State of Mind

Why Has the Misleading “Chemical Imbalance” Theory of Mental Illness Persisted for So Long?

Two brains on uneven golden scales.
Photo illustration by Slate. Photos by Bet_Noire/iStock/Getty Images Plus and SciePro/iStock/Getty Images Plus.

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Recently, one of my friends messaged frantically, asking if I had seen the big serotonin study that had been published by scientists at University College London. The study, an umbrella review critically evaluating pre-existing research, concluded that there was little support for the idea that depression was related to abnormally low levels of serotonin. As a philosopher of medicine and psychiatry, I had to confess that I had seen the study and was utterly unsurprised at the results. It’s true that the authors of the study are controversial figures, vocal to sometimes vituperative critics of the mental health status quo, leaving heated debates in their wake with each new publication. But the authors’ conclusion has been an open secret within mental health circles for at least a decade. The very public dispelling of this “serotonin model” has also removed a key plank in the widely believed but oversimplified myth of mental illness being caused by a “chemical imbalance.” My friend was devastated.

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The chemical imbalance myth has its roots in the late ’70s and ’80s when psychiatry was dominated by the desire to understand mental illness in primarily biological terms—as deviations in brain structure, neurochemistry, and genetics. When the first generation of selective serotonin reuptake inhibitors (or SSRI) antidepressants such as Prozac was introduced in the late ’70s, a key part of their marketing claimed that they targeted specific neurochemical imbalances.

Psychiatry is now interested in a wider range of factors contributing to mental illness—including genetics, gut microbiome, environmental influences, socioeconomic factors, and interpersonal stressors—and the marketing of psychiatric drugs is more tightly regulated. However, as the authors of the new study point out, this initial starting point has already crept into everything from public health messaging to popular websites. For instance, though the American Psychological Association takes no stance on the serotonin model when describing SSRIs, Australia’s Department of Health, describes antidepressants in terms of the chemical imbalance model.

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In the past year, 8.3 million people in the U.K. (about 12 percent of the population) took antidepressants. The most recent figures from the United States, collected between April and May by the National Center for Health Statistics, show that approximately 23 percent of adults took prescription medication for their mental health. The vast majority of these prescriptions, including the one taken by my friend, are for SSRIs. And it’s no surprise that many people who have been prescribed an SSRI believe that they work by increasing the availability of serotonin, thereby correcting the abnormally low levels of serotonin responsible for her depression. Finding out that this story of how SSRIs work was unsubstantiated made her question whether she should be taking them in the first place.

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This is a common reaction. As I write this, my social media channels are full of patients who say they now want to stop taking SSRIs. The response by concerned mental health professionals and skeptical commentators has been twofold: First, they are poking holes in the study—usually an important part of scientific method. But in this case I suspect it is sort of pointless, given that many experts already thought the serotonin model to be a nonstarter, and this is a review of existing work rather than new research. Second, they are correctly noting that though we are unsure how SSRIs and other psychiatric drugs work, we have reason to believe that they do—an important distinction.

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Medical treatments, including psychiatric drugs, are primarily tested for efficacy, usually via randomized controlled trials rather than more primary research into how or why they work. In many ways, this makes sense: When there is a problem, especially with one’s health, the priority is fixing the problem rather than working out why this particular fix works. Indeed, there are many common medicines and treatments where we are not entirely sure how they work, despite being fairly certain that they do—including acetaminophen (or, as we call it in the U.K., paracetamol).

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There are many people who swear SSRIs have improved their lives, and pooled reviews and meta-analyses point toward their efficacy. Based on such reviews,  they are recommended treatments for depression (and a host of other mental illnesses) via the U.K.’s National Health Service and the American Psychological Association. On the other side, critics point to a number of deep issues with this research such as the failure to publish negative results, the fact that trials tend to be funded by pharmaceutical companies, and the exclusion of severely depressed patients from the trials. And then there is the perennial problem of taking experimental results about a broader population or group and applying them to a particular individual. I am inclined to think the debate over the efficacy has distracted from the main point of the study—in the case of mental health, how and whether something works both matter.

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In many ways my friend and I are very similar: prone to severe depression, from the same ethnic background, of similar ages, both philosophers. We have both spent the vast majority of our adult lives in precarious environments that incentivized a certain kind of relentless pursuit of achievements. But unlike my friend, I made the choice, not just once but at many critical junctures in my life, not to take antidepressants. Because I knew that depression doesn’t necessarily come from a chemical imbalance, I knew that SSRIs would hardly be a silver bullet or the only thing that would help. I also thought about what side effects they would have. One of the primary reasons I avoided antidepressants is because a common side effect of SSRIs is disruption to sleep. My mood is very responsive to sleep, and I worried that I would just be creating a whole new set of problems for myself; a number of people end up with prescriptions for both sleeping pills and SSRIs. The possibility of sleep disruptions, the fact that my mood was very responsive to other interventions, and other potential side-effects led me to my decision.

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I do not think there is a correct answer to the question of whether any particular individual should take SSRIs. I can imagine someone in my shoes whose symptoms were more severe and had tried other options making a different decision. But the persistence of the chemical myth of depression obfuscates this kind of decision-making. Though mental health professionals and academic researchers understand the distinction between whether and how a treatment works, these two things come hand in hand for patients, and it has been disingenuous to pretend otherwise.

One of the main reasons my friend was so upset about the serotonin study was because she was now left with a great many questions. If she wasn’t depressed because of serotonin levels, how was she to understand her propensity to depression? Was something else wrong with brain? Her genetics? Most heartbreakingly, she wondered whether it was that she was simply weak. The serotonin model of depression had not only played a part in her decision to take antidepressants; it shaped how she thought about herself.

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I have spent a great many years biting my tongue when friends or acquaintances described their depression in terms of chemical imbalances. I hesitated in part because I was fearful of affecting their treatment, something I did not feel professionally qualified to weigh in on. But my biggest fear was intruding on the way in which they understood themselves and their lives.

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Because I have seen myself and my tendency toward depression in different terms, the results of the study have not disrupted my understanding of myself. Though I have sometimes wondered why I seem more inclined to low mood than other people and idly wonder whether it some variation in my particular neurochemistry or genetics, for the most part, when I am going through a depressive period, I recognize its relationship to something that is happening in my life which needs resolving or the fact that I work in a particularly demanding field. I am not suggesting that SSRIs prevent people from considering what might underlie their depression, or that in all cases depression is situational. But when such a compelling story is put forward by authoritative sources, one that explains so tidily why someone feels the way they do and what can be done about it, people tend not to look elsewhere for explanations or solutions. Just as the chemical imbalance myth has clouded making choices about treatment, it has altered how people understand themselves and their lives.

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It is a platitude to say that different treatments work for different people, but I find it interesting that both me and my friend have ended up in similar contented places. One of the reasons the study has been so painful for so many people is the sheer variety of experiences. Those who, like me, have refrained from taking SSRIs feel faintly resentful for the many years that they have been made to feel irrational about their choice. More tragic are the people like my friend who are now questioning their choices and their understanding of themselves. More tragic still are those patients who had an adverse reaction to SSRIs and have spent many years trying to make the psychiatric establishment acknowledge the myth and the way in which it has hidden the trade-offs associated with SSRIs and other psychiatric drugs. Then there are the many patients for whom SSRIs have been beneficial and continue to advocate for their use in the fear that others will miss out on life changing treatment.

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On the other side of the fence, I have colleagues I trust and respect with a wide spectrum of views. What is striking is that once you put the bruised egos and the usual financial vested interests aside, the debates, vicious as they are, seem mostly conducted in utter good faith. Both sides convinced that the other is not only mistaken but in danger of harming vulnerable patients either by peddling dangerous, ill-evidenced treatments or through vilifying treatments that many had found helpful. Though it has been upsetting, I cannot help but find it moving that for most parties involved, the priority is the patient and their well-being.

State of Mind is a partnership of Slate and Arizona State University that offers a practical look at our mental health system—and how to make it better.

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