I am one of the millions who take an SSRI, one called sertraline, to manage symptoms of anxiety, depression and obsessive compulsive disorder. Before talking to a psychiatrist about using this medication, I dealt with feelings of impending doom and fear that would appear on a whim, as well as dozens of intrusive thoughts and emotions every minute. Basically, it’s like your own caller calling you all day. Taking the medication has been very helpful for me, as it has for many others.
And that makes it even stranger to acknowledge that, as with many other complex illnesses, researchers still don’t know exactly what causes depression and whether serotonin is a major culprit. In the 1960s, scientists accidentally discovered that certain drugs used as sedatives helped relieve depression. Because these drugs acted on the serotonin system, it led to “a very simplistic idea that low serotonin levels lead to depression,” said Gerard Sanacora, a psychiatrist at Yale University and director of the Program on ‘Yale Depression Research, in The Daily Beast.
Most scientists now adhere to the idea that there are many genetic, social, and biological contributors to depression; and yet the idea of a chemical or serotonin imbalance is stuck in the popular zeitgeist. It has endured in large part because of its prominent placement in ads for drugs like Prozac in the late 1980s, even as psychiatric research was already changing its outlook.
This brings us to the current SSRI debate. Most neuroscientists, psychiatrists, and doctors who study and treat depression agree: antidepressant drugs like SSRIs work just as well as cognitive therapy. With the right treatment, depression remission rates can range from 5 to 50 percent. There is no doubt that people like me find real relief from these drugs.
But if depression isn’t as tied to serotonin levels as we once thought, then it raises the issue that we don’t really know how SSRIs work and why they might help some depressed people. There are several promising theories that suggest they play a role in mediating gut bacteria, to help the brain grow new cells and require itself, to create larger and more complex physiological changes beyond simply increasing serotonin levels. . But none of these theories have been proven yet.
The ensuing discussion has turned into a wide-ranging debate, pitting mainstream psychiatry against a minority of researchers who don’t believe antidepressants actually work.
Every few years, a new wave of studies emerges from the shadows, supposedly “debunking” the notion of the serotonin hypothesis. These studies suggest that depression is the result of 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 through therapy alone.
“The ensuing discussion has turned into a wide-ranging debate, pitting mainstream psychiatry against a minority of researchers who don’t believe antidepressants actually work.“
The fights between competing academics and researchers are as intense and vicious as any other fight that occurs on the Internet, with Feuds on Twitter, opinion articles for think tanks and the media themselves. The dark history of the pharmaceutical industry further fuels skepticism about the effectiveness of antidepressants. When clinical trials of antidepressants failed to confirm the expected results, drug companies essentially buried the evidence and skewed the record in favor of antidepressants, which has only exacerbated mistrust of these drugs and their manufacturers.
Adding fuel to the fire, a recent review study published in the journal Molecular Psychiatry He re-evaluated decades of past data on serotonin levels in depression, found no evidence of a link between the two, and offered it as evidence that SSRIs either don’t work or only work by dampening emotions. This conclusion drew criticism from many psychiatrists and doctors (the study did not even look at whether antidepressants work), but with the support of the study authors, the right-wing media pushed this message out of all manners
“If there are benefits, I would say they are due to this numbing effect of emotions, and otherwise what the evidence shows are these very small differences between drugs and placebo,” said Joanna Moncrieff, a psychiatrist at the University College London who led the study, told The Daily Beast. “Antidepressants are drugs that change the normal state of the brain, so it’s generally not a good idea to do that. [that] long-term”.
Moncrieff herself is an influential figure in what is called “critical psychiatry,” The Critical Psychiatry Network, which Moncrieff co-chairs, describes the movement on its website: “It is a scientific challenge to claims about the nature and causes of mental disorder and the effects of psychiatric interventions.” Researchers associated with this movement advocate the use of drugs for mental health problems, and have even promoted COVID-19 conspiracies.
If depression is caused by the interaction of stressful events and biology, as some in the Critical Psychiatry Network argue, Sanacora doesn’t follow why that means antidepressants don’t work. “I don’t follow logic,” he said.
Four other experts who spoke to The Daily Beast specifically rejected Moncrieff’s findings, noting in particular that her and her team’s paper crudely conflates two hypotheses under the serotonin theory. There is the chemical imbalance hypothesis that is quite well known, 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 your brain has never been presented as a coherent, comprehensive, evidence-based proposition.”
Instead, the more prevalent serotonin hypothesis that psychiatry takes seriously, and which McIntrye and others argue is supported by evidence, is that a dysregulation of the body’s entire serotonin system is what contributes to clinical depression. This includes problems in the amount of receptors available for serotonin to bind to, problems with how cells fire, and many other disruptions at the biomolecular level. They argue that Moncrieff is wrong when it comes to making the big claim that there is no evidence for the involvement of serotonin in depression.
“The notion of a chemical imbalance in your brain has never been presented as a coherent, comprehensive, evidence-based proposition.“
— Roger McIntyre, University of Toronto
Also, not knowing the mechanism of a drug is not a good enough reason to avoid using it if it is showing that it is helping people. “We’re very confident that SSRIs work 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 shows they work, but not why they work.” McIntrye pointed to the fact that we don’t even fully know how Tylenol works, despite it being one of the most widely used pain relievers worldwide. Tylenol also affects the brain in unexpected ways, although it numbs social or psychological pain, that’s no reason to take it off the market.
The vilification of these drugs can have unintended consequences because therapy is often unavailable, making SSRIs the only accessible option. “The demand for mental health care far exceeds the available access,” Sanacora said, adding that many Americans have to wait months to see a good cognitive behavioral therapist. Also, suddenly deciding 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 one way to simply explain a complex disorder like depression, they emphasized that it has fostered disadvantages over time. The story of a “chemical imbalance” narrative has negatively influenced patient decision-making and patient self-understanding, Awais Aftab, a psychiatrist at Case Western Reserve University in Cleveland, Ohio, told the Daily Beast.
“Demand for mental health care far exceeds available access.“
— Gerard Sanacora, Yale University
Phil Cowen, a psychopharmacologist at the University of Oxford in the United Kingdom, told The Daily Beast that socioeconomic status is a contributing factor to depression, leading those in the critical space of psychiatry to believe which “empowers doctors and industry” over patients. Ironically, it ignores the millions of “experienced people” who were helped by anti-depressants.
Still, the million dollar question remains: How do SSRIs work? Aftab explained that a new leading 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 rewire the connections that cause the clinical symptoms associated with depression.
He also added that SSRIs could work through different mechanisms in different individuals, so treatments may need to be more tailored to each case.
And 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, rather than giving an oversimplified (and frankly inaccurate) explanation.
Black is already trying this with his patients: “I say we know for sure that it affects serotonin, but we don’t know how that changes your brain and we don’t know that you lack serotonin to begin with.” He has 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 they works better