Mind Matters with Kyle MacDonald: Antidepressants work for depression but not in the way that we thought

Don't stop taking your medication, because it does work. Photo / 123rf

ADVICE

Q: Is it true that serotonin doesn't cause depression? Does that mean my antidepressants don't work? I've always been told that depression was a "brain disease".

A: It is true that a recent wide-ranging review of the available literature to date by researchers at the University College London has shown that the evidence for a clear link between serotonin hypotheses of depression is weak at best, non-existent at worst. The study, published in the Journal of Molecular Psychiatry and titled The serotonin theory of depression: a systematic umbrella review of the evidence, made headlines around the world - perhaps a sad statement about how topical depression is right now.

However, this is not news to clinicians, and doesn't say anything about whether or not your antidepressants "work". It might, however, say something about how they work.

The idea that depression is simply a "disease of the brain" and therefore caused by a lack of serotonin has always been questionably reductionistic and understood to only ever be a part of the story by people working in the field.

It has, however, been a view that has persisted over the years, and in part justified by the relative success of the modern antidepressants - the SSRIs or selective serotonin reuptake inhibitors. These are your Prozac, Aropax and Citalopram for instance.

All of these drugs are hypothesised to work by increasing the levels of serotonin in the brain and, hey presto, no more depression.

What's not in dispute is that these medications work, they've been subjected to a ton of research, and many years of clinical use have demonstrated their effectiveness - so if you take nothing else from this recent bunch of headlines, please hear this - don't stop taking your medication and if you have any concerns speak to your GP.

You might now be wondering how can it be true that the "serotonin hypothesis" is wrong, and that these antidepressant medications still work.

Well, the first part is easy. Despite it having persevered for so long it was always obvious that depression could never be as simple as a brain that just didn't produce enough serotonin. Much of therapy is about understanding the why, and with people who turn up in front of you, there is always a way of making sense of how they find themselves experiencing depression.

It is almost always adverse childhood experiences, and/or adverse events in adulthood. It may very well be the case that some underlying temperamental mechanisms predict how exactly people respond to adverse events and trauma - because not everyone responds with depression. But it has never made sense to me that it is simply a chemical imbalance - like diabetes of the brain.

I do also get that for some it can be a reassuring idea though, especially if it comes with medical intervention, and means not having to think too deeply about what ails them. As an idea, it appeals to human nature and the desire for a simple, pain-free, cure.

Back to that cure. We know the medications work, so the logical conclusion is that they work - but not in the way that we thought. And this is where I think it gets quite fascinating.

One of the leading contenders for how these medications may work - if not by fixing your serotonin levels - is that they increase, through a series of chemical mechanisms, what we call "neuroplasticity". That is the brain's capacity to change and rewire itself. Simply put how quickly we learn and change at a neurological level.

Subjectively, depression feels like getting stuck, and recovery from depression usually involves learning and implementing new behaviours, new thinking habits and new ways of seeing relationships and the world. Personally, I love the idea that perhaps antidepressants don't passively fix a broken brain but instead help us to get active and reprogram our own brains.