KING OF PRUSSIA, PA – January 29, 2015 – Clinical depression is a common problem affecting over 16% of Americans at some time in their lives. While antidepressants are among the most common medications prescribed by doctors, large numbers of patients fail to respond to them or have intolerable side effects. Until recently, choosing which medication to give to a patient has been primarily a matter of trial and error. Now, using a small cheek swab or saliva sample of the patient’s DNA, doctors may gain new genetic information regarding how a particular antidepressant may cause side effects or be less likely to help their patient.
Rajnish Mago, MD, Director of the Mood Disorders Program at Thomas Jefferson University, has been conducting research using a battery of genetic tests to provide clues about why some people have more side effects than others or don’t respond to a particular antidepressant. He has just released results of the interim analysis of an ongoing study using the Genecept™ Assay – a genetic panel offered by Genomind, Inc. (King of Prussia, PA). Also collaborating on this study is Sandeep Gupta, MD, a psychiatrist at Christiana Care in Delaware.
The forty-one patients studied so far were all taking one of several commonly used antidepressants whose metabolism depends primarily on two particular liver enzymes, cytochrome P450 2D6 (CYP2D6) and 2C19 (CYP2C19). Cases were defined as patients who had a history of either an unusually large number or severity of side effects to certain antidepressants, and controls were defined as demonstrating virtually no improvement despite taking these medications.
“Even I was surprised by the strength of the results,” said Dr. Mago. “Of the cases who had more than average side effects, 69% had a genetic variation that resulted in a deficient ability to metabolize that particular antidepressant (poor or intermediate metabolism, PM or IM). This would lead to unexpectedly high levels of the antidepressant and, not surprisingly, more side effects. In cases who had two or more severe adverse effects to one of these antidepressants, as many as 87.5% had a genetic variation leading to impaired metabolism. These numbers were triple or quadruple of those in the control group.”
In addition, it was observed that of those patients who were classified as controls/non-responders to an antidepressant, 32% had a genetic variation that lead to an unusually high level of metabolism (ultra-rapid metabolism, UM), thereby reducing the efficacy of the antidepressant. On the other hand, only 6% of those who had a history of significant side effects possessed the genotype for “ultra-rapid” metabolism. Another genetic variation studied leads to low activity of an enzyme called methylenetetrahydrofolate reductase (MTHFR) that is essential for the processing of folic acid from the diet to a form that can be used by the brain. Of controls, those who had not improved on an antidepressant, 20% had this variation, while only 6% of cases had it. Both these findings, however, need further evaluation to clarify if a statistically significant association exists.
The Genecept™ Assay also evaluates genetic variations of the promoter region of the gene encoding for the serotonin transporter, the site where many commonly used antidepressants work. Contrary to some previous research, the “short” and “long” form variations at this location were not associated with either increased side effects or failure to improve with the antidepressant. This may be due to the small size of the study and additional larger studies are warranted to elucidate this finding.
“If these results had been available before the persons took these antidepressants, we could have saved them a lot of suffering and trial-and-error,” said Dr. Mago. “These persons could be given an alternative antidepressant that is not metabolized by the affected enzyme.” While Dr. Mago is continuing to do research in this area, he believes that the time has come for genetic testing to be used routinely in clinical practice to help bring about better outcomes. “Expertise is needed, however,” he warns, “and doctors will need to be trained in how to interpret and apply the results of these tests.”
About the Mood disorders Program at Thomas Jefferson University
The Mood Disorders Program at Thomas Jefferson University provides evaluation and treatment for persons suffering from clinical depression or bipolar disorder, and conducts research related to developing newer treatments that are more effective and/or have fewer side effects. Patients interested in knowing more should call the Mood Disorders Program at (215) 955-9474.
Genomind is a personalized medicine company, comprised of innovative researchers and expert leaders in psychiatry and neurology. Genomind is committed to discovery of the underlying causes of neuropsychiatric disorders and supports the development of personalized medicine that improves patients’ lives. Genomind was founded by Ronald I. Dozoretz, MD, a psychiatrist who has devoted his career to improving mental health. Jay Lombard, DO, a neurologist and co-founder of Genomind, is a critically acclaimed author and nationally recognized thought leader in neuropsychiatry practice and research. Learn more at genomind.com.