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Expert highlights the link between serotonin, SSRIs and depression

Updated: Apr 17

thinking depression man on couch

Press Release

Date: 18 January 2023

According to some reports, there has been increasing concern about the role of serotonin in moods and whether SSRI’s work as a treatment. The research which featured in Molecular Psychiatry reviewed 17 studies and found people with depression didn’t appear to have different levels of serotonin in their brains to those without. 

This in turn questions the theory of how the drugs might work – by correcting a deficiency.

We spoke to expert, Senior Psychiatrist Dr James Woolley at Schoen Clinic Chelsea in London to find out more about the research and whether it will have an impact on the use of SSRI’s in treating depression.

headshot of James Woolley, Consultant Psychiatrist in London, man wearing a grey suit and pink tie smiling at camera

Is depression a chemical imbalance? What could be the other biological factors predisposing for depression?

It has long been thought that there are differences in some people’s levels of serotonin in the brain, and that in some cases this may predispose to depression.  This research has been one of the reasons given why medication which increases effective serotonin levels can help improve depressive symptoms.  These sorts of medications, commonly known as SSRIs are very widely prescribed within hospitals and GP surgeries alike, so if there is a suggestion they may not even work, then this is big news.

The research was something of an oversimplification when the study was reported in the press concluding that, "antidepressants do not work", are little different from placebos, and, rather than improve depression, just "numb emotions".  As well as not being supported by a great deal of other scientific studies, without a more balanced discussion there was the risk of people suddenly stopping antidepressants which they had taken without difficulty, sometimes for a long time, leading to withdrawal symptoms and risking a return of their depression.

More balanced reading of the evidence reveals that there is good evidence from large, well conducted studies clearly demonstrating that antidepressants are effective in treating people with new episodes of depression-and not just due to the placebo effect.  For example, 25% of people with depression taking part in a well-designed trial of antidepressants experienced a significant improvement, compared with about 10% of people taking placebos.

The question of antidepressants either working, or not is at best not helpful and can be rather damaging.  In reality, some people find them very helpful, do not experience any significant side effects, take them for a while (often a few months), and then stop them again without any problems and remain well.

How do SSRIs work?

For those where SSRIs work well, they do not put extra serotonin into your system, but they allow the brain to more effectively use your existing serotonin levels.  Serotonin is a neurotransmitter which helps to pass electrical signals from one nerve cell to the next.  Is contained in a small balloon-like structure at the end of the nerve cell, and when required is released, travels along the gap from one nerve cell to the next, and then triggers a signal at the next one which then passes it on. 

However, that is not the end of the story, as the serotonin when it has done its job, is then recirculated.  It is reabsorbed by the nerve cell which released it in the first place, packaged back up again into the balloon and is ready to be released once more.  SSRI antidepressants block this reabsorption process to a degree.  So, once the serotonin is released it lingers around for longer, exerting a greater effect and so it effectively seems as if there are high levels of serotonin before eventually getting reabsorbed. 

One of the reasons why antidepressants are thought to take a while to have an overall impact on mood, is that the nerve cells do notice that there is not so much serotonin being reabsorbed and so readjust by starting to produce more than they would have ordinarily done in order to balance back the levels they are expecting again.  This process takes a while and does result in higher overall levels of serotonin eventually, but can take a few weeks to become noticeable.

What else causes depression?

Serotonin is clearly not the whole story, as a sizable proportion of people with depression do not improve significantly with antidepressants which boost serotonin levels.  Rather than therefore leading to a conclusion that "antidepressants do not work", a more meaningful question is to try and work out why some people improve and others do not.  This likely points to the issue that what we call "depression", can be quite a broad umbrella term encompassing lots of different people, varying situations, triggers, stresses and traumas which have led to a similar cluster of symptoms. 

We end up calling the result depression, but underneath this there may be a wide range of causes and reasons - only some of which are linked to low serotonin levels.  However for those people at least, having access to effective medication which assists them by boosting serotonin levels is valuable. Most psychiatrists and GPs, when surveyed, will readily acknowledge that a chemical imbalance is only one possible cause of depression.  In fact in one study they ranked this in last place amongst thirteen broader biological, psychological and social factors. This confirmed that most clinicians understand the complexity of a much wider overall concept of depression than just an imbalance of a single chemical such as serotonin.

What other neurochemicals may be involved?

Even if we put to one side the range of social and psychological factors which can quite easily lead to depression, and confine our thinking to biochemical imbalance alone, we know that there are a wide range of neurochemicals involved in depression. 

As well as serotonin others include histamine, melatonin, noradrenaline and dopamine to name a few.  In fact there are a range of antidepressants which work largely through these other mechanisms and have very little to do with serotonin at all.


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