
Why do antidepressants take so long to work?
An episode of major depression can be
crippling, impairing the ability to sleep, work, or eat. In severe
cases, the mood disorder can lead to suicide. But the drugs available to
treat depression, which can affect one in six Americans in their
lifetime, can take weeks or even months to start working.Researchers at the University of Illinois at Chicago have discovered
one reason the drugs take so long to work, and their finding could help
scientists develop faster-acting drugs in the future. The research was
published in the Journal of Biological Chemistry.
Rasenick long suspected that the delayed drug response involved certain
signaling molecules in nerve-cell membranes called G proteins.
Previous research by him and colleagues showed that in people with
depression, G proteins tended to congregate in lipid rafts, areas of the
membrane rich in cholesterol. Stranded on the rafts, the G proteins
lacked access to a molecule called cyclic AMP, which they need in order
to function. The dampened signaling could be why people with depression
are “numb” to their environment, Rasenick reasoned.Samuel J. Erb, Jeffrey M. Schappi, Mark M. Rasenick. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G protein, Gαs. Journal of Biological Chemistry, 2016; jbc.M116.727263 DOI: 10.1074/jbc.M116.727263