Most depressed patients must make multiple attempts before finding an effective antidepressant

UT Southwestern Medical Center psychiatrists are leading a national clinical trial to find biomarkers that can better predict how people suffering from depression will respond to medications so physicians eventually can personalize treatments.

The new trial, launched at UT Southwestern and three other U.S. institutions, is an effort to bring clinical solutions to issues raised by the world's largest depression study, which was conducted by UT Southwestern. That study showed that most depressed patients must make multiple attempts before finding an antidepressant that works best for them.

"Depression is very complex and difficult to treat, and individual differences can impact the way medication works with a particular patient," said Dr. Madhukar Trivedi, professor of psychiatry at UT Southwestern and principal investigator for the study. "Early indicators of whether a treatment is going to work are imperative."

UT Southwestern researchers plan to enroll about 100 of the 400 people needed for the current follow-up clinical study, called EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care). Funded by the National Institute of Mental Health, EMBARC also involves researchers at Columbia University in New York, Massachusetts General Hospital in Boston, and the University of Michigan in Ann Arbor.

The EMBARC study will examine multiple carefully selected clinical and biological markers, using both existing state-of-the-art technologies and pioneering, innovative approaches. Participants initially will undergo magnetic and electroencephalogic brain imaging and blood, DNA, hormonal, chemical, cognitive, and behavioral tests. The 16-week trial then will compare a widely used antidepressant medication to a placebo to trace differences using the same testing technologies.

Major depressive disorder (MDD) is the leading cause of disability in the developed world, and affects nearly 1-in-10 adults in the United States. Doctors currently treat clinically depressed people with a variety of more than 20 Food and Drug Administration-approved medications, which can reduce symptoms for about two-thirds of those treated. But less than a third of these patients fully recover from their depressive episode.

"Which medication is taken makes a big difference to success, but there's nothing to guide physicians in making that choice," said Dr. Trivedi, who leads UT Southwestern's nationally recognized Mood Disorders Research Program and Clinic that studies the neurobiology and psychology of depression and mood disorders.

Dr. Trivedi served as co-principal investigator for the previous study, STAR*D (Sequenced Treatment Alternatives to Relieve Depression). It revealed that as many as 1-in-3 depressed patients try multiple antidepressants before finding one that works. Dr. Trivedi and his group subsequently found that only about 33 percent of those depressed go into remission in the first 12 weeks of treatment with antidepressant medication.

Those who wish to participate in the EMBARC trial can call 214-648-HELP (4357). More information on the trial can be found at

Researchers hope the EMBARC investigation will identify the biomarkers that signal when an antidepressant is working. Evaluation of the usefulness of these markers in a carefully conducted clinical trial comparing an antidepressant to a placebo will help develop a treatment response index that clinicians can use to guide future MDD treatments.


UT Southwestern Medical Center



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