How Antidepressants Work and Why Do They Take So Long to Show Effect?

Selective Serotonin Reuptake Inhibitors (SSRIs) antidepressants often take a few weeks before displaying any mental health advantages, but why is this taking so long? A new study by a group of physicians and scientists presents the first human evidence that this is related to physical changes in the brain that result in increased brain plasticity during the first few weeks of SSRI use. This could also help explain one of the methods by which antidepressants function. This work will be presented on October 9th at the ECNP conference in Barcelona (). This work will also be published (accepted) in a peer-reviewed publication.

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How SSRIs Influence Synapse Density Over Time

Doctors have been perplexed as to why Selective Serotonin Reuptake Inhibitors (SSRIs) take so long to work. Researchers from Copenhagen, Innsbruck, and the University of Cambridge conducted a randomised, double-blind placebo-controlled study in a group of healthy volunteers, revealing a gradual difference in the number of nerve cell connections (synapses) between those taking antidepressants and a control group, depending on how long the treatment is given.

17 individuals received a 20mg daily dose of the SSRI escitalopram, while 15 received a placebo. Their brains were scanned with a PET (Positron Emission Tomography) scanner between 3 and 5 weeks after starting the trial, which showed the amount of synaptic vesicle glycoprotein 2A in the brain: this is an indicator of the presence of synapses, so the more of the protein is found in an area, the more synapses are present in that area (i.e., greater synaptic density). These scans revealed significant between-group differences in the evolution of synapse density over time.

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SSRI Intake's Impact on Brain's Neocortex and Hippocampus

Researcher Professor Gitte Knudsen (of Copenhagen University Hospital) said, “We found that with those taking the SSRI, over time there was a gradual increase in synapses in the neocortex and the hippocampus of the brain, compared to those taking placebo. We did not see any effect in those taking placebo".

The neocortex accounts for around half of the volume of the brain; it is a complex brain structure that deals with higher processes such as sensory perception, emotion, and cognition. The hippocampus, which is located deep within the brain, is responsible for memory and learning.

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Synaptic Density Plays a Role in Antidepressant Efficacy

Professor Knudsen continued, “This points towards two main conclusions. Firstly, it indicates that SSRIs increase synaptic density in the brain areas critically involved in depression. This would go some way to indicating that the synaptic density in the brain may be involved in how these antidepressants function, which would give us a target for developing novel drugs against depression. The second point is that our data suggest that synapses build up over weeks, which would explain why the effects of these drugs take time to kick in".

Commenting, Professor David Nutt (Imperial College, London) said, “The delay in therapeutic action of antidepressants has been a puzzle to psychiatrists ever since they were first discerned over 50 years ago. So these new data in humans that use cutting-edge brain imaging to demonstrate an increase in brain connections developing over the period that the depression lifts are very exciting. Also, they provide more Evidence-enhancing serotonin function in the brain can have enduring health benefits.”

References:

1. https://www.bigstockphoto.com/image-475767861/stock-photo-vertical-closeup-cropped-shot-of-depressed-young-woman-taking-antidepressants-pill-at-home-close-up

Source-Medindia