The Case Against SSRIs: Rethinking The Narrative

A few weeks ago, I had coffee with a fellow colleague at work, a brief interlude from the tasks of the day.  She laughed nervously as she told me she would not be having any more boosters this winter, having had COVID-19 the week before (for the fifth time) and feeling “mostly fine” for it. It was not my place to critique her choice, it was her decision. It is her body after all, she has autonomy right? I have over the past couple of years aimed to remain neutral on individuals' choices on such a conundrum - wary of the possibility of a heated argument breaking out. It is controversial if you take such a stance. Not having “the vaccine”. This debate on whether we should or shouldn’t be having more COVID-19 vaccines appears not to have waned among medical professionals. The contentious issue follows everyone like a shadow with the rise and fall of COVID-19 cases. These discussions on the COVID-19 vaccine, where you are constantly treading on egg-shells, have made me ponder bigger questions. To what extent do we have a choice in taking a drug or not? Are we subliminally pressured to do so by society? Or worse, are we being pushed to do so by drug companies profiteering under a guise to protect us?

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Recently, a great deal of media coverage has been given to the topic of SSRIs, or selective serotonin reuptake inhibitors. These drugs are most commonly used to treat symptoms of major depressive disorder, and related psychiatric conditions. They are said to work on the basis of increasing “deficient serotonin” that many researchers regard as the cause of depression (Chu and Wadhwa, 2022). Serotonin is a neurotransmitter, meaning that it’s used by the brain to coordinate electrophysiological signalling between various regions. The mental processes modulated by serotonin include mood, perception, anger, and memory - to only name a few (Berger et al, 2009). SSRIs temporarily inhibit the reuptake of serotonin by synapses, which are gaps between individual brain cells; this means that serotonin can float around between neurons for longer. As a result, serotonergic activity increases. If we suppose that depression is caused by a deficit in this type of activity, then it would be sensible to assume that increasing the length of time that serotonin “floats around” in the brain might result in a lessening of those symptoms. Sounds pretty great, right? Your brain is deficient in a certain chemical and, as the story goes, a drug will fix the problem. However, things are never really this simple, in the same way that depression isn’t a simple disorder. But the serotonin narrative, as we shall see, is a very profitable one — which is perhaps why many of us are convinced that SSRIs are an effective way of treating depression.

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There have been various commentators on the issue. Ben Goldacre, in his book Bad Pharma, highlighted some of the theoretical, ethical, and practical problems with asserting a causal link between low serotonin and depression (Goldacre, 2013 p. 258). One of the major issues with this view, according to Goldacre, is that it has been deeply embedded into societal thought, to the point where it has become normative (Goldacre, 2013). Various forms of incentivised messaging have pushed us to think that if someone is depressed, they should consider taking medication.  Despite this pervasive view, the “serotonin hypothesis” is not as well-supported by scientific evidence as we’re led to believe. This becomes more apparent when Goldacre discusses the drug Tianeptine, which was labelled as a selective serotonin reuptake enhancer. Thus, it should reduce serotonin levels, (doing the opposite of what SSRIs accomplish), and increase depressive symptoms, though research has revealed it is also a beneficial treatment for depression. (Goldacre, 2013). We have a situation where serotonin inhibitors and enhancers can apparently both treat depression. This raises a lot of questions about the real and reliable role of serotonin in generating depressive symptoms. Interestingly, researchers do not think Tianeptine can be labelled as an SSRE anymore, due to its lack of long term effect on the serotonin pathway. Despite this, it is still found to be useful in treating depression (McEwen, 2010) This type of information is clear as mud, it is yet another thing that requires more research. In the case of Tianeptine, that is another story - yet another rabbit hole. Why then are SSRIs still commonly sold as the answer to treating depression if there are so many conflicting messages of what “does” and “doesn't” work?

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Goldacre attributes widespread SSRI use for depression due to the influence of powerful marketing techniques (Goldacre, p. 259). The serotonin hypothesis, he argues, did not just emerge out of thin air. It has been carefully nurtured by industry leaders to ensure that it remains the status quo. One such example is from an advert for paroxetine (an SSRI) by GlaxoSmithKline. GSK is the 10th largest pharmaceutical company in the world (Fortune, 2022). The advert states: “If you’ve experienced some symptoms of depression nearly every day, for at least two weeks, a chemical imbalance could be to blame” (Petersen, 2009, p. 102). There are a multitude of other examples like this, and it almost always goes the same way: a reassuring voice narrates scenes of happy families, people engaging in hobbies, and beautiful landscapes. It could all be yours, if only you addressed the chemical demons in your brain. Recently, however, a new meta-analysis of research concerning the role of serotonin in depression has challenged this starry-eyed view.

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The paper that hit the headlines was by Professor Joanna Moncrieff and colleagues at UCL stating “Analysis: Depression is probably not caused by a chemical imbalance in the brain - new study” (Moncrieff and Horowitz, 2022). On conducting an extensive review of the current relevant research out there, the researchers came to several conclusions. Notably, they found that SSRIs are “barely distinguishable” from taking a placebo drug when treating depression and that antidepressants seem to have a generalised emotional numbing effect. The authors, furthermore, point out that they are not sure about the biological mechanisms that cause this numbing effect, but that we should also be sceptical about serotonin as a mechanism for depression. In one particular study they reviewed, participants’ levels of serotonin were artificially lowered, and this did not result in depression. Several other studies were also examined, and they came to the conclusion that any claims to a robust link between low serotonin and depression cannot be backed up by scientific evidence. The paper is essentially a vast review of summaries already out there on SSRIs, serotonin and depression. Has such a sweeping analysis of the research out there put the serotonin hypothesis theory to bed?

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Not exactly. The serotonin hypothesis is still highly influential and deeply ingrained in societal thought. (Moncrieff et al. 2022). One example of this can be found in a statement from the Head of Psychiatry at the University of Melbourne, Professor Christopher Davey. In response to Moncrieff and his colleagues at UCL, Davey argues we are not sure how antidepressants really work due to the complexity of the brain and that medicine is “pragmatic”. He compares this conundrum to how we do not fully understand how general anaesthesia works (Davey, 2022). But that is beside the point. General anaesthesia is very much a means to an end, whereas antidepressants are more a cog in the wheel of potentially aiding or overcoming depression. Davey concludes that people with depression deserve “better treatments”. Somehow, continuing to blindly prescribe SSRIs, with no real idea how they really work, does not help people in the grand scheme of things. One of the potential key criticisms of Moncrieff and his colleagues' paper surrounding this debunking of the serotonin hypothesis, however, could be that they only analysed  one  subtype of serotonin receptor (5HT1A) despite fourteen having been identified (Moncrieff et al). The other 5HT receptors and their link to depression have not been well-characterised. Bearing this in mind, there is more research to be done in the relationship between serotonin and depression. Still, antidepressant prescriptions in the UK are rising, having nearly doubled in the past decade (Heald et al, 2020). But without researching and offering other therapies, which may be more efficacious, creating a medical system that relies so heavily on SSRIs may do more harm than good.

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Why should we solely expect an SSRI to lead people down the right path, just because there is some tenuous evidence out there that certain people feel benefits from taking them? (Davey, 2022). The brain is deeply complex, and it would be foolish to reduce its functionality – which depends so heavily on environmental context – to one specific biological pathway. However, many leading professionals still hold belief that depression can be attributed to faulty chemistry alone, despite mounting evidence to the contrary (Moncrieff et al, 2022). The arrow of causality goes both ways; the environment affects brain functioning, which in turn affects how a person interacts with the environment. Targeting one chemical pathway neglects a whole universe of other factors that may be involved. It is harmful and dangerous to send out such a message, and it is more likely to result in patients believing they cannot, through their own efforts and lifestyle changes, overcome depression. This type of messaging is also more likely to result in patients being hesitant in ever discontinuing SSRIs, leading to “lifelong dependence” (Moncrieff, 2022). Bearing drug companies in mind, the only person that is going to truly care about evaluating patient SSRI use and discontinuation is the patient themselves in having a conversation with their doctor. But the first step is changing the messages that are sent out to patients surrounding depression. They will not ever consider stopping or gradually reducing their SSRI dose if they believe their depression is caused by chemical abnormalities in their brain. They will instead potentially believe something along the lines of: “that’s just how I am” and “only this drug can regulate me”.  Strict biological determinism, turned into a pervasive societal dogma, can make us feel disempowered in the face of sincere challenges.

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There could be a plethora of reasons as to why someone might be suffering with depression. Poverty, harmful relationships, work stress, grief, and an unhealthy lifestyle have all been linked to the development of depressive disorders. It is not simply because a person is lacking a certain amount of a chemical in their brain – chemical imbalances do not arise out of thin air. It is perhaps only now that people are starting to be alerted to the SSRI conundrum and its potential harms to individuals and society. Drug companies, however, will be disinclined to draw attention to this narrative, because it hurts their profit margins.

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Before you come at me with your burning torches, I am not pointing the finger or shaming anyone who takes SSRIs. I think it is important, in light of the UCL paper, to really underline and present the side of SSRIs that certain people want swept under the carpet. The advantages and disadvantages of taking a drug should be laid bare for all to see, but they just aren’t as it's often a question of money and profits. That is why you have to often do your own digging - valuable detective work for the sake of your own health. We need to talk about Serotonin, and we need to trust evidence above all else.

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With thanks to Natalia Zdorovtsova for her advice and guidance on all things antidepressant and neuroscience.

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References:

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Berger M, Gray A J, Roth L B. 2009. The Expanded Biology of Serotonin, National Library of Medicine, National Center for Biotechnology Information, [online]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864293/(Accessed 23 August 2022)

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Chu A, Wadhwa R. 2022. Selective Serotonin Reuptake Inhibitors. [Updated 2022 May 8]. In: National Library of Medicine, National Center for Biotechnology Information, StatPearls [online]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK554406/ (Accessed 22 August 2022)

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Davey, C. (August 2022) The Chemical imbalance theory of depression is dead – but that doesn’t mean antidepressants don’t work, The Guardian [online]. Available at: https://www.theguardian.com/commentisfree/2022/aug/03/the-chemical-imbalance-theory-of-depression-is-dead-but-that-doesnt-mean-antidepressants-dont-work (Accessed 25 August 2022)

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Goldacre, B. (2013). Bad Pharma: How medicine is broken, and how we can fix it. London: HarperCollins Publishers.

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Global 500. Fortune. Available at: https://fortune.com/global500/2022/search/?fg500_industry=Pharmaceuticals (Accessed 23 August 2022) 

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Heald, H. A, Stedman M, Davies M, Livingston M, Taylor D, Gadsby R, (2020) Antidepressant Prescribing in England: Patterns and Costs, The Journal of Clinical Psychiatry: The Primary Care Companion for CNS Disorders. Available at: https://www.psychiatrist.com/pcc/depression/antidepressant-prescribing-in-england/ (Accessed 5 September 2022)

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Karanges, E. and McGregor S. I, (2011) Antidepressants and adolescent brain development, Future Neurology, vol 6, 6, [online]. Available at: https://www.futuremedicine.com/doi/abs/10.2217/fnl.11.51 (Accessed 25 August 2022)

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McEwen, B. S, Chattarji, S, Diamond, D. M, Jay, T. M., Reagan, L. P, Svenningsson, P, Fuchs, E., (2010) The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation, Molecular Psychiatry, 15 (3): 237-249  [online]. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902200/ (Accessed 25 August 2022)

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Moncrieff, J., Cooper, E. R, Stockmann T, Amendola S, Hengartner P. M, Horowitz A. M,  (2022) The Serotonin theory of depression: a systematic umbrella review of the evidence, Molecular Psychiatry, [online]. Available at: https://www.nature.com/articles/s41380-022-01661-0 (Accessed 29 August 2022)

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Moncrieff, J. and Horowitz, M. (2022) Analysis: Depression is probably not caused by a chemical imbalance in the brain – new study. The Conversation. [online]. Available at: https://theconversation.com/depression-is-probably-not-caused-by-a-chemical-imbalance-in-the-brain-new-study-186672 (Accessed 26 August 2022)

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Petersen, M. (2009). Our Daily Meds: How the Pharmaceutical Companies Transformed Themselves into Slick Marketing Machines and Hooked the Nation on Prescription Drugs; Picador

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Further Readings

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Ahsan, S., (2022) I’m a psychologist – and I believe we’ve been told devastating lies about mental health, Mental Health Opinion in The Guardian [online]. Available at: https://www.theguardian.com/commentisfree/2022/sep/06/psychologist-devastating-lies-mental-health-problems-politics

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Goldacre, B., (2014) I Think You’ll Find It’s a Bit More Complicated Than That, London: Fourth Estate

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Hari, J., (2019) Lost Connections: Uncovering The Real Causes of Depression-And The Unexpected Solutions, London: Bloomsbury Publishing