SSRIs: What Does the Controversial Paper About Their Effectiveness Actually Say?

A recent paper published in July 2022 has been causing waves in the scientific community. It talks about a chemical compound called serotonin, a neurotransmitter that plays a significant role in several bodily functions. These may include regulating mood, cognition, memory, sleep, happiness and even hunger. The results of this study concluded that there is no real association between the markers of serotonin activity and depression - which, in turn, has been deemed controversial, for understandable reasons. 

What is the role of serotonin in regulating mood?

Serotonin is one of the chemicals responsible for transmitting messages across the nervous system. Normal levels of serotonin may help you feel calm, happy and focused. On the other hand, low levels of serotonin have been linked to sadness and anxiety. Medications used in the treatment of depression and anxiety actually work by increasing levels of serotonin in the brain. 

One of the most widely accepted theories within the scientific community is that an imbalance of serotonin in the brain can contribute to depression. To confirm this, a large number of researchers have ventured into studying the role of serotonin in the body. Many drugs in clinical medicine work through unknown or multiple mechanisms, as SSRIs do, which does not affect their safety or efficacy. 

One of the results of this investigation has led to the widespread usage of Selective Serotonin Reuptake Inhibitors or SSRIs. This is a chemical that blocks the brain cells (neurons) from reabsorbing (reuptake) serotonin, making more serotonin available in the intercellular spaces - in between brain cells. This has shown great promise in improving outcomes for people with depression and other disorders.  

Researchers Joanna Moncrieff and Ruth E. Cooper et al, carried out a comprehensive review of the literature that exists on serotonin and its role in depression. The results of this study concluded that there is no association between the markers of serotonin activity and depression.

Although there have been some critiques of the review, psychiatrist and researcher Michael Bloomfield, MD, states: 

"I don’t think I’ve met any serious scientists or psychiatrists who think that all [cases] of depression are caused by a simple chemical imbalance in serotonin. What remains possible is that for some people with certain types of depression… changes in the serotonin system may be contributing to their symptoms. The problem with the review [by Moncrieff et al] is that…it has lumped together depression as if it is a single disorder, which from a biological perspective does not make any sense."

What does this mean?

Most psychiatrists are not worried or surprised by these results. Neuroscientists have known for years that depression is more than a simple imbalance in serotonin levels. But the paper hit a nerve with the general public. It is well known amongst psychiatrists that a complex illness like depression cannot be explained completely just by changes in the concentration of one neurotransmitter. They understand and agree that the mechanisms at play are larger and more complex.  

The problem is probably that the name SSRI - Selective Serotonin Reuptake Inhibitor - for the most typical group of drugs prescribed for depression is misleading one to believe that this is the only mechanism of action at play in depression and its treatment.

The paper reports, “We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.”

This is controversial because the effectiveness of this medication was not scientifically tested in their research - they simply tried to prove that one explanation for the mechanism of action of these medications is not true. The data available suggest that low serotonin levels do not cause depression. However, this does not mean that doctors will stop utilizing antidepressants as a treatment option. Instead, it calls for more research about why antidepressants work the way they do.

Furthermore, the research may impact how we view the use of antidepressants. People may come to view antidepressants more as part of a comprehensive approach to treatment rather than a “fix”, which leads to a more holistic view of the complex condition that depression is. 

This paper brings to light the importance of reading scientific literature in the context of what is written and what it is explicitly trying to prove. A blanket declaration that SSRIs are ineffective in the treatment of depression based on the findings of this paper is misleading. That being said, we do believe that antidepressant treatment should be undertaken conservatively and monitored closely. It should also be regarded as only a single component of a comprehensive, biopsychosocial approach to depression, generally including talk therapy. As such, anyone seeking treatment should be educated regarding all 3 components of mood disorders: biological, psychological, and sociocultural.

Of course, as with all medicine, our psychiatrists will continue to weigh and discuss the risks and benefits with each of our patients, allowing them to make informed decisions as to their preferred treatment plans.