Correlation does not equal causation – the depression and serotonin edition

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Alice Howarthhttps://dralice.blog/
Dr Alice Howarth is a research academic working in pharmacology and therapeutics at the University of Liverpool. She is vice president of the Merseyside Skeptics Society, has written for The Guardian, Breast Cancer Now and is co-host of the skeptical podcast Skeptics with a K. In August 2020 Alice took on the role of deputy editor for The Skeptic.

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If you can’t make your own brain chemicals – store bought is fine. So goes the well known saying which is well-intended to normalise taking antidepressants for those who live with depression.

I’ve often thought the phrase relatively harmless, even though as a depressed person who worked in clinical pharmacology I know it’s not quite as simple as all that. However, over the last few weeks we’ve seen how even these well-intended over-simplifications do contribute to harm. Don’t get me wrong, the bulk of the harm, as is often the case, was down to poor messaging and over-the-top media reporting. But the starting premise – that taking antidepressants is useful for people whose brains don’t make enough – was wrong, and contributed to that mixed messaging.

Let me explain with a story. I have depression and anxiety – I take antidepressants. I wasn’t born with depression. For me, it’s probably related to previously undiagnosed autism and specific experiences in my life that made things very challenging, although we may never know exactly what caused it. I’ve had periods of depression, anxiety and OCD on and off since I was six years old, when I first developed OCD. I’ve been on and off of antidepressants for the last six years.

When I first started taking antidepressants, my doctor explained that he could put me on the waiting list for therapy, but the waiting list was very long. In the meantime, he could put me on medication. He explained that the medication only works for just over half of people, but that the same is true for therapy. I waited well over a year (actually closer to two) to see a CBT therapist. The medication, I started the following week.

I won’t pretend that taking antidepressants is a “quick fix” – I am still depressed, and there are side effects for all medications, some of which for these pills have been difficult to bear. But I have worked with my doctors to find something suitable for me, and it helps.

We don’t really know exactly how antidepressants work. There are a bunch of different types that all do slightly different things. One category is called the selective serotonin reuptake inhibitors (SSRI); contrary to the idea that you are taking “store-bought” brain chemicals, these drugs  actually work by allowing your brain to continue making use of its own chemicals. Serotonin is released as nerves in the brain communicate with each other, and it passes between nerve cells – the reuptake inhibitor prevents that serotonin from being taken back up into the nerve cell where it is processed to be reused later (with a delay), and instead allows it to continue doing its job of helping nerve cells to communicate. We don’t think that SSRIs work because depression is caused by low serotonin, we simply know that increasing the availability of serotonin in the brain seems to help some people with depression.

We stumbled across the very first antidepressants by accident – the first of their kind, monoamine oxidase inhibitors (drugs that prevent the reuptake of neurotransmitters like serotonin) were originally developed to treat tuberculosis. But doctors realised that depressed patients who were treated for tuberculosis with these drugs, also started to find relief for their depression. Eventually researchers designed more specific drugs like SSRIs which had fewer detrimental side effects.

All of this is to say that while we don’t know how SSRI medications work, we do know that they do work, at least in moderate to severe cases of depression. Still, that didn’t stop a bunch of media reports over recent weeks claiming that a:

new review of existing studies found that depression is not likely to be caused by a chemical imbalance and said people should be made aware of other options for treating it.

With one of the authors of this review even going so far as to say that:

We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.

Now I’d like to tell you another story.

These days, I take an SSRI, but a few years ago I was taking a drug from another, similar class of drugs called SNRIs – they work in a similar way to SSRIs. For various reasons I (very unwisely) decided to come off the medication, cold turkey and without any medical support.

I was very, very unwell. I had severe withdrawal side effects, and I felt very poorly. Coming off this medication was the right choice for me, and I have since gone onto a different medication that I tolerate better. But the way I went about it could have been extremely dangerous. Suddenly coming off any antidepressant can be very dangerous, because as we do so it takes a little time for our brains to readjust to the sudden change and our brains are pretty damn important.

Many are, in my opinion, rightly worried that news reports lambasting the “serotonin theory of depression” run the risk of patients choosing to stop taking their medication without the medical support such a choice requires. I am not against anyone discontinuing a medication they no longer wish to take, but I am worried for patients who will do what I did and stop suddenly. I made a mistake, and I learnt the hard way that it was painful and dangerous to stop medication suddenly.

All this discussion on social media and in the news about serotonin and depression brings me back to the idea that “store bought is fine”. This is one of many reasons why understanding correlation and causation is crucial. We have convinced ourselves that low serotonin causes depression, because increasing serotonin levels in the brain helps treat it. But we just don’t have the evidence to support that.

On the other hand – yes, it might well be true that the cause of depression is not a chemical imbalance. But that does not mean that using SSRI based or other anti-depressants is not a useful treatment for depression.

As the wonderful Dean Burnett said by way of example – pain isn’t caused by a deficiency in paracetamol, but paracetamol can treat pain.

When we’ve spent years assuming that there is a causative relation between serotonin levels and depression then of course we will jump to “oh, no causation? Then the treatment mustn’t work”. This just isn’t true. Anti-depressants don’t help everyone, but we have plenty of data that shows that they do help some people.

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