Genecept Assay and Adverse Effects of Antidepressants

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.

Inclusion Criteria:

1. Age 18 years or older

2. Able to give informed consent prior to the initiation of any protocol required
procedures.

3. Subject must be able to understand the nature of the study, agree to comply with the
study procedures, and communicate about medical history to the study personnel.

4. Subject was treated with one of the following "target antidepressants:" Escitalopram,
citalopram, paroxetine, fluvoxamine, venlafaxine, duloxetine, bupropion, vortioxetine,
vilazodone, and levomilnacipran. Rationale: These antidepressants are primarily
metabolized by CYP isoenzymes that will be assessed. Antidepressants like sertraline,
fluoxetine, and mirtazapine are metabolized by multiple CYP isoenzymes and therefore
are less likely to be significantly affected by metabolizer status on a particular CYP
isoenzyme. For patients who have been treated with multiple antidepressants, the
antidepressant that was associated with the greatest overall burden of AEs will be
selected as the target antidepressant.

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:

1. Subjects on antidepressants other than those specified in the inclusion criteria.

2. Subjects for whom it is unclear which medication caused the adverse events

3. Subjects for whom participation in the study would be detrimental to their mental of
physical health based on investigator's opinion

4. Subjects who have had a medical condition that, in the investigator's judgment, may be
causing the reported adverse events

5. Prisoners or patients who are involuntarily incarcerated