New Research Reveals How Antidepressants Really Work (Not How We Thought!)

New Research Reveals How Antidepressants Really Work (Not How We Thought!)

For many individuals battling depression, antidepressants are a beacon of hope and a potential path to alleviating their emotional suffering. 

However, they have their downsides. Not least, a long list of side effects plus the fact that they don’t work for everyone. 

Also, rather surprisingly, scientists aren’t quite sure how they work. 

Just last year, a comprehensive review of the research found no evidence that depression is caused by low serotonin levels (the most well-known theory of depression). Researchers admitted that the mechanism by which antidepressants reduce the symptoms of depression is unknown.

However, a new study has shone some light on how antidepressants work.

The study found that antidepressants induce profound physical changes in the brain, facilitating enhanced adaptability and learning over time.

This relatively new idea that the adult brain can grow and adapt is known as neuroplasticity

Neuroplasticity is a promising area of research for mental health disporders as it’s also implicated in the antidepressant effects of psychedelics, lion’s mane mushroom, exercise, and these less conventional practices

The new study 

Presented at the ECNP conference in Barcelona on October 9 and set to be published in a peer-reviewed journal, this groundbreaking study involved 17 healthy volunteers who were administered a daily 20mg dose of the antidepressant escitalopram for a duration of up to five weeks. In parallel, 15 volunteers were given a placebo. 

The researchers employed a PET scanner to gauge the levels of a crucial protein known as synaptic vesicle glycoprotein 2A within the brain. 

This protein serves as a marker, reflecting the brain's plasticity and its capacity for change and learning.

Increased synapses 

The results of this study painted a fascinating picture. 

Volunteers who took the antidepressant displayed a gradual increase in synapses (the site of connnection between two nerve cells) in two important brain regions: the neocortex and the hippocampus. 

The neocortex is responsible for higher cognitive functions like perception, emotion, and reasoning. While the hippocampus plays a crucial role in memory and learning. 

In stark contrast, volunteers who received the placebo showcased no discernible alterations in synapse count.

The researchers attributed their findings to the connection between antidepressants and brain plasticity (neuroplasticity). 

They also postulated that synapses might be pivotal in the mechanism by which antidepressants operate, hinting at the possibility of developing drugs that target synapses more directly. 

Furthermore, they proposed that synapses take time to mature and grow, potentially explaining the protracted duration required for antidepressants to take effect.

Read: 7 Ways To Rewire Your Brain In Weeks

Alternative depression treatments

This study stands as one of the initial pieces of evidence linking antidepressants to brain plasticity in humans, potentially unlocking pathways that can be utilised by other methods.

For example, exercise, psychedelics and lion’s mane mushrooms (among others) have all been shown to increase synapses and plasticity in the brain to exert thier antidepressant effects. 


This 2021 study found that a single dose of psilocybin produced antidepressant effects by increasing the number of synapses in at the brain and enhancing serotonin signalling.

Previous research has found that psilocybin rapidly increases the expression of several genes related to neuroplasticity in the rat brain.

And in 2020, a clinical study found that two sessions of psilocybin-assisted therapy produced significant and lasting antidepressant effects, proving to be more than four times more effective than commonly-prescribed antidepressant drugs. 

Lion's mane mushroom

Lion's Mane mushroom, also known as Hericium erinaceus, which has been used in traditional medicine in Asian countries for centuries, also has a significant impact on the growth of brain cells and neuroplasticity.

Read: 3 Mushrooms Proven To Grow New Brain Cells (Adult Neurogenesis)

A study on mice from earlier this year discovered a compound in lion’s mane, called Hericene A, promotes neuron growth and improves memory.

Other research has found that lion’s mane increases NGF (nerve growth factor), which plays a role in neuroplasticity and neurogeneration (growth of new brain cells).

Natural antidepressants

Exercise, diet, stress relief, mediation, language and instrument learning, socialising, sunlight and novel experiences have also been shown to promote neuroplasticity and to reduce depressive symptoms.  

All this suggests that substances and practices that help the brain to adapt, grow, and even repair itself, potentially offers treatment for mood disorders such as depression and neurodegerative disorders like Alzheimer's disease, as well as brain injuries and even strokes. 

Read: What Is Neurogenesis? (Plus Which Supplements Are Best For Neurogenesis)

Problems with antidepressants

The implications of neuroplasticity are profound, offering hope for more effective treatments for depression, which affects millions worldwide. 

The potential side effects of commonly-prescribed antidepressants are many and range from mild to life-threatening.

On top of that, antidepressants are known to become less effective over time and getting off of them can see withdrawal symptoms and a rebound of symptoms. 

A 2016 paper published in the Patient Preference and Adherence looked at side effects of taking antidepressants long-term.

While those questioned in the study did report less depression and an overall better quality of life, many reported unwanted side effects.The most common were:

  • Sexual problems (72%), including the inability to reach orgasm (65%)
  • Weight gain (65%)
  • Feeling emotionally numb (65%)
  • Not feeling like themselves (54%)
  • Reduced positive feelings (46%)
  • Feeling as if they’re addicted (43%)
  • Caring less about other people (36%)
  • Feeling suicidal (36%)

About 74% of people also mentioned withdrawal symptoms and said they needed support when coming off of antidepressants.

Read: Magic Mushrooms VS Antidepressants


In a world where depression touches so many lives, new developments can help us understand the condition a bit better and give us ideas about how to reduce the suffering associated with it.

Learning that antidepressants work by promoting neuroplasticity suggests we may be able to utilise this mechanism with other substances (like psilocybin and lion’s mane) and practices (like regular exercise and meditation) that come with less side effects than common-prescribed antidepressants.  

As we continue to unearth the intricate workings of neuroplasticity, the future of depression (and other brain disorders such as Alzheimer's disease, brain injury and even stroke) treatment looks increasingly promising.

Read: Can Lion’s Mane Mushroom Help With Depression?


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