No evidence to link low serotonin & depression

A new meta-analysis has seemingly debunked the chemical theory linking depression and low serotonin levels. It shows that there is ‘no convincing evidence’ that the two are somehow linked.

Common conventional wisdom states that depression is caused in part by a chemical imbalance with low serotonin activity or concentrations. Many healthcare professionals tout this theory and use it to inform treatment plans they put into place for their patients.

Psychiatric textbooks still give the lowered serotonin theory widespread attention as a key cause of clinical depression. In fact, in a statement published in 2019, the Royal College of Psychiatrists claimed that:

The original idea that antidepressants ‘correct a chemical imbalance in the brain’ is an oversimplification. However, they do have early physiological effects and effects on some aspects of psychological function.

However, despite the chemical theory’s prevalence in modern psychiatric and mental health treatment, a new study, published recently in Molecular Psychiatry, found no link at all between depression and low serotonin levels.

According to the study, there is no support at all for the chemical theory’s core hypothesis; in part as a result of this, authors also question the high prescription rates of common antidepressants.

Many clinicians agree the idea that a simple chemical imbalance causes depression is pretty archaic. However, many still support antidepressant use as an option for patients when paired with other treatment forms. These other forms can include talking therapy, cognitive behavioural therapy (CBT) and the like.

Depression and low serotonin

There is little to no convincing evidence linking depression to low serotonin activity or concentrations. It is always difficult to prove a negative. However, the study’s lead author, Professor Joanna Moncrieff of University College London, says that:

‘I think we can safely say that after a vast amount of research conducted over several decades there is no convincing evidence that depression is caused by serotonin abnormalities, particularly by lower levels or reduced activity of serotonin’

The study was a review of existing overviews of research on serotonin and depression. This included detailed meta-analyses and systemic reviews. The study’s authors compared serotonin levels, alongside its breakdown products, in the blood and brain fluids. Those diagnosed with depression were no different than the control participants.

Multiple studies on serotonin receptors and the serotonin transporter have shown that depression might even be associated with higher levels of serotonin activity. However, the evidence for this theory is inconsistent and weak. These heightened levels are possibly due to antidepressant use by those being treated for depression.

Depression and artificially lowered serotonin

The study also found that artificially lowering serotonin levels does not cause depression and associated symptoms. Studies have used this technique – depriving healthy participants’ diets of the amino acid required to make serotonin – to look at the link between low levels and mood.

However, researchers concluded that depleting serotonin reserves in this way did not cause the onset of depression. A minority of participants with a history of depression in their families have been shown to suffer with depression on this diet. However, the evidence is weak overall. More recent tests have proven far less conclusive. Additionally, the most reliable data is from a very small participant study.

Depression and serotonin in a fatalistic setting

However, the popular myth endures – many members of the public believe that low serotonin or similar chemical imbalances underly depression.

This can be problematic for several reasons. In particular, it is quite a pessimistic view. Many people suffering from depression think that depression is inherent to them. They believe that a chemical imbalance within their body that is outside of their control causes their depression.

Long-term medical intervention – chemical intervention – is the only viable treatment in this scenario. They are led to believe that antidepressants serve to target and rebalance these hypothetical serotonin imbalances.

In this, Professor Moncrief says, they believe that antidepressants work in the same way as insulin for diabetes [which] is completely misleading. We actually don’t really know what common antidepressants are doing to the brain.

The results of this research can be potentially world-altering for those suffering from depression.

What does this mean for antidepressants?

As above, there is still widespread support for antidepressant use, though this may change with time.

For the moment, though, the Royal College of Psychiatrists stands by that antidepressants can alleviate and improve depressive symptoms. The drugs bring about alterations in key areas of brain function. For example, animal studies have shown that antidepressants increase the number of brain cells, improve their function, and bolster connectivity between them. This means improved processing of emotional information even within just a few hours of taking antidepressants.

The Royal College of Psychiatrists say:

Antidepressants are an effective, NICE recommended treatment for depression that can also be prescribed for a range of physical and mental health conditions. Treatment options such as medication and talking therapy play an important role in helping many people with depression and can significantly improve people’s lives. Antidepressants will vary in effectiveness for different people, and the reasons for this are complex, which is why it’s important that patient care is based on each individual’s needs and reviewed regularly.

We would not recommend that anyone stops taking their antidepressants based on this review and encourage anyone with concerns about their medication to contact their GP.

This is incredibly important. If you are taking antidepressants, do not stop based on this new study. If you have any concerns over your antidepressant use and would like to come off of them, consult with your healthcare provider. Do so at their suggestion and under their observation.

NICE recently published its first set of guidelines in over a decade for treating adult depression. These guidelines recommend a range of different, evidence-based treatments. These included antidepressant use in conjunction with various forms of psychological therapies.

Psychiatrists’ views on antidepressants, depression and serotonin

Very few psychiatrists follow the simple chemical imbalance theory. So says Allan Young, a research leader in the Institute of Psychiatry, Psychology, and Neuroscience, at King’s College London. Rather, they largely follow the biopsychosocial model.

According to Young, the use of antidepressants is based on strong clinical trial evidence. This proves their efficacy and informs their medical use. The recent review doesn’t alter this.

Phil Cowen, professor of psychopharmacology at the University of Oxford, notes that ‘no mental health professional would currently endorse the view that a complex heterogeneous condition like depression stems from a deficiency in a single neurotransmitter.’

For Cowen, the recent review leaves a lot of scope for interpretation. What the study omits is as revealing as what it includes. He cites a meta-analysis published in Molecular Psychiatry in 2021 that the recent review didn't include. This meta-analysis showed that changes in the peripheral blood were associated with major depressive disorder, particularly decreased L-tryptophan.

In fact, his own research points to tryptophan depletion playing a role in depressive symptoms in some remitted depressed patients.

He concludes that serotonin’s role in depression – or lack thereof – is an entirely separate question from the efficacy of selective serotonin reuptake inhibitors (common antidepressants). The view that antidepressant drugs could work only by correcting a chemical imbalance is odd to him. He states that ‘no current theory of antidepressant action … makes this assertion.’

The future of treatment for depression

However, this new research weakens the link between chemical fixes for depression. It highlights a well-established yet growing trend in modern psychiatric practice – a shift towards thought-based and behavioural therapy.

Therapies such as CBT, DBT, psychotherapy, EFT, and certain recovery programs such as 12 Step and SMART Recovery, which both addresses though, past behaviours and feelings, and current actions and behaviours, are incredibly beneficial.

In fact, there is a strong argument to suggest that they are more beneficial to those going through addiction recovery than antidepressants – or, at least, than antidepressants on their own. Antidepressants have their place, as we have seen, but behavioural and thought-based models of treatment need to go hand in hand with them.

This is especially true for those who suffer from any of the diverse side effects associated with both short- and long-term antidepressant use, particularly selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs).

Side effects of SSRI & SNRI antidepressants can include:

• Shakiness
• Agitation
• Dizziness
• Nausea and sickness
• Indigestion and digestive problems
• Loss of appetite, insomnia
• Fatigue and drowsiness
• Headaches
• Sexual dysfunction
• Changes in weight

Side effects of tricyclic antidepressants (TCAs) include:

• Heart rhythm concerns
• Dry mouth
• Blurred vision
• Constipation
• Trouble passing urine
• Fatigue & drowsiness
• Dizziness
• Weight gain
• Excessive sweating

Furthermore, on starting a course of antidepressants a person can experience suicidal ideation. This can have devastating effects on a person who is already at the end of their tether and has already been contemplating suicide.

Depression and serotonin: Where to go from here?

All of this points us to a couple of natural conclusions.

Firstly, as depression and serotonin levels don’t have a causal relationship, and as the chemical imbalance theory is now being put to bed, depression is far less deterministic than we once thought. In simple terms, you aren’t destined to suffer from depression forever if you happen to suffer from it once or twice.

However, some people are more predisposed to depression than others, particularly if there is a history of depression in their family.

Secondly, we can see that there is still a lot of evidence supporting continued antidepressant use. As we have seen, expert opinion has reached a consensus around this – the clinical data supports ongoing use, despite side effects and despite the unpinning of depression and serotonin levels.

Thirdly, however, depression doesn’t follow the ironclad chemical imbalance theory that we once thought it did. Though many psychiatrists have dismissed this theory over the years, the popular and widespread clinical belief still held to it. In undermining the chemical imbalance theory to the point at which we can now confidently retire it, the way is clear for other treatments to come to the foreground.

These include the thought-based and behavioural therapies mentioned above (such as CBT, DBT, psychotherapy, EFT, and certain recovery programs such as 12 Step and SMART Recovery). Antidepressants are a good tool in the fight against depression. However, they are only one tool. Thought-based and behavioural therapies need to play a far more active role in the long-term treatment of depression in most cases.

This especially pertains to addiction recovery. Here, thought-based and behavioural therapies are particularly beneficial.

The role of holistic therapies in treating addiction

At Recoverlution, we advocate a number of evidence-based thought therapies and holistic therapies to help you along in your journey of recovery. We also believe that connection with like-minded others is a crucial part of sustaining recovery from addiction.

Whether you are here to find out more about addiction, connect with others in recovery, run your own support meetings or improve your own well-being, we provide everything you need at your fingertips.

Read more:

8 habits to improve your mental health in addiction recovery

References:

• No Evidence Low Serotonin Causes Depression?https://www.medscape.com/viewarticle/977753
• Side effects - Antidepressants -https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/antidepressants/side-effects/