Pharmacogenomics for Antidepressant Guidance and Education
Pharmacogenomics for Antidepressant Guidance and Education
More than one out of three individuals treated for major depressive disorder (MDD) do not
 experience a full reduction of symptoms even when treated with adequate antidepressant
 medication. These individuals may have treatment-resistant depression. This is a condition
 that contributes to the tremendous costs of MDD, in terms of health care costs, functional
 impairment (limitation of an individual's functional ability), and diminished quality of
 life.

 There is a clear need for personalized medicine, for people at high risk for
 treatment-resistant depression. If these individuals could be identified early in the course
 of their depression, they could be recommended for more intensive or specialized
 interventions. Doing so could improve their likelihood of having a full reduction in their
 symptoms.

 Today, there are many treatment options for MDD. Individuals can spend months or years in and
 out of treatment before receiving one that works for their treatment-resistant depression.

 The investigators want to study treatment resistant depression by examining specific genes
 (genotyping) that might influence how your body responds to certain antidepressant
 medications. This process of examining specific genes is not experimental. To look at your
 specific genes, the investigators will collect a blood sample. Genes contain the material
 passed from parent to child that determines the make-up of the body and mind. For example,
 some genes control the color of your hair or eyes. Genes are contained in your DNA
 (deoxyribonucleic acid). There are many differences in DNA, from one person to another. These
 differences may affect a person's chances of having a particular disease.
This will be a 6-month, randomized, controlled study of assay-guided treatment (AGT) versus
 treatment as usual (TAU) in adult inpatients with major depressive disorder. Two hundred
 subjects will be randomized to receive AGT or TAU. After subjects are screened, determined to
 be eligible, and complete baseline assessments, blood samples for genotyping will be obtained
 from all subjects as well as saliva samples for future GWAS analysis from all subjects. Only
 those subjects that are randomized to the AGT arm will have their blood samples immediately
 analyzed. Subjects in the TAU arm will have their blood samples stored for future analysis..

 Once the blood samples are obtained, the attending psychiatrists will be asked to indicate
 their top three choices of antidepressants and at what doses they will initiate treatment. In
 order to prevent delays in providing treatments, the first choice antidepressants will be
 started prior to receiving assay results.

 Upon receiving the assay reports (AGT arm), the attending psychiatrists will be asked whether
 the reports influenced their choice of antidepressant treatments and doses of
 antidepressants, as well as their confidence in their choices. The attending psychiatrists
 will then document any switches in antidepressant treatments or changes in doses of current
 antidepressant medications on a structured form. The assay reports will be available between
 3 to 5 days after the blood samples are taken. The attending psychiatrists who are randomized
 to be provided the results of CYP genotyping will also be provided a phone number for
 consultation with Genomind Labs regarding the interpretation of the results.

 Trough antidepressant blood samples for the AGT arm (10-12 hours after last dose) for
 therapeutic drug monitoring (TDM) will be obtained within 24 hours of discharge. Blood
 samples will also be obtained from the TAU arm, but they will be stored for future analysis
 of CYP genotyping and biomarker analysis of treatment resistant MDD. Clinical follow-up will
 proceed as felt to be clinically indicated. For subjects who have been discharged before the
 assay results are received, the attending psychiatrists will complete the from indicating
 changes in treatments as if patients were still in hospital. Results and recommendations will
 be forwarded to the identified outpatient psychiatrists. (note: blood levels of
 antidepressants were not analyzed)

 The AGT arm is not standard care for patients with depression. The addition of assay-results
 and questionnaires makes the AGT arm different than standard care. Only the questionnaires
 make the TAU arm different than standard care.

 Note:

 Within 24 hours after you are admitted to the Inpatient Psychiatric Unit, the "baseline"
 assessment will occur. If you stay in the Inpatient Psychiatric Unit for more than one week,
 the "weekly" assessment will occur every 7 days. Typically, patients spend an average of 8-10
 days in the Inpatient Psychiatric Unit. The day before or the day of your discharge from the
 Inpatient Psychiatric Unit, your "discharge" assessment will occur. One, 3, and 6 months
 after you are discharged, you will be asked to complete follow-up assessments.
Inclusion Criteria:

 -  Age 18-70

 -  Written informed consent

 -  Meets DSM-IV criteria in the Structured Clinical Interview for DSM-IV-TR (SCID-I/P)17
 and the MINI for current major depressive disorder, without psychotic features

 -  QIDS-SR score of at least 10 (i.e., moderate depression) at initial visit

 -  Failure of at least 1 prior adequate trial of a standard antidepressant (i.e., 6 weeks
 at adequate dose), assessed by the Antidepressant Treatment History Questionnaire
 (ATRQ)18 criteria

 -  Inpatient and expected to remain so for 5 or more days

 -  Hospitalized within past 72 hours

 Exclusion Criteria:

 -  Pregnant women or women of child bearing potential who are not using a medically
 accepted means of contraception (to include oral contraceptive or implant, condom,
 diaphragm, spermicide, intrauterine device, tubal ligation, or partner with
 vasectomy). Immediately after the pregnancy test, women with positive pregnancy tests
 will be unable to enroll in the study

 -  Women who are breastfeeding

 -  Patients who have taken an investigational psychotropic drug within the last 3 months

 -  Section 12 status (involuntary admission)