Debate over how antidepressants work puts millions at risk

Nearly 10 percent of Americans experience depressive symptoms each year. A common form of treatment involves a combination of therapy and antidepressants. Between 2015 and 2018, about 13 percent of Americans over the age of 18 were taking antidepressants, according to the CDC. The most commonly prescribed form of these, called selective serotonin reuptake inhibitors (SSRIs), is designed to alter serotonin flux in the brain.

I am one of the millions of people who take an SSRI (one called sertraline) to manage symptoms of anxiety, depression and OCD. Before I spoke to a psychiatrist about taking this drug, I dealt with whims of doom and fear, as well as dozens of intrusive thoughts and emotions every minute. Basically, it’s like having your own questioner yell at you all day long. Taking medication has been very helpful to me, as it has been to many others.

Even stranger, as with many other complex diseases, researchers still aren’t sure exactly what causes depression and whether serotonin is one of the culprits. In the 1960s, scientists stumbled across certain drugs used as sedatives to help relieve depression. Because these drugs act on the serotonin system, it leads to “the very simple idea that low levels of serotonin cause depression,” said Gerard Sanaco, a Yale psychiatrist and director of the Yale Depression Research Program. Ra told The Daily Beast.

Most scientists now insist that depression has many genetic, social and biological factors. Yet the idea of ​​a chemical or serotonin imbalance remains in the prevailing zeitgeist. In the late 1980s, it featured prominently in advertisements for drugs like Prozac, in large part because it persisted — even when psychiatric research had changed its view.

This brings us to the current debate around SSRI. Most neuroscientists, psychiatrists, and clinicians who study and treat depression agree that antidepressants like SSRIs are as effective as cognitive therapy. With the right treatment, depression remission rates can range from 5% to 50%. There is no doubt that people like me are finding real relief with these drugs.

But if depression isn’t related to serotonin levels as we once thought, it raises the question that we don’t really understand how SSRIs work and why they might help some people with depression. There are several promising theories that suggest they play a role in regulating gut bacteria, helping the brain grow new cells and needing itself, producing larger and more complex physiological changes beyond just raising serotonin levels. But none of these theories have been proven.

The ensuing discussion morphed into a full-blown debate, with mainstream psychiatry pitted against a handful of researchers who argue that antidepressants don’t actually work.

Every few years, a flood of new research emerges from the shadows that purportedly “debunks” the concept of the serotonin hypothesis. These studies suggest that depression is either the result of social factors or caused by traumatic experiences, and that antidepressants either don’t work, numb emotions, or actively cause harm. They argue that depression is better treated with treatment alone, rather than medication.

The ensuing discussion morphed into a full-blown debate, with mainstream psychiatry pitted against a handful of researchers who argue that antidepressants don’t actually work.

The quarrel between competing academics and researchers is as fierce and vicious as any other fight on the Internet – with twitter spat, think tank columns and the news media themselves. The shady history of the pharmaceutical industry further fuels doubts about the efficacy of antidepressants. When clinical trials of antidepressants fail to confirm the expected results, drug companies essentially bury the evidence and skew the record in favor of antidepressants — which only fuels mistrust of these drugs and their makers.

Adding fuel to the fire, a review study recently published in the journal Molecular Psychiatry Re-evaluation of data from the past few decades on serotonin levels in depression found no evidence of a link, as evidence that SSRIs do not work or work only by blunting mood. The conclusion drew criticism from many psychiatrists and clinicians—the study didn’t even analyze whether antidepressants worked—but the right-wing media, supported by the study’s authors, got the message out anyway.

“If there are benefits, I’d say they’re due to this mood-numbing effect, otherwise, the evidence shows these very small differences between the drug and the placebo,” led psychiatrist Joanna Moncrieff of University College London. this research. Research, tell The Daily Beast. “Antidepressants are drugs that change the normal state of the brain, and generally speaking, it’s not a good idea [that] Long term. “

Moncrieff himself is an influential figure in so-called “critical psychiatry,” and the Critical Psychiatry Network, which Moncrieff co-chairs, describes the movement on its website: “It raises claims about the nature and causes of mental disorders. scientific challenges, and the impact of psychological interventions.” Researchers associated with the movement advocate against the use of drugs to treat mental health problems and even promote a COVID-19 conspiracy.

If depression is caused by an interplay of stressful events and biology, as some in the Critical Psychiatry Network argue, Sanakola doesn’t understand why that means antidepressants don’t work. “I just don’t follow logic,” he said.

Four other experts who spoke to The Daily Beast specifically refuted Moncrieff’s findings, most notably her and her team’s paper crudely conflating the two assumptions under the serotonin theory. There is a well-known chemical imbalance hypothesis, which suggests that a lack of the serotonin neurotransmitter in the body causes depression. But according to Roger McIntyre, professor of psychiatry and pharmacology at the University of Toronto, “the concept of chemical imbalances in the brain has never been presented as a coherent, comprehensive, evidence-based recommendation.”

Instead, the more general serotonin hypothesis is taken seriously by psychiatry and which McIntrye and others believe is supported by evidence that dysregulation of the body’s entire serotonin system is responsible for clinical depression. This includes questions about the number of receptors available to bind serotonin, how cells fire, and many other disruptions at the biomolecular level. They argue that Moncrief is mistaken when it comes to the grandiose claim that serotonin is linked to depression without any evidence.

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

Roger McIntyre, University of Toronto

Furthermore, if the drug is clearly helping people, not understanding the mechanism of action of the drug is not a sufficient reason to discourage its use. “We are very confident that SSRIs are effective for depression,” Tyler Randall Black, a child and adolescent psychiatrist at the University of British Columbia, told The Daily Beast. “There’s a lot of evidence that they work, but not why.” McIntrye points out that we don’t even fully understand how Tylenol works — even though it’s one of the most widely used painkillers in the world. Tylenol also affects the brain in unexpected ways—while it can numb social or psychological pain, that’s not a reason to remove it from the market.

Discrediting these drugs can have unintended consequences because treatment is often unavailable, making SSRIs the only viable option. “The need for mental health care far outstrips what’s available,” Sanakola said, adding that many Americans wait months to see a good cognitive-behavioral therapist. Additionally, a sudden decision to stop taking an SSRI can be dangerous: One in five sufferers experience flu-like symptoms, insomnia, imbalances and other symptoms that can last up to a year.

While the psychiatrists who spoke with The Daily Beast emphasized that the serotonin hypothesis is a simple way of explaining a complex disorder like depression, they did stress that it can have detrimental effects over time. Awais Aftab, a psychiatrist at Case Western Reserve University in Cleveland, Ohio, told The Daily Beast, “Stories of ‘chemical imbalances’ have had a negative impact on patient decision-making and patients’ self-understanding.”

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

Gerald Sanakola, Yale University

Phil Cowan, a psychopharmacologist at the University of Oxford, UK, told The Daily Beast that socioeconomic status is a factor in depression, leading people in key psychiatry fields to believe it “empowers doctors and the profession”, rather than patients. Ironically, it ignores the millions of “experienced people” who are helped by antidepressants.

Still, the million-dollar question remains: How does SSRI work? Aftab explained that a major new hypothesis is that they encourage the production of new neurons and new connections between neurons within the brain. The hippocampus, a hippocampal-shaped region of the brain important for memory and learning, contracts and loses neurons when depression strikes. SSRIs appear to stimulate the production of neuronal stem cells that integrate into the hippocampus to restore its function and structure. Other research has shown that SSRIs help the brain rewire the connections that lead to clinical symptoms associated with depression.

He also added that SSRIs may work in different individuals through different mechanisms, so treatment may have to be adjusted on a case-by-case basis.

More specifically, individual treatments may require psychiatrists to be more honest with their patients about what we know and don’t know about these drugs, rather than offering simplistic (and downright inaccurate) explanations.

Black has tried this with his patients: “I say we definitely know it affects serotonin, but we don’t know how that changes your brain, and we don’t know that you’re deficient in serotonin in the first place.” He found that from In the long run, these open discussions about what we know so far about treatments and medicines will pay off, and many of his patients will still choose to take antidepressants as part of their search for the medicine that works best for them.

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