brief summary: The purpose of this study is to understand how genetic polymorphisms influence the efficacy and side effect profiles of Paroxetine and Escitalopram for major depression treatment.

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 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 Escitalopram (ECIT) or Paroxetine (PAR). It is postulated that mutations affecting the function of SERT will predict responses to ECIT, polymorphism of CYP2C19 will be associated with the side effect profiles and pharmacokinetics of ECIT.

Eligibility criteria: Inclusion Criteria:

* self-identified as of Taiwanese/Chinese ethnic background, and report that both of their parents and all four or three of their grandparents are members of the same ethnic group;
* HAMD-21 \> 17 plus MDE (i.e., current major depressive episode) based on SCID;
* 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;
* age \>= 18;
* capable of giving informed consent;

Exclusion Criteria:

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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: Song-De Branch, Taipei City Hospital
city: Taipei
country: Taiwan
facility: Municipal Wan Fang Hospital
city: Taipei
country: Taiwan
facility: Mackay Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: National Health Research Institutes, Taiwan
name: Keh-Ming Lin, MD, MPH
role: STUDY_DIRECTOR
affiliation: National Health Research Institutes, Taiwan
name: Chia-Hui Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tsai MH, Lin KM, Hsiao MC, Shen WW, Lu ML, Tang HS, Fang CK, Wu CS, Lu SC, Liu SC, Chen CY, Liu YL. Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response. Pharmacogenomics. 2010 Apr;11(4):537-46. doi: 10.2217/pgs.09.168.