November 29, 2023

New Insights into the Mechanism of Antidepressants: Increased Brain Plasticity Delays Onset of Benefits

New research has shed light on the reason why selective serotonin reuptake inhibitors (SSRIs), commonly used as antidepressants, take several weeks to show any therapeutic effect. A study conducted by clinicians and scientists in Copenhagen, Innsbruck, and the University of Cambridge has revealed that the delay is due to physical changes in the brain, leading to increased brain plasticity over the initial weeks of SSRI intake. This breakthrough discovery offers new insights into the workings of antidepressants and their onset timing.

The study, which has been accepted for publication in a peer-reviewed journal and was presented at the ECNP conference in Barcelona, involved a randomized, double-blind placebo-controlled trial conducted on a group of healthy volunteers. Seventeen volunteers were given a daily dose of 20mg of the SSRI escitalopram, while fifteen volunteers received a placebo. After three to five weeks of treatment, their brains were scanned using a positron emission tomography (PET) scanner to measure the synaptic vesicle glycoprotein 2A, an indicator of synapse density.

The results showed a significant difference between the group taking the SSRI and the placebo group in terms of synaptic density evolution over time. The researchers found that participants taking the SSRI experienced a gradual increase in synapses in the neocortex and hippocampus areas of the brain, while those taking the placebo did not show any effect. The neocortex, which accounts for half of the brain’s volume, is responsible for higher functions such as sensory perception, emotion, and cognition. The hippocampus, located deep in the brain, is vital for memory and learning processes.

Professor Gitte Knudsen from Copenhagen University Hospital, one of the researchers involved in the study, explained, “Our findings suggest that SSRIs increase synaptic density in the brain areas critically involved in depression, providing a potential target for developing novel drugs against depression. Additionally, our data indicate that synapses build up over a period of weeks, which could explain the delayed therapeutic effects of these drugs.”

These findings have been described as exciting by Professor David Nutt from Imperial College London, who was not involved in the study. He stated, “The delay in therapeutic action of antidepressants has been a puzzle to psychiatrists for over 50 years. These new data in humans, which use cutting-edge brain imaging techniques to demonstrate an increase in brain connections as depression lifts, are very exciting. They also provide further evidence that enhancing serotonin function in the brain can have enduring health benefits.”

This groundbreaking research not only explains the mechanism behind the delayed onset of SSRI benefits but also highlights the importance of synaptic density in the neocortex and hippocampus in relation to depression. With this new understanding, researchers can now focus on developing novel drugs that specifically target these brain areas, potentially leading to faster and more effective treatments for depression.


1. Source: Coherent Market Insights, Public sources, Desk research
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