In a recently published paper, scientists from Janssen Research & Development and 23andMe report finding a genetic association for the efficacy of the drug bupropion – marketed for treatment of depression under the name Wellbutrin®.
The biological significance of the genetic variant identified in the study is not yet known, and, according to the researchers, will still have to be replicated. But this finding offers intriguing possibilities for future research.
Different Response to Treatments
Major depressive disorder is one of the leading causes of disability and is estimated to affect more than 350 million people worldwide. In the past efforts to understanding the role genetics plays in the condition and its treatment – particularly among patients who do not respond well to current medication – have been hindered by the heterogeneity of the disorder and by studies that until recently have been undersized.
“Genetic predisposition may contribute to the differences in drug-specific, class-specific, or antidepressant-wide treatment resistance,” the authors said. “Clinical studies with genetic data are often limited in sample sizes. Drug response obtained from self-reports may offer an alternative approach to conduct a study with much larger sample size.”
In this study published in the journal Translational Psychiatry, researchers were able to use data from more than 48,000 23andMe customers of European ancestry who completed a survey on antidepressant efficacy and side effects and another 190,000 healthy controls self-reported to be free of any major psychiatric disorders, all of those included in the study consented to participate in research.
The survey that was used to ask customers about the efficacy of treatments for their depression was developed with the assistance of Dr. Steven Hamilton of Kaiser Permanente and Carol Schaffner, from the University of California San Francisco.
The scientists working on this study analyzed the self-reported data from customers to study the effectiveness of three different types of drugs used to treat major depressive disorder. The researchers also included customers who did not report having depression and used them as controls in the study. In each case the study looked at “responders” and “nonresponders” to different treatment and compared them with the healthy individuals who were used as controls.
Currently there are about 30 different prescription antidepressants, many of which affect neurotransmitters in the brain associated with depression.
Although there have been studies that have attempted to look at the role genetics may play in the effectiveness of different treatments, this study is by far the largest effort in that regard.
The three types of medications included in this study were selective serotonin reuptake inhibitors also known as SSRIs; norepinephrine-dopamine reuptake inhibitors, known as NDRIs, which include the drug bupropion (Wellbutrinâ„¢); and citalopram/escitalopram responders.
All of these drugs work by suppressing certain kinds of chemicals in the brain that are associated with depression and are known as neurotransmitters – these include serotonin, norepinephrine and dopamine.
The only association found that met genome-wide significance was for a variant in a region between two genes – GPRIN3 and SNCA. People with the variant had higher odds that treatment with bupropion (Wellbutrin®) would be ineffective. While the function of that gene region is not fully known, the researchers noted that when looking at what is called a “gene set enrichment analysis of buproprion GWAS” they noticed that many of the suggestive associated genes play roles in circadian rhythm and long-term depression pathways. Sleep disturbances are common features of depression, the researchers noted.
The study can be found in the journal Transitional Psychiatry.