Antidepressants get backed up in the brain, delaying their effects, study says

The drugs take weeks to months to work, but researchers say the new understanding of their function could speed

By Stephen Feller

CHICAGO, July 28 (UPI) -- Selective serotonin reuptake inhibitor antidepressants can take weeks or longer to work for patients, leaving researchers to wonder why while searching blindly for ways to speed them up.

SSRI drugs build up in the lipid layers of nerve-cell membranes, helping other proteins function better, before their effects can be felt by patients, according to researchers at the University of Illinois at Chicago, who say there may be ways to speed up the action of the drugs.


People with depression are thought to have too little serotonin released into their brains. SSRIs bind to structures in nerve cells involved with passing serotonin back and forth between neurons. When serotonin is released into the synapse, SSRIs prevent it from being taken back into the neurons -- amplifying its effects and reducing symptoms.

Previous research at the University of Illinois showed signaling molecules in nerve cells called G proteins congregate in the lipid layer of cell membranes, seeking a molecule called AMP in order to function. According to the researchers, this molecular malfunction causes the "numb" feeling depression patients often report.

"It's been a puzzle for quite a long time why SSRI antidepressants can take up to two months to start reducing symptoms, especially because we know that they bind to their targets within minutes," Dr. Mark Rasenick, a distinguished professor of physiology and biophysics and psychiatry at the University of Illinois, said in a press release.


For the study, published in The Journal of Biological Chemistry, researchers tested several SSRI drugs on rat glial cells, finding that over time the drug replaced G proteins in the lipid layer -- allowing the protein to access the AMP molecule.

"The process showed a time-lag consistent with other cellular actions of antidepressants," Rasenick said. "It's likely that this effect on the movement of G proteins out of the lipid rafts towards regions of the cell membrane where they are better able to function is the reason these antidepressants take so long to work."

Rasenick said future research should focus on determining exactly where SSRI drugs bind to neurons, with the goal of helping them speed the ejection of G proteins from the cellular lipid layer and allow the drugs to work faster.

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