The debate over the effects of antidepressants is putting millions of people at risk

Nearly 10 percent of all Americans experience symptoms of depression each year. One common form of treatment is a combination of therapy and antidepressants. According to the CDC, approximately 13% of Americans over the age of 18 were taking antidepressants between 2015 and 2018. The most commonly prescribed form is Selective Serotonin Reuptake Inhibitors (SSRIs), designed to alter the flow of serotonin in the brain.

I am one of the millions of people who use the SSRI sertraline to manage symptoms of anxiety, depression and obsessive compulsive disorder. Before talking to a psychiatrist about taking this drug, I struggled with the feeling of impending doom and fear that came on a whim, as well as dozens of intrusive thoughts and emotions every minute. It’s basically like your own Heckler yelling at you all day long. Taking the drug was extremely helpful for me, as it was for many others.

And that makes it even stranger to recognize that, as with many other complex diseases, scientists are still unsure what causes depression or whether serotonin is one of the main culprits. In the 1960s, scientists accidentally discovered that certain medications used as sedatives helped relieve depression. Because these drugs acted on the serotonin system, this led to “the very simplistic idea that low serotonin levels lead to depression,” said Gerard Sanacora, a psychiatrist at Yale University and director of the Yale Depression Research Program, to The Daily Beast.

Most scientists now hold the view that there are many genetic, social, and biological causes of depression; and yet the idea of ​​a chemical or serotonin imbalance got stuck in the popular spirit of the time. It survived largely because it was featured in advertisements for drugs like Prozac in the late 1980s – even when psychiatric research was already changing its perspective.

This brings us to the current SSRI debate. Most neuroscientists, psychiatrists, and clinicians who study and treat depression agree: Antidepressants like SSRIs work just as well as cognitive therapy. With proper treatment, rates of depression remission can range from 5 to 50 percent. There is no doubt that people like me find real relief with these drugs.

But if depression is not as related to serotonin levels as we once thought, then the problem arises that we don’t really know how SSRIs work or why they can help some people with depression. There are several promising theories suggesting that they play a role in mediating gut bacteria by helping the brain grow new cells and require itself, creating larger and more complex physiological changes beyond simply raising serotonin levels. But none of these theories has yet been proven.

A discussion ensued that turned into a wide-ranging debate, contrasting mainstream psychiatry with a minority of researchers who believe that antidepressants actually don’t work.

Every few years, a new wave of research emerges from the shadows, allegedly “refuting” the notion of the serotonin hypothesis. These studies suggest that depression is either caused by social factors or caused by traumatic experiences, and that antidepressants either don’t work, suppress emotions, or actively cause harm. Instead of medications, they believe, treating depression is better only through therapy.

A discussion ensued that turned into a wide-ranging debate, contrasting mainstream psychiatry with a minority of researchers who believe that antidepressants actually don’t work.

Disputes between competing scientists and researchers are just as intense and fierce as any other struggle that takes place on the Internet – including Twitter feuds, articles for think-tanks and news websites themselves. The dark history of the pharmaceutical industry has further fueled skepticism about the effectiveness of antidepressants. When clinical trials of antidepressants failed to produce the expected results, drug companies essentially buried the evidence and spoiled the results in favor of antidepressants – which only exacerbated the distrust of these drugs and their makers.

Pouring Oil on the Fire, one of the latest review studies published in the journal Molecular psychiatry analyzed decades of data on serotonin levels in depression, finding no evidence of a link between the two, and providing this as evidence that SSRIs do not work, or only work by blunting emotions. This conclusion was criticized by many psychiatrists and clinicians – the study did not even analyze whether antidepressants work – but with the support of the authors, the right-wing media was pushing the message anyway.

“If there are benefits, I would say they are due to the emotional paralysis effect, and the evidence shows that there is very little difference between drugs and placebo,” Joanna Moncrieff, the psychiatrist at University College London who led the study, told The Daily Beast. “Antidepressants are drugs that alter the normal state of the brain, and they’re generally not a good idea [that] for longer period of time.”

Moncrieff herself is an influential figure in the so-called “critical psychiatry”, The Critical Psychiatry Network, of which Moncrieff co-chaired, describes the movement on her website: “It poses a scientific challenge to claims about the nature and causes of mental disorders and the effects of psychiatric interventions.” Scientists behind the movement have advocated against the use of drugs for mental illness and have even promoted COVID-19 conspiracies.

If depression is caused by an interaction of stressful events and biology, as some members of the Critical Psychiatry Network have claimed, Sanacora does not understand why this means that antidepressants are not working. “I just don’t follow logic,” he said.

Four other experts who spoke to The Daily Beast explicitly rejected Moncrieff’s findings, emphasizing in the first place that her article and her team’s article roughly links the two hypotheses to the serotonin theory. There is a fairly well-known hypothesis of chemical imbalance that suggests that a deficiency of the serotonin neurotransmitter in the body leads to depression. But according to Roger McIntyre, professor of psychiatry and pharmacology at the University of Toronto, “the concept of chemical imbalance in the brain has never been presented as a coherent, comprehensive, evidence-based proposition.”

Instead, the more dominant hypothesis about serotonin, which psychiatry takes seriously, and which McIntrye et al. Argues, is supported by evidence, is that dysregulation of the body’s entire serotonin system is what contributes to clinical depression. This includes problems with the amount of receptors available for serotonin binding, problems with cell fire, and many other disruptions at the biomolecular level. They argue that Moncrieff is wrong when it comes to the great claim that there is no evidence of serotonin involvement in depression.

The concept of chemical imbalance in the brain has never been presented as a coherent, comprehensive, evidence-based proposition.

Roger McIntyre, University of Toronto

Moreover, ignorance of the drug’s mechanism of action is not reason enough to prevent its use if it is visibly helping people. “We are very confident that SSRIs work on depression,” told The Daily Beast Tyler Randall Black, a child and adolescent psychiatrist at the University of British Columbia. “There are risks and risks of evidence showing us that they work, but not why they work.” McIntrye pointed out that we don’t even know exactly how Tylenol works – despite the fact that it’s one of the most commonly used painkillers worldwide. Tylenol also affects the brain in unexpected ways – although it numbs social or psychological pain, it is not a basis for taking it off the market.

Violating these drugs can have unintended consequences as therapy is often unavailable, making SSRIs the only available option. “The demand for psychiatric care far exceeds the available access,” Sanacora said, adding that many Americans have to wait months to see a good cognitive behavioral therapist. Moreover, a sudden decision to stop taking SSRIs can be dangerous: one in five patients who do so will experience flu-like symptoms, insomnia, imbalance, and other symptoms that can last for a year.

While psychiatrists who spoke to The Daily Beast emphasized that the serotonin hypothesis was a way of simply explaining a complex disorder such as depression, they emphasized that it had negative sides over time. The “chemical imbalance” narrative has negatively impacted patient decision making and self-understanding, said Daily Beast Awais Aftab, a psychiatrist at Case Western Reserve University in Cleveland, Ohio.

The demand for psychiatric care far exceeds the available access.

Gerard Sanacora, Yale University

Phil Cowen, a psychopharmacologist at the University of Oxford in the UK, told The Daily Beast that socioeconomic status is a contributing factor to depression, prompting those in critical psychiatry to believe that it is “empowering doctors and industry” over patients . Ironically, it ignores the millions of “experienced people” who have been helped by antidepressants.

The million-dollar question still remains: How do SSRIs work? Aftab explained that the new leading hypothesis is that they encourage the formation of new neurons and new connections between neurons in the brain. The hippocampus, a seahorse-shaped brain region important to memory and learning, contracts and loses neurons when depression sets in. SSRIs appear to stimulate the production of neural stem cells that integrate into the hippocampus to restore its function and structure. Other research suggests that SSRIs help the brain change the connections that cause clinical symptoms associated with depression.

He also added that SSRIs can work through different mechanisms in different people, so treatment may be more tailored to individual cases.

More specifically, individual therapies may require psychiatrists to be more honest with their patients about what we know and don’t know about these drugs, as opposed to giving overly simplistic (and even inaccurate) explanations.

Black is already trying to do this with his patients: “I say we know for sure that it affects serotonin, but we don’t know how it changes your brain, and we don’t know that you are low on serotonin at first.” He found that these open discussions of what we know so far about treatments and medications pay off in the long run, and many of his patients will continue to choose to take antidepressants as part of their research to find what is right for them the best.

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