Scientists Reveal Why Antidepressants Take So Long to Work

New research presented at the European College of Neuropsychopharmacology (ECNP) Congress suggests SSRI antidepressants may have a specific action in the brain that takes time to evolve.

The most common treatments for depression include psychotherapy and antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). However, when a person begins taking an SSRI, it often takes weeks to notice any mental health benefits.

This phenomenon has mystified scientists since SSRIs first entered the scene as a depression treatment option in the late 1980s.

Recently, scientists from Copenhagen, Innsbruck, and the University of Cambridge found more clues as to how antidepressants work and why people taking these medications experience a delay in symptom relief.

The scientists presented the results of their randomized controlled trial on October 9 at the 36th European College of Neuropsychopharmacology (ECNP) Congress in Barcelona, Spain. The presentation precedes the study's publication in a peer-reviewed journal.

How do antidepressants work?

To investigate the inner workings of SSRIs in the brain, the researchers started 15 healthy participants on a placebo and 17 healthy participants on a 20mg daily dose of escitalopram — an SSRI commonly known under the brand Lexapro.

Then, the participants underwent brain scans between three to five weeks after taking the medication or placebo. Specifically, they had positron emission tomography (PET) scans, which can show indicators of nerve cell connection or synapse density within brain regions.

After examining the scans, the scientists found that participants taking escitalopram had gradual increases of synapses in the hippocampus and neocortex regions of the brain.

The neocortex is a significant brain area responsible for emotion, cognition, and sensory perception, and the hippocampus plays an important role in memory, learning, and motivation.

However, the researchers found no brain changes among those taking a placebo.

These findings suggest synaptic plasticity in a healthy person's brain evolves over the first few weeks of SSRI administration.

"This points towards two main conclusions," explained study author Professor Gitte Knudsen of Copenhagen University Hospital, in a news release. "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."

Knudsen also says synapses build up over a period of weeks, which explains the wait time in which these drugs kick in.

Though more studies are needed involving participants with depression, the authors say this is the first evidence in humans to support the theory that SSRIs act on neuroplasticity in the brain and could explain why it takes a few weeks for antidepressants to ease symptoms.

What to do while waiting for an antidepressant to work

Although SSRIs and other antidepressants take time to kick in, implementing a few self-care strategies into the daily routine can help manage the symptoms of depression. For example, eating a healthy diet that boosts a healthy gut biome and provides adequate nutrients like omega-3 fatty acids and vitamin B may help combat depression and anxiety.

It may also be helpful to avoid food and drinks that contain alcohol, caffeine, and sugar because these compounds can worsen symptoms.

Moreover, prioritizing sleep and getting enough exercise can go a long way in boosting mood and mental wellbeing.

In addition, a person could consider visiting a therapist, as adding psychotherapy to the depression treatment plan can be an effective strategy to manage depression while waiting for the antidepressant to work.


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