Clinical trial NCT01555021: Pharmacogenomics for Antidepressant Guidance and Education
Official title: Pharmacogenomics for Antidepressant Guidance and Education
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Treatment Resistant Depression
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2012-03-15
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study was conducted on the 24-bed inpatient psychiatric unit at Massachusetts General Hospital. Written informed consent was obtained using the MGH-IRB approved consent form. A competency assessment consisting of four questions about the study was obtained. All subjects received a comprehensive psychiatric and medical evaluation including a comprehensive metabolic panel, TSH B12, folic acid, lipid panel and a urine pregnancy test for women of child-bearing age. Subjects needed to meet DSM-IV criteria for major depressive disorder.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change in Quick Inventory of Depressive Symptoms-Self Rating (SR) 16 Item
timeFrame: Measured: Baseline (within 72 hours of admission), once weekly (+/- 24 hours), discharge (7-10 days after admission +/- 24 hours), and 1, 3, 6 months after discharge (+/- 4 weeks)
Secondary outcomes:
measure: Clinician's Report That AGT Modified His/Her Decision Regarding Which Antidepressant to Prescribe.
timeFrame: Measured: +/- 24 hours of baseline assessments and +/- 24 hours of receiving assay results
measure: Treatment Adherence
timeFrame: To determine the impact on adherence of AGT versus TAU at 7-10 days after admission
measure: Adverse Events (Side Effects)
timeFrame: Measures at discharge, 1 month, 3 months, and 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: John D Matthews, MD
role: PRINCIPAL_INVESTIGATOR
References: