Why Antidepressants May Take Weeks to Show Benefits

by Staff Writer
October 16, 2023 at 10:05 AM UTC

Delayed effectiveness of antidepressants

Clinical Relevance: There’s a new understanding for the delayed effectiveness of antidepressants

  • Researchers explored how the antidepressant escitalopram influences brain connectivity, shedding light on why SSRIs take weeks to work.
  • By observing a protein known as synaptic vesicle glycoprotein 2A, the study focused on the change in synaptic density in two critical brain areas: the neocortex and the hippocampus.
  • While the findings are intriguing, it’s early days. Further research will determine if the concept can lead to better treatments for depression and anxiety.

Scientists may finally understand why antidepressant benefits take several weeks to kick in. And they may also be one step closer to explaining how selective serotonin reuptake inhibitors (SSRIs) actually work. 

Earlier this month, researchers from Copenhagen, Innsbruck, and the University of Cambridge presented a study at the European College of Neuropsychopharmacology (ECNP) in Barcelona. They explored how the antidepressant escitalopram affects the brain in conditions like depression and anxiety.

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SSRI vs. Placebo

The trial involved 32 healthy volunteers. 17 received a daily dose of 20mg of escitalopram, while 15 received a placebo pill with no active ingredient. After three to five weeks, each participant underwent a specialized PET scan to detect a specific protein called synaptic vesicle glycoprotein 2A. This protein serves as an indicator of synaptic density, or the number of connection points, between nerve cells in the brain. 

Essentially, the more synaptic vesicle glycoprotein 2A found in an area, the more synapses are present. As the researchers noted, standard imaging techniques might not offer a high enough level of detail. By focusing on this single protein, the researchers observed the SSRI’s influence on brain connectivity over time.

What the researchers observed was notable. Those on escitalopram experienced a gradual change in synaptic density over time, distinct from the placebo group. It was as if the drug was subtly reshaping the brain’s social network. This suggests that the antidepressant works progressively by altering the connectivity of the brain, and that these changes take a few weeks to become noticeable.

“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,” study author Gitte Knudsen, a clinical professor at Copenhagen University Hospital, said in a press release. 

Essential Brain Regions

Knudsen said that these two key brain regions are pivotal because they both play crucial roles in mental health. The neocortex  takes up around half of the brain’s volume. It’s involved in higher-order brain functions such as sensory perception, reasoning, and complex thoughts and is a critical area for understanding and processing the world. The hippocampus, on the other hand, plays a central role in memory formation and emotional regulation. A region buried within the brain, it’s often associated with conditions like depression and anxiety. 

Identifying an incremental increase in synapses in these specific areas suggests that the SSRI is targeting critical parts of the brain. It also insinuates a biological explanation for why these drugs take time to work.

The findings are compelling but preliminary. According to the researchers, the real test will be determining if these synaptic adaptations are truly the secret sauce for treating conditions like depression and anxiety. They believe that fine-tuning this theory could lead to faster, and perhaps more effective specialized treatments.

The study will be published at a later date in a peer-reviewed journal.

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