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The purpose of this study is to determine whether patients who have been prescribed antidepressant medications and have experienced significant adverse effects are more likely to be poor metabolizers on the CYP450 (CYP2B6, CYP2D6, CYP2C19, CYP3A4/5+) drug metabolizing enzymes and/or homozygous for the short allele of the serotonin transporter (SLC6A4) compared to patients who took an antidepressant medication and did not experience significant adverse effects but also had minimal or no response to the medication. The target medications being studied include escitalopram, citalopram, paroxetine, fluvoxamine, venlafaxine, duloxetine, bupropion, vortioxetine, vilazodone, and levomilnacipran only.
Genetic variations in the CYP2B6, CYP2D6, CYP2C19, and CYP3A4/5+ drug metabolizing enzymes are responsible for metabolism of a large number of psychiatric and nonpsychiatric medications. Variations in the genes encoding for these enzymes can alter their activity resulting in unexpectedly high or low serum levels of the drug leading potentially to change in both efficacy and adverse events. The serotonin transporter protein is a presynaptic transmembrane protein responsible for serotonin reuptake. The "short" form of the serotonin transporter promoter (SLC6A4) is associated with reduced activity of the of the transporter. Patients who are homozygous for the "short" alleles of SLC6A4 may be more likely to have with poor response, slow response, and greater adverse events with serotonergic medications. The target medications being studied include escitalopram, citalopram, paroxetine, fluvoxamine, venlafaxine, duloxetine, bupropion, vortioxetine, vilazodone, and levomilnacipran only.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cases | patients who had empirically defined "increased AEs" on one of the specified antidepressants (SSRIs/ SNRIs). This group will get the Genecept Assay, which is a battery of pharmacogenetic tests relevant to psychiatry. |
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| Controls | patients who did not have empirically defined "increased AEs" with an index antidepressant (one of the specified SSRIs/ SNRIs) AND were "nonresponders" to that antidepressant. This group will get the Genecept Assay, which is a battery of pharmacogenetic tests relevant to psychiatry. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genocept Assay | Genetic | battery of pharmacogenetic tests relevant to psychiatry |
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| Measure | Description | Time Frame |
|---|---|---|
| Poor metabolizers have more side effects | Our primary aim is to test the hypothesis that a statistically significantly higher proportion of Cases than Controls will be poor metabolizers on CYP450 isoenzymes (CYP2B6, CYP2D6, CYP2C19, CYP3A4/5+). | through study completion, approximately 2 years |
| Homozygenous for short allele of SLC6A4 will result in more side effects | Our co-primary aim is to test the hypothesis that a statistically significantly higher proportion of Cases than Controls will be homozygenous for the short allele of SLC6A4. | through study completion, approximately 2 years |
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Inclusion Criteria:
5a. Study group: "Increased AEs" currently or in the past on one of the target antidepressants as operationally defined as either A or B: A) One or more AEs that were moderate/severe OR three or more AEs that were mild occurring on less than the usual minimum recommended dose of the antidepressant, or B) Three or more AEs that were moderate/severe OR five or more AEs that were mild on a dose of the antidepressant within the usual recommended dose 5b. Control group: Both A and B A. Less than 30% reduction in the severity of depression after treatment for at least 6 weeks B. Minimal or no AEs on that antidepressant
Exclusion Criteria:
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One hundred (100) subjects aged 18 years or older, currently or in the past on one of the target antidepressants, will be recruited into this study.
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| Name | Affiliation | Role |
|---|---|---|
| William Jangro, MD | Thomas Jefferson University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Thomas Jefferson University | Philadelphia | Pennsylvania | 19107 | United States |
no plan to make IPD available
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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