The debate over how antidepressants work puts millions of people at risk

The debate over how antidepressants work puts millions of people at risk

Nearly 10 percent of all Americans experience symptoms of depression each year. One common form of treatment is combination therapy and antidepressants. According to the Centers for Disease Control and Prevention (CDC), about 13 percent of Americans over the age of 18 were taking antidepressants between 2015 and 2018. The most common form of these medications are called selective serotonin reuptake inhibitors (SSRIs), which are Developed to alter the flow of serotonin in the brain.

I am one of the millions who take SSRIs – one called sertraline, to manage symptoms of anxiety, depression and obsessive-compulsive disorder. Before speaking to a psychiatrist about taking this drug, I dealt with feelings of doom and impending dread that came on on a whim, as well as dozens of intrusive thoughts and feelings every minute. Basically, it’s like having your own screaming all day long. Taking medication has been very helpful for me, as it has for many other people.

This makes it all the more surprising to realize that, as with many other complex diseases, researchers still aren’t sure exactly what causes depression, and whether serotonin is one of the main culprits. In the 1960s, scientists accidentally discovered that some medications that are used as sedatives help relieve depression. Because these drugs act on the serotonin system, they have led to “the very simplistic idea that low levels of serotonin lead to depression,” Gerard Sanakura, MD, a psychiatrist at Yale University and director of the Yale Depression Research Program, told The Daily Beast.

Most scientists now adhere to the idea that there are many genetic, social, and biological factors that contribute to depression; However, the idea of ​​a chemical or serotonin imbalance stuck in the popular zeitgeist. It has survived largely thanks to its prominent position in advertisements for drugs like Prozac in the late 1980s — even when psychological research was already changing its perspective.

This brings us to the current debate about SSRIs. Most neuroscientists, psychiatrists, and physicians who study and treat depression agree that: Antidepressant medications such as SSRIs work as well as cognitive therapy. With proper treatment, recovery rates from depression can range from 5 to 50 percent. There is no doubt that people like me find real relief thanks to these medicines.

But if depression isn’t quite related to serotonin levels as we previously thought, it raises the problem that we don’t really know how SSRIs work and why they might help some people with depression. There are several promising theories suggesting that it plays a role in mediating gut bacteria, to help the brain grow new cells that need itself, to create larger and more complex physiological changes that go beyond simply raising serotonin levels. But none of these theories have yet been proven.

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The discussion that followed turned into a full-blown debate, as mainstream psychiatry pitted against a minority of researchers who don’t believe antidepressants actually work.

Every few years, a new series of studies emerges from the shadows, presumably to “refute” the idea of ​​the serotonin hypothesis. These studies indicate that depression is either the result of social factors or the result of traumatic experiences, and that antidepressants either do not work, numb feelings, or cause actual harm. Instead of medication, they believe depression is best treated with just treatment.

The discussion that followed turned into a full-blown debate, as mainstream psychiatry pitted against a minority of researchers who don’t believe antidepressants actually work.

The feuds between rival academics and researchers are as intense and brutal as any other online combat – featuring Twitter Disputesand opinion articles for think tanks and news outlets themselves. The suspicious history of the pharmaceutical industry fuels further doubts about the effectiveness of antidepressants. When clinical trials of antidepressants did not lead to the hoped-for results, drug companies essentially buried evidence and biased the registry in favor of antidepressants—which only exacerbated mistrust about these drugs and their makers.

Adding fuel to a fire, a recent review study published in the journal Molecular Psychiatry It reassessed decades of previous data on serotonin levels in depression, found no evidence of a link between the two and presented this as evidence that SSRIs do not work, or only work by relieving feelings. This finding drew criticism from many psychiatrists and clinicians — the study didn’t even analyze whether antidepressants work — but with the support of the study’s authors, the right-wing media pushed this message anyway.

“If there are benefits, I would say they are due to the effect of emotional sedation, and other than that, what the evidence shows are these very small differences between the medication and the placebo,” Joanna Moncrieff, a psychiatrist at University College London who led the study, told the Daily Best. Antidepressants are drugs that alter the normal state of your brain, in general, they are not a good idea to do [that] The long-term. “

Moncrieff herself is an influential figure in so-called “critical psychiatry,” the Critical Psychiatry Network, of which Moncrieff co-chairs, describes the movement on its website: “It poses a scientific challenge to claims about the nature and causes of mental disorders and the effects of psychological interventions.” Researchers associated with this movement advocate the use of drugs in mental health conditions and even promote COVID-19 conspiracies.

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If depression is caused by the interaction of stressful events with biology, as some within the Critical Psychiatry Network argue, Sanacora does not track why antidepressants are ineffective. “I just don’t follow logic,” he said.

Four other experts who spoke to The Daily Beast responded specifically about Moncrieff’s findings, notably emphasizing that her and her team’s research confuses two hypotheses under the serotonin theory. There is a well-known chemical imbalance hypothesis, which suggests that there is a deficit in the neurotransmitter serotonin in the body that leads to depression. But according to Roger McIntyre, professor of psychiatry and pharmacology at the University of Toronto, “the idea of ​​a chemical imbalance in your brain has not been put forward as a coherent, comprehensive, and evidence-based proposal.”

Instead, the most popular serotonin hypothesis that psychiatry takes seriously and that McIntrye and others argue is supported by evidence, is that dysregulation of the whole-body serotonin system is what contributes to clinical depression. This includes problems with the amount of receptors available to bind serotonin, problems with how cells release, and many other disorders at the biomolecular level. They argue that Moncrieff is wrong when it comes to the grand claim that there is no evidence that serotonin is involved in depression.

The idea of ​​a chemical imbalance in your brain has never been put forward as a coherent, comprehensive, and evidence-based proposition.

Roger McIntyre, University of Toronto

Furthermore, not knowing the mechanism of the drug is not a sufficient reason to prevent its use if it is clearly helping people. “We are very confident that SSRIs work for depression,” Tyler Randall Black, MD, a child and adolescent psychiatrist at Children’s Hospital of British Columbia, told The Daily Beast. “There is a lot of evidence to show us that it works, but not why it works.” McIntrye pointed to the fact that we don’t quite know how Tylenol works either – despite the fact that it is one of the most widely used pain relievers worldwide. Tylenol also affects the brain in unexpected ways – although it numbs social or psychological pain, there is no reason to remove it from the market.

Messing with these medications can have unintended consequences because treatment is often unavailable, making SSRIs the only available option. “The demand for mental health care far outpaces what is available,” Sanakura said, adding that many Americans need to wait months to see a good cognitive behavioral therapist. Additionally, making 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 up to a year.

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While psychiatrists who spoke with The Daily Beast asserted that the serotonin hypothesis was a way to simply explain a complex disorder like depression, they highlighted that it reinforced the negative aspects over time. Owais Aftayb, MD, a psychiatrist at Case Western Reserve University in Cleveland, Ohio, told The Daily Beast that the story of a ‘chemical imbalance’ negatively affected a patient’s decision-making and patient self-understanding.

The demand for mental health care far outpaces the available access.

Gerard Sanakura, Yale University

Socioeconomic status is a contributing factor to depression, leading those in the critical field of psychiatry to believe it “gives power to clinicians and industry” over patients, Phil Quinn, a psychopharmacologist at Oxford University in the UK, told The Daily Beast. Ironically, he ignores the millions of “experienced people” who have been helped by antidepressants.

However, the million dollar question remains: How do SSRIs work? Afteb explained that the main new hypothesis is that it encourages the creation of new neurons and new connections between neurons within the brain. The hippocampus, a seahorse-shaped area of ​​the brain important for memory and learning, shrinks and loses neurons when depressed. SSRIs appear to stimulate the production of neural stem cells, which fuse into the hippocampus to restore their function and structure. Other studies suggest that SSRIs help the brain rewire the connections that cause clinical symptoms associated with depression.

He also added that SSRIs may act through different mechanisms in different individuals, so treatments may have to be more customized to each individual case.

More specifically, individual treatments may require psychiatrists to be more honest with their patients about what we know and don’t know about these medications, versus evading a simplistic (and wholly inaccurate) explanation.

Black tries to do just that with his patients: “I’d say we definitely know that it affects serotonin, but we don’t know how that changes your brain and we don’t know that you’re lacking in serotonin to begin with.” He’s found that these open discussions about what we know so far about treatment and medication pay off in the long run, and many of his patients will still choose to take antidepressants as part of their search to find what’s best for them.

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About the Author: Omar Dzaki Khawarizmi