472
tracked their response to a course of antidepressant drugs. They found three com-
mon variations in the human version of sFRP3 that were linked to a better response
to therapy. Search of a database that correlates gene sequences to gene activity in
the human brain revealed that all three variations caused less gene activity. sFRP3
is also regulated by other conditions, including exercise. sFRP3’s activity is very
sensitive to the amount of activity in the brain. This fi nding could lead to genetic
tests that enable physician’s to predict a patient’s response to antidepressants, and it
also provides a target for potential new therapies for the disease.
Treatment Resistant Depression
The Massachusetts General Hospital (Boston, MA) started a major study in 2012
aimed at guiding treatment of patients suffering from treatment-resistant major
depressive disorder. The study is using genetic biomarker data to compare standard
treatment with that guided by Genomind’s Genecept assay, which combines a pro-
prietary panel of genetic tests with an analytical report to clinicians. The primary
objective of the study is to improve depressive symptoms from baseline to 6 months.
Other goals are to change clinician behavior and reduce costs. Researchers will
focus on pharmacogenetic genotyping of metabolic activity, which can then be used
to guide treatment of patients with antidepressants. Also, genome-wide association
study analysis will be performed in the future to identify biomarkers that may be
predictive of patient response to and tolerance of certain therapeutics.
Vilazodone with a Test for Personalized Treatment of Depression
Vilazodone (Clinical Data’s VIIBRYD®), a dual SSRI and a 5HT1A partial agonist,
is in phase III development in parallel with genetic biomarkers to guide its use as an
antidepressant. As approximately one-half of depressed patients do not achieve satis-
factory results with current fi rst-line treatment options, a product that combines a
genetic test with vilazodone will assist physicians in matching patients with a drug
that is more likely to be effective for each patient in the fi rst instance. The primary
and supportive secondary effi cacy endpoints were met in a randomized, double- blind,
placebo-controlled trial. In addition, the study separately identifi ed candidate bio-
markers for a potential companion pharmacogenetic test for response to vilazodone.
Personalized Management of ADHD
Attention defi cit hyperactivity disorder (ADHD) is one of the most common neuro-
psychiatric disorders in children and adolescents. Many different medications are
available to treat ADHD, yet little data exists to guide treatment choices, which
often must be based on trial and error. Stimulant medications, such as methylpheni-
date are the most commonly used, effective treatment for ADHD.
13 Personalized Management of Psychiatric Disorders