PARIS – A 7-day treatment of escitalopram significantly decreased the response of the amygdala to fearful stimuli in adults with major depression, Dr. Beata Godlewska reported at the Annual Congress of the European College of Neuropsychopharmacology.

Previous studies in healthy volunteers using functional magnetic resonance imaging (fMRI) have shown that antidepressant treatment reduces emotional responses to negative stimuli.

"Major depression is characterized by negative biases in emotion processing," said Dr. Godlewska, of the department of psychiatry at the University of Oxford (England). "It has been proposed that this change in processing could mediate the therapeutic effect of antidepressants."

Dr. Godlewska and colleagues randomized 42 depressed adults and 17 healthy volunteers to 10 mg/day of escitalopram or a placebo for 7 days. The researchers collected fMRI image information at a magnetic field strength of 3T on the last day of the study, focusing on activity in predetermined regions of interest for the bilateral amygdala. The imaging data consisted of neural responses to presentations happy or fearful faces, but the participants did not know what responses were being measured.

After 7 days, depressed patients treated with escitalopram showed significantly decreased activation in the right amygdala when presented with fearful faces, compared to depressed patients treated with a placebo. "There was no difference in amygdala activation between the escitalopram-treated patients and the healthy controls," Dr. Godlewska said.

Importantly, no clinically significant changes in mood were observed among the different groups during the 7-day study period, Dr. Godlewska noted.

Therefore, the findings suggest that antidepressants improve a depressed patient’s negative affective bias first, and then mood improves, Dr. Godlewska said. This represents a complete change from the currently accepted thinking. "Now people think that improvement in mood is the first stage, and only then the biases change," she said.

This early improvement in negative affective bias could help depressed patients relearn positive emotional associations in a more supportive environment, Dr. Godlewska noted.

More research is needed to determine the clinical implications of the findings, and Dr. Godlewska and colleagues are currently designing a study that would incorporate long-term follow-up data.

The study was funded by the Medical Research Council. Dr. Godlewska had no financial conflicts to disclose.