Pharmacogenomics for Antidepressant Guidance and Education 1 (PAGE-1_AG1)

A Six-month Study of the Genecept Assay vs. Treatment as Usual to Evaluate Efficacy of Using Assay Guided Treatment in Outpatient Adults With Treatment Resistant Depression

One-third or more of individuals treated for major depressive disorder (MDD) do not experience remission of symptoms despite at least two adequate antidepressant trials. Such treatment-resistant depression (TRD) contributes disproportionately to the tremendous costs of MDD, in terms of health care costs, functional impairment, and diminished quality of life.

The promise of personalized medicine for individuals at high risk for TRD is apparent. If these individuals could be recognized early in their disease course, they could be triaged to more intensive or targeted interventions to improve their likelihood of remission. With the proliferation of treatment options in MDD, at present individuals can spend months or years in and out of treatment before receiving these next-step treatments.

At present, no clinical or biomarker-based tool has been shown to assist in matching patients with treatments most likely to be effective for them. The Genecept Assay offers the possibility of "Personalized Medicine" in psychiatry. Clinicians may find this additional genetic information can lead to optimized treatment plans for individual patients. Before such an assay can be widely applied clinically, it is necessary to demonstrate that this tool usefully impacts treatment outcomes.

This study will examine the potential impact of the assay in terms of depression severity at 3 months, with further follow-up out to 6 months. Secondary measures will allow an estimate of its potential to change clinician behavior and improve patient quality of life. Further measures will also allow for refinement of the assay to maximize patient and clinician satisfaction, and estimate the potential savings associated with deployment of this assay in real-world clinical settings.

Inclusion Criteria:

• age 18-65
• written informed consent
• diagnosis of non-psychotic major depression as determined by study
• clinician/current medical prescriber, and mood disorder diagnosis confirmed by PHQ-9
• 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 (by ATRQ criteria - i.e., 6 weeks at adequate dose)

Exclusion Criteria:

• psychotic features in the current episode, based upon clinical assessment
• 4 or more failed pharmacologic interventions in the current major depressive episode [response rates for these subjects is likely to be extremely low and would require a substantially larger-scale study to identify treatment effects]
• current substance use disorder other than nicotine which based upon clinical assessment requires inpatient or outpatient detoxification
• 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)
• women who are breastfeeding
• serious suicide or homicide risk, as assessed by evaluating clinician
• other unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, based on review of medical history, physical examination, and screening laboratory tests
• patients who have taken an investigational psychotropic drug within the last 3 months