June 4, 2008 If a better understanding of genes may lead to customized therapies for schizophrenia, can the same be true for new depression treatments? Answering this question is especially important now that a 2006 government study found that a significant number of people with clinical depression – more than half – are not helped by their initial course of antidepressant treatment, whether medication or talk therapy.
In addition, antidepressant medications often come with troubling side effects, such as sleep changes, sexual problems, headaches and gastrointestinal problems, and an analysis by the Food and Drug Administration has shown that antidepressants may cause suicidal thinking and behavior in children, adolescents and adults ages 18 to 24.
According to Roy Perlis, M.D., M.Sc., the director of pharmacogenomics research at Massachusetts General Hospital’s Department of Psychiatry, specific genes may influence how individual patients respond to antidepressant therapies, which is why his research team is using NARSAD funds to try to find these genes.
After studies in mice identified variations of four genes that may affect how individuals respond to antidepressant treatment, Dr. Perlis and his colleagues examined these four genes in DNA samples provided by 1,554 people participating in a large government study called the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. What the team found was a link between a variation in the gene TREK1 and poorer response to antidepressant treatment.
This is especially significant because people with depression often require more than one treatment before they find one that “works” for them. If individuals with more “treatment-resistant” depression can be identified early in their illness, they may be treated more effectively. Further, Dr. Perlis believes that studying how variations in genes affect response to medications will also lead to a completely new class of more targeted antidepressant therapies.
“Our hope is that one day, we will be able to match patients to those treatments that are most likely to be effective,” Dr. Perlis noted. “When we understand how people respond to different treatments and why, we will be able to design more targeted therapies for depression.”
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