Ian Cleary

Depression – Beyond the myth of a Chemical Imbalance

September 8, 2015IanDepression, anxiety and other conditions, NeuroplasticityComments Off on Depression – Beyond the myth of a Chemical Imbalance

Beyond the myth of “Chemical Imbalance”


Many of the people I see with chronic illness will also suffer from depression. Some come to me with depression as their primary issue while others develop depression as a consequence of having another illness like chronic pain, anxiety or debilitating fatigue.

A critical step in making change is to understand the problem. One of the big obstacles that can get in the way of making meaningful changes with depression is the outdated belief that depression is caused by a chemical imbalance.

I hear references to a “chemical imbalance” so often that it is clear that this outdated theory is still entrenched and lingering in the public consciousness.

So this is an update on some more modern understandings of depression. Like many things, the understanding of how our mind and body are inseparately connected and influencing each other combined with the knowledge that our brain changes and adapts with all experience (Neuroplasticity) has cast a fresh light on depression, and useful paths of recovery.


Depression has been around forever, however the theory as to what causes it and therefore the treatments have changed. Early on it was seen in very religious terms as a form of possession of demons or spirits. Later Hippocrates thought it was to do with imbalances of four bodily fluids with depression caused by too much black bile so blood letting was practiced. We moved through ideas about fluid imbalances to emotional imbalances – repressed inner anger then onto thinking styles and lack of coping skills. The treatments have varied as the theories changed and have included exorcism, cold baths, diet changes, exercise, psychotherapy to Benjamin Franklin’s ‘electricity to the brain’ concepts.

Since the 1950’s however a shiny new theory arose. It suggested depression was the result of a simple chemical imbalance in the brain. The chemical imbalance theory was put forward because giving depressed people certain chemicals showed some effectiveness. It came about by luck when people on a particular drug for Tuberculosis saw improvements in their depression. It was not a drug designed in the lab to specifically target depression.

However it is important to understand that the theory didn’t come about by actually finding a chemical imbalance but merely finding that certain drugs created change in the depressed state for some people. It was a neat theory based on the idea that if you gave someone a chemical that helped, they must therefore be deficient in that chemical. The theory was refined to be a lack of a specific chemical called serotonin – a neurotransmitter with many functions.

If people got better while on these medications and then stopped taking them the relapse rate was very high. This further strengthened the chemical imbalance theory.  There seemed to be a genetic link as well. So the chemical imbalance theory was looking good and the implications had people on medication for the rest of their life to counter a purely biological issue.

There were also many drug trials that showed effectiveness of these drugs. So this theory went from a possible theory to being generally accepted by the medical world and the general public.  Prozac went on to be the star of the show and the most prescribed medicine in the United States in the 1980.

This theory did a number of things. Firstly it made depression instantly a purely medical issue for the GP’s clinic. It also helped remove the stigma of depression as it removed any sense of blame. It was after all an inherited chemical imbalance. However the downside was that it also created a powerlessness or passiveness. There was an implication that people were at the mercy of their biology and so medication made sense as the only useful option. And if the first drug didn’t work, which it often didn’t, then your options were to keep swapping through the variety of drugs until you found ‘the one’.  The other clear downside of this theory was that if the drugs didn’t work then you had ‘treatment resistant depression’- and there wasn’t anything else you could do.



There were however some major issues with the chemical imbalance theory which would eventually lead to its demise.

The rapid global rise – Firstly the rapid rise of depression in the population doesn’t fit with the chemical imbalance theory.

Better technology – Brain science and technology have improved and no evidence has been found that people with depression actually have reduced serotonin levels.

Testing – If you give a healthy person a drug that limits the availability of serotonin, the theory would suggest that these drugs would trigger depression. They don’t. And here is the really weird thing. If you give a depressed person a drug that actually lowers available serotonin in the brain (the opposite action of the anti-depressants) those drugs are still as effective in helping treat depression.

Also other families of anti-depressants that act on the action of different neurotransmitters worked equally effectively and lastly the time it took to see results (a few weeks) biologically didn’t match theory.

So it went from a nice theory to a shaky one. BUT the tests did show anti-depressants were really effective for depression. Didn’t they?



The lack of evidence for a chemical imbalance encouraged people to go back to the test results for a closer look.

Firstly the data on anti-depressants never suggested that the majority of people see results. It’s more like a third but that’s better than doing nothing. However it is also known that giving people a placebo pill also gets pretty good results. So, given the possible side effects of these drugs, they need to be significantly better than the placebo result.

Getting information, other than published data, from Pharmaceutical companies is rarely possible and getting it from the FDA is not straight forward. However under the Freedom of Information Act, data on a large number of published placebo-controlled trials and non-published trials for Anti-depressants were collated and re-analysed.

On further scrutiny this was the finding –

Anti-depressants performed no better than placebo in all but severe depression. Even then the results were statically significant but not clinically significant. Meaning that while the drugs were marginally better than placebo in trials for severe depression, in the real world the difference was not really relevant.

As an aside, the drugs companies were shown to have been misleading in what they published and what they didn’t publish. In the field this is called ‘Publication Bias’ but others aren’t as kind and call it fudging the results. An interesting read on this can be found in The Emporers New Drug by Irving Kirsch or a more general understanding on how test results can be tweeked for purpose – Bad Science by Ben Goldacre.

So why prescribe them at all? Because they DO work……for some people some times.  Depression can have a devastating impact on people’s lives so any success is important. These drugs can work spectacularly well for some people. The data suggest that it is not a large number of people though, around 30%, which it turns out is about the same as the placebo results. Certainly not the majority.

So in the push to have a single pill solution for depression there are therefore many people (literally millions) who see no results with medication and are left moving through the drug options in the hope that one will eventually work. If they have bought into the ‘chemical imbalance’ theory they can be left feeling pretty hopeless with ‘treatment resistant depression’ and out of options when in reality they are the norm.

So the obvious next question is – are there other options?

A rethink of depression

One of the problems with a diagnosis of depression is that it doesn’t give any insight into the underlying driving problem – it’s a description of what the person is experiencing not the reason behind it. That is a failing of mental health in general – a diagnosis is often based on a description of symptoms not causes. Vomitting for example is not a diagnosis but a description. It would be odd if we didn’t look any deeper and offered remedies based on the vomiting alone. We need to know why this person is vomiting.

So a rethink of depression has us seeing it as a symptom (or collection of symptoms). It is a sign that something is wrong. Like pain or fever it only tells us there is a problem but not what the problem is. People are unique. So for good health, knowing about the person, their unique circumstance, allows for more appropriate treatment than a single pill.

Stuck in a normal healthy state

It is now recognised that most people will experience the depressive state at times in their lives. Healthy individuals move along a continuum of states through out their lives depending on their life experience. So this understanding allows us to see that depression is not some pathological ‘brokenness’. A new way of seeing the problem of depression is about the ease that someone falls into the depressed state and the inability to get out of that state.

Perhaps, like pain, we need to think of it in terms of acute versus chronic states. Acute pain is an appropriate response to tissue damage. However chronic pain is very different. Pain has become an inappropriate response occurring after the tissues have healed.

Some are now seeing the depressed state as a normal/natural and healthy immune response. When we have an infection or inflammation we go to bed, reduce activity, our mood changes, effecting our emotions and appetite drops while our body heals. This actually sees ‘acute depression’ as a useful response of the nervous and immune system.

But it is clearly important to move into this state appropriately and of course move out of it appropriately. Staying in the state for extended periods becomes problematic when you understand the nature of NEUROPLASTICITY.

Due to the nature of neuralplasticity, and the constantly adapting and dynamic brain brain, ongoing activation of this state can create changes in the brain – altering our physiology and psychology – and we move from an acute depressed state to a stuck chronic state. It’s no longer an appropriate response and creates changes in the body and in the brain.

People clearly move into a depressed state for many reasons and this can be influenced by emotional issues, illness, stress, thinking styles, genetics, medications, diet, lack of exercise, poor sleep, trauma or a combination. These can all influence a depressed state and so understanding these can help direct a personalised recovery strategy from the depressed state.

A personalized long term approach will also importantly focus not just on getting out of the depressed state but also look at avoiding moving into the depressed state in the future. (relapse).

A useful question to ask might be – what is going on that has triggered this depressed state and what changes can be made to assist in getting out and staying out. This allows people to explore the many drug and non-drug approaches without being burdened by the feeling of being biologically ‘broken’ with a chemical imbalance.

 A Personalised treatment plan

For those who have found that medication is not working, it can be useful to understand that this does not mean that things are hopeless. Drug trails show these people are in very good company. There are many, many things that people in this situation can still benefit from. It may require people to see depression from a perspective broader than just a single missing neurotransmitter but this instantly opens up possibilities such as looking at stress, behaviours, beliefs, thoughts, exercise, diet, social contacts and relationships and emotions.

The drugs we are using now for depression haven’t changed that much in 60 years and clearly are not the single magic bullet we were hoping for. Tellingly, the pharmaceutical industry are withdrawing from research into this field. So while these drugs will continue to play an important role as part of the solution, attention is shifting to a more personalised treatment. Tailoring treatment to each individual instantly increases the possible options available.

The Chemical Imbalance theory reduced options. Leaving it behind to see depression as a general indicator that something isn’t right and needs attention can be a really productive and useful way of finding solutions. Beyond the myth of chemical imbalance are many options.

Things are never hopeless when there are other options. 


Further reading on the myth of depression can be found here.

SCIENTIFIC AMERICAN  – Antidepressants – Do they work or don’t they? 

HUFFINGTON POST – The Emperor’s New Drug 



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