Researchers Develop Highly Accurate Technique for Predicting Effect of Antidepressants

An international team of researchers that included an investigator from the University of Miami Miller School of Medicine has developed a technique that will predict with 80 percent accuracy whether antidepressants will help patients recover from depression. Charles B. Nemeroff, M.D., Ph.D., Leonard M. Miller Professor and Chair of the Department of Psychiatry and Behavioral Sciences, and researchers from four other institutions in the U.S. and Australia used brain scans combined with a personal history of any early life trauma, such as abuse or neglect, to evaluate the impact of antidepressants on 80 study participants who had been diagnosed with depression. Their findings were published October 10 in an article, “Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants,” in the Proceedings of the National Academies of Science.

“This research is important because at the current time, psychiatrists must essentially use a trial-and-error approach in choosing one of the many antidepressants with different mechanisms of action in treating depression in individual patients,” said Nemeroff, who designed the study and helped with the writing and analysis of the data. “We need to identify predictors of response and non-response, because the longer patients remain depressed, the more likely they are to commit suicide, use illicit drugs and alcohol, and continue to suffer.”

For the trial, participants lay in an MRI machine while viewing images of happy faces and fearful faces on a screen in front of them. Each face triggered brain circuits involving the amygdala, an almond shaped structure involved with the experiencing of emotions. The scans were conducted both before and after an eight-week treatment period with three commonly used antidepressants: sertraline (Zoloft), escitalopram (Lexapro), and venlafaxine (Effexor). Participants also completed a 19-item questionnaire on early life stress, which assessed exposure to abuse, neglect, family conflict, illness or death (or both), and natural disasters before age 18.

The researchers analyzed the pretreatment imaging and the questionnaire to predict how the individual patients would respond immediately after the eighth week of treatment. Using a statistical analysis called predictive modeling, the investigators showed that participants exposed to a high level of childhood trauma were most likely to recover with antidepressants if the amygdala was reactive to the happy faces. Those with a high level of childhood trauma whose amygdala showed low reactivity to the happy faces were less likely to recover with antidepressants.

The researchers say that results from this study could be useful for physicians who usually provide the first line of treatment for patients with depression. They envision the integrated clinic of the future in which physicians ask about childhood trauma and order a five-minute brain scan to help determine the best line of treatment. The study also provides a table that researchers say could ultimately be used by practicing physicians to determine the threshold at which antidepressant treatment is recommended, depending on the varying levels of childhood trauma and brain scan results from patients.

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