It is comfortable to believe that science has all the answers and that our medical professionals are acting with a complete understanding of the human body and mind. However, even today when we know more about the world than ever, there is still much that is a mystery. Science, as a pursuit of knowledge and growth, always arises to say that things weren’t quite what we thought. New studies are constantly laying havoc on what we think we know, and the long beloved theory of what causes depression is the most recent thing to hit the chopping block.

A review published at the end of July brings into question the long-believed theory that depression is caused by chemical imbalances in the brain. This theory began to take root in the 1950s and 60s through a handful of scientific studies and publications that suggested low serotonin levels may cause depression. The theory stuck and became the backbone for the treatment model for major depressive disorder that we still use today. 

In the 70s, scientists began to develop Selective Serotonin Reuptake Inhibitors (SSRIs) for the treatment of depression. SSRIs prevent the reabsorption (reuptake) of serotonin transmitters in the brain, thus increasing the levels of serotonin. In the 90s, SSRIs became the standard treatment for the rising cases of depression. Popular SSRIs such as Prozac and Lexapro have even advertised that chemical imbalances in the brain ‘may’ cause depression.

Anti-depressant use is higher than ever, SSRIs being the most popular. Between 2015 and 2018, the CDC reported that 13.2% of Americans had used anti-depressants. During the pandemic, there was a 21% rise in anti-depressant, anxiety, and insomnia prescriptions. 

Today, an estimated 80% of people still believe that depression is caused by a chemical imbalance in the brain, yet this new study shows that the evidence to support that claim is lacking.

The Review

Everybody has been talking about the scientific review that has thrown out the chemical imbalance theory, but it is not quite as decisive as many click-bait articles would like you to think. So, let’s take a look at what the review covered and what it means.

Several European researchers did an umbrella review of studies previously published on the relationship between serotonin levels and depression. The researchers found 17 systematic reviews and meta-analyses that met the criteria that they laid out to answer the question: do low serotonin levels cause depression? They only took into account the most recent studies and had comprehensive guidelines for what the studies and reviews needed to be included.

Systematic reviews and meta-analyses are both structures in which studies that have previously been done are analyzed for efficacy. They are designed to eliminate bias to form sound conclusions. They judge the viability of a study (systematic review) or a set of studies (meta-analysis). Though these structures intend to make an unbiased analysis of a body of work, that is not always the case. 

Of the 17 reviews and analyses that were chosen, “Only 31% adequately assessed risk of bias in individual studies.” Upon full analysis of all the data, the review found that there is insufficient evidence to conclude that chemical imbalance is the cause of depression. They found in many studies that the difference in serotonin levels was not significant enough to confirm the hypothesis. In one study, there was evidence that serotonin levels were higher in those who reported depression, however, most of the subjects had a history of taking SSRIs so those results are inconclusive. 

The conclusion– there is not enough evidence to support the chemical imbalance theory and more research is needed to establish what causes depression.

Utilizing the Psychedelic Model

This review leaves us back where we were before, wondering what exactly causes depression. Only now there are more tools to help broaden the search for solutions. Psychedelics can be used as a research tool to build new theories around unanswered questions about the human mind.

At the beginning of psychedelic research, back in the 50s, it was led by curiosity to better understand the mind and mental health. When LSD was first synthesized and distributed, scientists and psychotherapists believed that it gave them insight into the minds of schizophrenic and psychosis patients. That theory was eventually discarded and the term psychedelic, meaning “mind revealing” was adopted. 

This idea that psychedelics can help scientists better understand the mind could prove useful in moving forward to discover what truly causes mental health issues like depression. Recent studies into psychedelic treatment for depression have shown promising results. Psychedelics increase neuroplasticity. This makes the brain more susceptible to changes in thought and behavioral patterns. They also help uncover buried traumas so that patients can work through them. These aspects make it a valuable tool for providers to use along with traditional forms of psychotherapy. However, much is still not understood about why they are so effective. 

Psychedelics offer scientists unique insights into the mind and various mental health conditions. There is an opportunity right now to start looking at depression in new ways and find creative solutions and theories as to what causes it. People who take psychedelics often report a feeling of “oneness” or “connectedness.” This concept could be used to encourage researchers to look at depression as a symptom of a lack of connectedness of the mind, body, and environment. This new review opens up the doors for a paradigm shift. It is time for the merging of new and old ideas to find the best treatments for depression and other mental health challenges. 

What’s Next in Treating Depression?

SSRIs have been a big part of treating depression for a long time, and that isn’t going to change overnight. Many patients find success with SSRIs. However, it is now clear that scientists don’t know why. That is not unusual. Many medications show great results without a complete understanding of why they work. This leaves way for new theories on what causes depression, and new treatments.

Standard depression medications can have side effects such as sleep issues, weight gain/loss, and nausea. With little to no side effects, psychedelics could be a good option for the 40% of people who have not found success with traditional treatment methods. 

The doors are open for new creative solutions, and it couldn’t have come at a better time for psychedelics. With old beliefs on what causes depression being shed, there is room for new treatments, like psychedelics, to enter the space and work with existing models to create even more effective treatments.