Why do antidepressants fail for some?

Research has revealed a biological explanation for why some people with depression do not respond to a class of antidepressants that doctors commonly prescribe. It has to do with fundamental differences in the nerve cells that produce and use serotonin.

New research may explain why antidepressants do not always work.

Serotonin is the chemical messenger that has a major impact on feelings of happiness and wellbeing.

Scientists have long suspected that disruption in serotonin brain circuits is a key factor in major depressive disorder. Selective serotonin reuptake inhibitors (SSRIs) are a significant class of drug that seeks to remedy this disruption by increasing serotonin levels at nerve junctions.

However, for reasons that have been unclear, SSRIs do not work for around 30 percent of people with major depression. Now, researchers from the Salk Institute for Biological Studies in La Jolla, CA, and the Mayo Clinic in Rochester, MN, may have solved the mystery.

Molecular Psychiatry paper describes how, by studying cells from hundreds of people with major depression, the team uncovered differences that could explain resistance to SSRIs.

"These results," says senior study author Fred H. Gage, who is president of the Salk Institute and also a professor in their Laboratory of Genetics, "contribute to a new way of examining, understanding, and addressing depression."

He and his colleagues believe that their findings also offer insights into other psychiatric illnesses that involve disruption of the brain's serotonin system, such as schizophrenia and bipolar disorder.

Depression and nerve cell response to SSRIs

Depression is a leading cause of disability that affects all ages and contributes in a major way to the "global burden of disease," according to the World Health Organization (WHO). The United Nations agency estimate that there are around 300 million people worldwide living with this widespread psychiatric condition.

In the United States, the National Institutes of Health (NIH) suggest that in 2017 around 17.3 million adults, or 7.1 percent of all adults, reported having "at least one major depressive episode" in the previous 12

Published Wednesday 27 March 2019

By Catharine Paddock PhD

Fact checked by Carolyn Robertson