Don’t throw away your antidepressants just yet

A study published in Nature Molecular Psychiatry is being used to question the use of SSRIs for people with depression. The study involved a new umbrella review of past studies of depression’s relationship with serotonin levels. One major conclusion is that there is no convincing evidence that low serotonin levels are the primary cause of depression. While the review has made headlines for “debunking” the serotonin imbalance theory, it is important not to jump to conclusions on the efficacy of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). 

This new study has led to various articles that have focused on how “scientists have called into question the widespread use of antidepressants.”  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.

A blog entry posted by  Michigan Medicine – University of Michigan on Newswise discusses this recent coverage on antidepressants.

Srijan Sen, M.D., Ph.D., is concerned about the impact of a new study about the role of serotonin in depression that’s getting a lot of attention.

Sen notes that mental health experts certainly don’t believe that a simple ‘chemical imbalance’ is the root cause of depression.

Serotonin is one of the primary brain chemicals, called neurotransmitters, that helps brain cells “talk” to one another by connecting to receptors on cells’ outer surfaces.

The new study that’s getting lots of attention looks at a lot of older studies about serotonin, and tries to draw conclusions by combining the information from them.

The study did not conduct new experiments or even combine previous studies in a meta-analysis. But instead, the researchers conducted an “umbrella review” of some, but not all, meta-analyses related to serotonin.

By coincidence, another such “study of studies” on serotonin and depression was published just a week before the one that’s in the news. It concluded that serotonin transporter gene variations do play a key role in depression risk, in combination with stressful experiences across a person’s life. But that study hasn’t gotten nearly as much attention.

In other words, Sen says, the science of serotonin’s exact role is far from settled.

An article by Ruairi J Mackenzie in Technology Networks explains how this study doesn’t quite debunk years of science, since most scientists don’t adhere to the “chemical imbalance” theory on depression in the first place.

The review article, published by an international research team including first author Prof. Joanna Moncrieff, aimed to assess the available evidence for and against the serotonin theory of depression systematically. The team explain this theory near the start of their paper: “[The theory is] the idea that depression is the result of abnormalities in brain chemicals, particularly serotonin (5-hydroxytryptamine or 5-HT).” The theory has been around for decades, but their overarching conclusion is that it is not correct, given that there appears to be no link between measurable serotonin concentration and depression.

The reaction of many academics to this finding can be summed up, briefly, as “Obviously!” In comments to the UK-based Science Media Centre, Dr. Michael Bloomfield, consultant psychiatrist and head of the translational psychiatry research group at University College London (UCL), said, “The findings from this umbrella review are really unsurprising. Depression has lots of different symptoms and I don’t think I’ve met any serious scientists or psychiatrists who think that all causes of depression are caused by a simple chemical imbalance in serotonin.”

Criticism of the review call into question how these indirect measures of serotonin function or are merely proxies for serotonin activity. They also question how depression is defined since there are multiple factors that contribute to the cause.*

Dr. Michael Bloomfield adds…

What remains possible is that for some people with certain types of depression, that changes in the serotonin system may be contributing to their symptoms. The problem with this review is that it isn’t able to answer that question because it has lumped together depression as if it is a single disorder, which from a biological perspective does not make any sense.

“Many of us know that taking paracetamol can be helpful for headaches and I don’t think anyone believes that headaches are caused by not enough paracetamol in the brain. The same logic applies to depression and medicines used to treat depression. There is consistent evidence that antidepressant medicines can be helpful in the treatment of depression and can be life-saving. Antidepressant medicines are one type of treatment alongside other types of treatment like psychotherapy (talking therapy). Patients must have access to evidence-based treatments for depression and anyone taking any treatment for depression who is contemplating stopping treatment should discuss this with their doctor first.”