How do antidepressants trigger fear and anxiety?

More than 100 million people worldwide take selective serotonin reuptake inhibitors (SSRIs), such as Prozac and Zoloft, to treat depression, anxiety and related conditions, but these drugs have a common and mysterious side effect: they can worsen anxiety in the first few weeks of use, which leads many patients to stop treatment. Scientists at the University of North Carolina (UNC) School of Medicine have mapped out a serotonin-driven anxiety circuit that may explain this side effect and lead to treatments to eliminate it.

“The hope is that we’ll be able to identify a drug that inhibits this circuit and that people could take for just the first few weeks of SSRI use to get over that hump,” said senior investigator Thomas L. Kash, PhD, the John Andrews Distinguished Professor of Alcohol Studies in the UNC School of Medicine’s department of pharmacology. “More generally, this finding gives us a deeper understanding of the brain networks that drive anxiety and fear behavior in mammals.”

The new study, published in Nature, counters the popular view of serotonin as a neurotransmitter that promotes only good feelings. SSRIs, which are taken by about one in 10 people in the United States and about one in four women in their 40s and 50s, are thought to improve mood by boosting serotonin activity in the brain. There are brain circuits through which serotonin does seem to improve mood, and some studies have linked depression to abnormally low levels of serotonin. But the short-lived promotion of anxiety in many patients on SSRIs – even suicidal thinking, particularly in younger people – has long hinted that serotonin can have negative effects on mood, depending on the precise brain circuit where it acts.

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http://www.psypost.org/2016/08/how-do-antidepressants-trigger-fear-and-anxiety-44581