Nearly 10 percent of all Americans will experience symptoms of depression each year. One of the common forms of treatment includes a combination of therapy and antidepressants. According to the CDC, about 13 percent of Americans over the age of 18 were taking antidepressants between 2015 and 2018. The most commonly prescribed form of these is called selective serotonin reuptake inhibitors (SSRIs), developed to alter the flow of serotonin in the brain.
I am one of millions who takes an SSRI, one called sertraline, to control symptoms of anxiety, depression, and obsessive-compulsive disorder. Before I spoke to a psychiatrist about taking this medication, I dealt with feelings of impending doom and fear that came on a whim, as well as dozens of intrusive thoughts and emotions every minute. Basically, it’s like having your own troublemaker yelling at you all day. Taking the medication has been immensely helpful to me, as it has been to many others.
And that makes it all the more strange to acknowledge that, as with many other complex illnesses, researchers are still unsure what exactly causes depression and whether serotonin is a major culprit. In the 1960s, scientists accidentally discovered that certain medications used as sedatives helped relieve depression. Since these drugs acted on the serotonin system, it led to “a very simplistic idea that low serotonin levels lead to depression,” Gerard Sanacora, a Yale University psychiatrist and director of the Serotonin Program, told The Daily Beast. Yale Depression Research.
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Most scientists now adhere to the idea that there are many genetic, social, and biological factors that contribute to depression; and yet the idea of a chemical or serotonin imbalance is caught up in the popular spirit. It has remained largely thanks to its prominent placement in advertisements for drugs like Prozac in the late 1980s, even as psychiatric research was already changing its perspective.
That brings us to the current debate about SSRIs. Most neuroscientists, psychiatrists, and doctors who study and treat depression agree: antidepressant medications like SSRIs work just as well as cognitive therapy. With proper treatment, depression remission rates can range from 5 percent to 50 percent. There is no doubt that people like me are finding real relief from these medications.
But if depression isn’t as linked to serotonin levels as we once thought, then the problem arises that we don’t really know how SSRIs work and why they might help some depressed people. There are several promising theories suggesting that they play a role in mediating gut bacteria to help the brain grow new cells and retrain itself to create larger and more complex physiological changes beyond simply raising serotonin levels. But none of these theories have been proven yet.
The ensuing discussion has turned into a full-blown debate, pitting mainstream psychiatry against a minority of researchers who don’t believe antidepressants really work.
Every few years, a new series of studies emerges from the shadows, supposedly “debunking” the notion of the serotonin hypothesis. These studies suggest that depression results from social factors or is caused by traumatic experiences, and that antidepressants don’t work, numb emotions, or actively cause harm. Rather than medication, they believe that depression is best treated solely through therapy.
The disputes between academics and competing researchers are as intense and fierce as any other fight that takes place on the Internet, with Twitter fights, opinion articles for groups of experts and the media themselves. The dismal history of the pharmaceutical industry further fuels skepticism about the efficacy of antidepressants. When clinical trials of antidepressants failed to deliver, drug companies essentially buried the evidence and skewed the record in favor of antidepressants, only exacerbating mistrust of these drugs and their manufacturers.
Adding fuel to the fire, a recent review study published in the journal Molecular Psychiatry re-evaluated decades of previous data on serotonin levels in depression, found no evidence of the link between the two, and offered this as evidence that SSRIs either don’t work or only work by blunting emotions. This conclusion drew criticism from many psychiatrists and doctors (the study didn’t even look at 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 this effect of numbing the emotions, and otherwise what the evidence shows is these very small differences between the drugs and the placebo,” said Joanna Moncrieff, a psychiatrist at University College London who directed the study. study, she told The Daily Beast. “Antidepressants are drugs that change the normal state of your brain, it is generally not a good idea to do so [that] long-term.”
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Moncrieff herself is an influential figure in what is called “critical psychiatry”. The Critical Psychiatry Network, co-chaired by Moncrieff, describes the movement on its website: “It represents a scientific challenge to claims about the nature and causes of mental disorders and the effects of psychiatric interventions.” The researchers associated with this movement advocate against drug use for mental health conditions and have even promoted COVID-19 conspiracies.
If depression is caused by the interplay of stressful events and biology, as some within the Critical Psychiatry Network argue, Sanacora doesn’t understand why this means antidepressants don’t work. “I just don’t follow the logic,” she said.
Four other experts who spoke to The Daily Beast specifically rejected Moncrieff’s findings, notably emphasizing that her and her team’s paper crudely conflates two hypotheses under the serotonin theory. There is the well-known chemical imbalance hypothesis, which suggests that a deficit in the neurotransmitter serotonin in the body leads to depression. But according to Roger McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, “the notion of a chemical imbalance in the brain has never been presented as a coherent, comprehensive, evidence-based proposition.”
Instead, the most prevalent serotonin hypothesis that psychiatry takes seriously, and which McIntrye and others argue is supported by evidence, is that a dysregulation of the entire body’s serotonin system is what contributes to clinical depression. This includes problems with the number of receptors available to bind serotonin, problems with the way cells are activated, and many other disturbances at the biomolecular level. They argue that Moncrieff is wrong when it comes to making the grand claim that there is no evidence of serotonin’s involvement in depression.
Furthermore, not knowing the mechanism of a drug is not a sufficient reason to avoid its use if it can be shown to help people. “We’re very confident that SSRIs work for depression,” Tyler Randall Black, a child and adolescent psychiatrist at Children’s Hospital of British Columbia, told The Daily Beast. “There’s lots and lots of evidence showing us that they work, but not why they work.” McIntrye pointed to the fact that we don’t even fully know how Tylenol works, even though it’s one of the most widely used pain relievers in the world. Tylenol also affects the brain in unexpected ways: while it numbs social or psychological pain, that’s no reason to take it off the market.
Vilifying these drugs can have unintended consequences because the therapy is often unavailable, making SSRIs the only accessible option. “Demand for mental health care far outstrips available access,” Sanacora said, adding that many Americans must wait months to see a good cognitive behavioral therapist. Also, abruptly deciding to stop taking SSRIs can be dangerous: one in five patients who do this 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 simple way to explain a complex disorder like depression, they noted that it has compounded downsides over time. The history of a “‘chemical imbalance’ narrative has negatively influenced patient decision-making and patient self-understanding,” Awais Aftaib, a psychiatrist at Case Western Reserve University in Cleveland, Ohio, told the Daily Beast.
Phil Cowen, a psychopharmacologist at the University of Oxford in the UK, told The Daily Beast that socioeconomic status is a contributing factor in depression, leading those in the critical space of psychiatry to believe that “it gives power to doctors and industry” over patients. Ironically, he ignores the millions of “experienced people” who have been helped with antidepressants.
Still, the million dollar question remains: How do SSRIs work? Aftaib explained that a leading new hypothesis is that they encourage the creation of new neurons and new connections between neurons within the brain. The hippocampus, a seahorse-shaped region of the brain important for memory and learning, shrinks and loses neurons when depression hits. SSRIs appear to stimulate the production of neural stem cells, which integrate into the hippocampus to restore its function and structure. Other studies suggest that SSRIs help the brain reconfigure the connections that cause the clinical symptoms associated with depression.
He also added that SSRIs might work through different mechanisms in different individuals, so treatments may need to be more tailored to each case.
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And more specific individual treatments may require psychiatrists to be more honest with their patients about what we do and don’t know about these medications, rather than presenting an oversimplified (and totally inaccurate) explanation.
Black is already trying to do that with his patients: “I’m saying we know for sure that it affects serotonin, but we don’t know how that changes your brain and we don’t know if you’re lacking in serotonin to begin with.” He found that these open discussions about what we know so far about therapy and medication pay off in the long run, and many of his patients will still choose to take the antidepressant as part of their quest to find what works best for them. they.
Read more at The Daily Beast.
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