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Why treating depression with commonly prescribed antidepressants takes so long to work

by , 30 August 2017
Why treating depression with commonly prescribed antidepressants takes so long to work
If you suffer from depression, you're familiar with how one day without treatment can feel like a lifetime. A new study published in the journal Neuron explains why treating depression with commonly prescribed antidepressants can take up to six weeks to have an effect…

Doctors have been prescribing serotonin reuptake inhibitors (SSRIs), the most common antidepressants, for depression for decades, but have never been able to determine exactly how they work. For this reason, the researchers behind this study think their findings may one day lead to more effective, faster-acting antidepressants. Keep reading for the full scoop on the findings…

A few years back, the researchers discovered something that led them to carry out this new study…

To get a better idea of how SSRIs work, Paul Greengard’s lab at Rockefeller University in New York City teamed up with Adrien Peyrache, a researcher at the Montreal Neurological Institute and Hospital of McGill University.
 
A couple of years back, Greengard’s lab found that a protein called p11 plays an important role in depression-like behaviours. This protein is strongly expressed in the cholecystokinin (CCK) cells – one particular neuronal subclass in the hippocampus.
 
The tiny neurons help balance the excitation and inhabitation of the network and have a much higher number of receptors to serotonin compared with other neurons of the hippocampus. These findings led first author Lucian Medrihan to believe that examining CCK cells may help learn more about the effects on SSRIs on the brain.

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The new study shows why treating depression with common antidepressants takes weeks to have effects

The team found that serotonin usually inhibits CCK cells, resulting in balanced activity in the hippocampus. They also found that artificially inhibiting CCK leads to the same effects of SSRIs, which suggests that these cells may be a hopeful target for the development of improved antidepressants.
 
Furthermore, the team found that chronic and acute treatment with SSRIs had notably different effects. Serotonin activates different receptors depending on the length of treatment, and long-term treatment resets neural activity, while short-term treatment doesn’t.
 
They said this may explain why treating depression with SSRIs can take a long time to work, despite some fast physiological responses.

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