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|Issue 114||July 2016|
The report is a product of the VA/HSR&D Evidence Synthesis Program.
Evidence Brief: Pharmacogenomics-guided Antidepressant Treatment versus Usual Care for Major Depressive Disorder
Genetic variation has long been explored as a potential contributor to individual differences in antidepressant treatment outcome. Whether using genetic information can help predict how an individual might respond to a particular antidepressant – referred to as 'pharmacogenomics' – is of great interest for further advancing precision medicine efforts. The clinical rationale behind using pharmacogenomic data to inform antidepressant therapy is that a patient's unique genetic profile may help predict whether a patient will tolerate or respond to a drug, or help tailor the dose that will have the best effectiveness and tolerability.
In January 2015, the White House identified VA as a participating agency in the Precision Medicine Initiative, which takes into account individual differences in people's genes, environments, and lifestyles. To inform this initiative, VA's Office of Research and Development (ORD) is developing a clinical study that builds on the Million Veteran Program (MVP) by implementing Precision Medicine in Mental Health (PMH). The PMH committee focused on depression because of its high prevalence, a need for better treatment strategies, and a growing use of genetic testing for decision-making. To inform study development, ORD commissioned the Evidence-based Synthesis Program Coordinating Center (ESP CC) to conduct an evidence brief on the clinical utility of pharmacogenomics-guided treatment for major depressive disorder (MDD).
For this evidence brief, investigators with VA's Evidence-based Synthesis Program located in Portland, Oregon searched the literature through March 2016 and found 15 articles, including two randomized controlled trials, to examine the use of pharmacogenomic testing for antidepressant treatment for adults with depressive disorders. [An evidence brief differs from a full systematic review in that the scope is narrowly defined, and some traditional review methods may be streamlined in order to synthesize evidence within a shortened timeframe.] Specifically, investigators assessed the comparative effectiveness, harms, and cost-effectiveness of pharmacogenomic-guided antidepressant treatment versus usual care.
Summary of Findings
However, all studies involved non-Veterans. Also, most patients in these studies were females in their 40s who lacked comorbidities, such as PTSD, that are common among Veterans who have depression.
The validity of the findings are in some doubt because the studies were small, short-term, have not been replicated, and have numerous minor methodological limitations.
Effects of Following Pharmacogenomics-Recommended Medication Changes
Improving Time to Antidepressant Effectiveness
Optimal Clinical Scenarios for Using Pharmacogenomics-guided Treatment
Moreover, as the duration of follow-up in available studies was only 5-12 weeks, the ORD study should seek to obtain longer-term follow-up of at least 6 months to one year. Longer-term follow-up would facilitate evaluation of maintenance of effects, relapse, and whether pharmacogenomics-guided care could reduce the number of failed antidepressant trials.
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ESP is currently soliciting review topics from the broader VA community. Nominations will be accepted electronically using the online Topic Submission Form. If your topic is selected for a synthesis, you will be contacted by an ESP Center to refine the questions and determine a timeline for the report.
This Management e-Brief is provided to inform you about recent HSR&D findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR&D Resource Center charged with disseminating important HSR&D findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.
This report is a product of VA/HSR&D's Quality Enhancement Research Initiative's (QUERI) Evidence-Based Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers – and to disseminate these reports throughout VA.
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