A popular depression theory hasn’t been ‘debunked’ by a new review

A new paper that reviews the evidence surrounding the serotonin ‘chemical imbalance’ theory of depression has caused an online firestorm, with figures from across psychiatry commenting on the study’s merits and limitations. In this article, we cut through the hype and take a look at what the paper has changed our understanding of depression.

Psychiatry has long since abandoned the “chemical imbalance” theory.

The review article, published by an international research team whose first author, Professor Joanna Moncrieff, aimed to systematically assess the available evidence for and against the serotonin theory of depression. The team explains this theory near the beginning of their article: “[The theory is] the idea that depression is the result of abnormalities in brain chemicals, particularly serotonin (5-hydroxytryptamine or 5-HT). The theory has been around for decades, but their general conclusion is that it is not correct, given that there does not appear to be a measurable link between serotonin levels and depression.

The reaction of many scholars to this discovery can be summed up, briefly, as “Of course! In comments to the UK-based Science Media Centre, Dr Michael Bloomfield, Consultant Psychiatrist and Head of the Translational Psychiatry Research Group at University College London (UCL), said: “The findings of this overall review are really not surprising. Depression has many different symptoms and I don’t think I’ve come across any serious scientists or psychiatrists who believe that all causes of depression are caused by a simple chemical imbalance of serotonin.

Professor Phil Cowen, Professor of Psychopharmacology at Oxford University, said: “No mental health professional would currently endorse the idea that a complex heterogeneous condition like depression stems from a deficiency of one single neurotransmitter.

Professor Allan Young, Director of the Center for Affective Disorders at King’s College London, said: “Most psychiatrists adhere to the biopsychosocial model and very few people subscribe to a simple ‘chemical imbalance’ theory.

While the review has made headlines for “debunking” the serotonin imbalance theory, the reaction of many researchers suggests that this idea, in fact, has not been seriously addressed in the field itself for decades. years.

Psychiatry forgot to tell the public that it abandoned the ‘chemical imbalance’ theory a long time ago

If you’ve read the point above and felt rather perplexed to discover that the chemical imbalance theory has actually been in the academic trash for a few years, you’re not alone. The review authors pointed to one study (n=893) that found that 88.1% of respondents believed that a “chemical imbalance” was a cause of depression. This idea, the authors point out, has been heavily promoted by pharmaceutical companies aiming to sell compounds that are selective serotonin reuptake inhibitors (SSRIs). Eli Lilly, for example, promoted his compound Prozac in 2008 with the following: “Many scientists believe that an imbalance of serotonin, one of these neurotransmitters, may be an important factor in the development and the severity of depression. PROZAC can help correct this imbalance by increasing the supply of serotonin to the brain.

This attitude was not just a marketing ploy adopted by an unwitting audience – Dr. Christopher Lane of Northwestern University pointed out in a commentary in psychology today a 2005 study that explored the disconnect between advertisements for SSRIs and the scientific evidence supporting their use. Lane quotes Daniel Carlat, editor of the Carlat Psychiatry Report: “I will often say something like how Zoloft works is that it increases the level of serotonin in your brain (or synapses, neurons) and, presumably, the reason you are depressed or anxious is that you have some kind of disability. And I say that [chuckles] not because I really believe in it, because I know that the evidence is really not there to allow us to understand the mechanism.

Lane further points out that another study, this time a survey of 237 psychology students, found that 46% had heard a doctor explain the chemical imbalance theory to them. While academia has long dismissed the disequilibrium theory, this message does not seem to have reached the public.

Whether SSRIs are effective or not is not in question.

While the original review article focuses primarily on serotonin theory, an accompanying article by Moncrieff and his co-author Mark Horowitz in The conversation took a different approach, arguing that the evidence against the serotonin hypothesis also refutes the need for SSRIs, full stop. “We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe,” they write. This confusion has been a particular source of frustration among commentating psychiatrists. “Many of us know that taking paracetamol can be helpful for headaches, and I don’t think anyone believes that headaches are caused by a lack of paracetamol in the brain,” Young writes. “There is consistent evidence that antidepressant medications can be helpful in treating depression and can save lives.”

Young’s statement is supported by a significant body of research. While a separate debate exists around the critical element of whether antidepressants are more helpful than placebo, Moncrieff and Horowitz’s review cannot add any evidence to the pile anyway, although Moncrieff has previously written peer-reviewed articles highly critical of a drug-based approach to mental health treatment. “It’s important to point out that this study didn’t actually look directly at the effectiveness of antidepressants. Antidepressants with serotonergic activity were already used effectively for patients with depression before the theory of serotonergic changes in depression, commented Dr Livia de Picker, postdoctoral researcher at the University of Antwerp.

Is depression even a single disease?

While Moncrieff’s review focuses on refuting the idea of ​​a particular cause of depression, perhaps the debate should instead focus on the idea that depression is a single disease. “Today, it is widely accepted that depression is a heterogeneous disorder with potentially multiple underlying causes,” says Professor Gitte Moos Knudsen of University Hospital Copenhagen, Denmark. As we have reframed cancer not as one but as multiple diseases, perhaps mental health disorders like depression should be reframed as resulting from many different environmental and biological factors. Abandoning the single serotonergic focus of the “chemical imbalance” model is a necessary part of this mindset shift, but more work needs to be done to reframe public perceptions of the complex biology of depression.

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