Genetic Testing Improves Outcomes for Patients With Depression

May 7, 2018
DNA

NEW YORK CITY—Using combinatorial pharmacogenomic (PGx) testing to guide medication selection for patients with treatment-resistant major depressive disorder vastly improved rates of response and remission, researchers reported at the American Psychiatric Association’s annual meeting.

“Achieving response and remission are fundamental goals of treating patients with mental illness,” wrote John Francis Greden, MD, of the University of Michigan, and colleagues in a poster abstract presented May 7.

“Results from this large-scale, randomized controlled trial demonstrate the clinically significant utility of this combinatorial PGx test in improving short- and long-term response and remission rates in depressed adults compared to clinicians’ usual approaches to medication selection.”

The Profound Potential of Genetic Testing to Transform Psychiatry

genetic testing posterThe double-blind trial randomized 1167 outpatients with treatment-resistant major depressive disorder to either PGx-guided treatment or treatment as usual. Patients were evaluated at weeks 0, 4, 8, 12, and 24 using the Hamilton Depression Rating Scale (HAM-D).

After 8 weeks of treatment, 26% of patients in the PGx-guided treatment group achieved response (defined as a 50% drop in HAM-D score from baseline) and 15% of patients achieved remission (defined as a HAM-D score under 7). In the treatment-as-usual group, 20% of patients achieved response and 10% achieved remission.

Symptom reduction, response, and remission rates continued to improve in the PGx-guided treatment group through the trial endpoint at 24 weeks, the study team reported.

—Jolynn Tumolo

Reference

“Combinatorial pharmacogenomics significantly improves response and remission for major depressive disorder: a double-blind, randomized control trial.” Abstract presented at: the American Psychiatric Association Annual Meeting; May 7, 2018; New York, NY.

Comments

As a psychopharmacologist with a strong background in molecular genetics I am very excited about the future of evidence based and clinically "actionable" pharmacogenomic testing that has the potential to improve clinical outcomes in psychiatry. In my opinion, after an extensive review of this topic, we are not yet at the point where "pharmacogenomic panels" of testing numerous genes is either "evidence based" or "actionable" for clinical practice.

There are individual genes that have crossed the "evidence based" threshold, and can be helpful in specific clinical circumstances. For us in psychiatry, these would include the CYP2D6 gene, CYP2C19 gene, HLA-B*1502 and the MTHFR gene. Fortunately for us cynics, an organization was specifically developed, in partnership with many organizations including the NIH and Stanford University in California, USA to monitor the exponentially growing evidence base for when a particular gene crosses the threshold of evidence base for providing us with clinically actionable information. That organization is the Clinical Pharmacogenetics Implementation Consortium (CPIC)

which states as its mission on its website:

"CPIC’s goal is to address this barrier to clinical implementation of pharmacogenetic tests by creating, curating, and posting freely available, peer-reviewed, evidence-based, updatable, and detailed gene/drug clinical practice guidelines . . . . . .  CPIC guidelines follow standardized formats, include systematic grading of evidence and clinical recommendations, use standardized terminology, are peer-reviewed, and are published in a leading journal (in partnership with Clinical Pharmacology and Therapeutics) with simultaneous posting to [cpicpgx.org], where they are regularly updated."

Significantly, the majority of the genes that are tested in the various commercially available gene panels ARE NOT evidence based, and have not been deemed "actionable" by CPIC. NON-ACTIONABLE genes include the serotonin transporter gene and the serotonin 5HT-2A gene, which many of these panels include in their testing. A vast literature has evolved investigating these 2 genes, but much of the data remains murky and contradictory, with no approval by CPIC as of today. Promoting these multi-gene panels is an unfortunate example of marketing a technology that is not yet clinically evidence based and actionable. If there is a clinical need to test an actionable gene's polymorphic status, the clinician can simply order the phenotyping of that ONE gene (CYP 2D6 is an example of an extremely useful and actionable gene for psychiatrists and pain specialists.

It has been heartening to see a robust dialogue occurring in the psychiatric literature to discuss this important issue.

A timely and comprehensive article can be found in the April 2018 American Journal of Psychiatry's on-line publication:

Clinical Implementation of Pharmacogenetic Decision Support Tools for Antidepressant Drug Prescribing. Zejer Z, Carpenter LL, Kalin NH, et al.  American Journal of Psychiatry. Published online: April 25, 2018  

Thank you for reading this post.

John J. Miller, M.D

www.brain-health.co/