Why Do SSRI Antidepressants Take So Long To Work? We May Finally Have The Answer
The most commonly prescribed antidepressants, known as SSRIs, often help to relieve the symptoms of major depression. There's just one major caveat: The drugs often take several weeks, or even months, before patients get relief. A recent study now suggests that the cause for this delay may be partly due to signaling problems between important nerve cell membranes, called G proteins.
SSRIs work by making sure the serotonin hormone is transported back to neurons, where it helps put people in a good mood and ultimately ease symptoms of depression. However, as quickly as SSRIs bind to their targets, their effect on a person is slower moving due to an impaired protein signal system. In people with depression, G proteins tend to build up and lose access to a molecule called cyclic AMP, which the proteins need in order to transmit the signals they get from a variety of hormones, including serotonin.
According to lead researcher Dr. Mark Rasenick in a recent statement , the dampened signaling could also be why people with depression are "numb" to their environment. Rasenick discovered this important finding by bathing rat glial cells, a type of brain cell, with different SSRIs and located the G proteins within the cell membrane. He then noted a shift in G proteins out of the lipid rafts.
"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."
Knowing why SSRIs take so long to work could be the first step towards engineering faster-working drugs. The next step is to figure out how to speed up the migration of G proteins out of the lipid rafts in order to help the effects of antidepressants be felt sooner.
Source: Raesnick MM, Erb SJ, Schappi JM. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G protein, Gα s. The Journal Of Biological Chemistry. 2016.