Debate over how antidepressants work puts millions at risk

Nearly 10% 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% of Americans over the age of 18 were taking antidepressants between 2015 and 2018. The most commonly prescribed form of these is called a selective serotonin reuptake inhibitor (SSRI), developed to alter the flow of serotonin in the brain.

I am one of millions of people who take an SSRI, called sertraline, to manage symptoms of anxiety, depression, and obsessive-compulsive disorder. Prior to speaking with a psychiatrist about taking this medication, I was dealing with feelings of impending doom and fear that came on a whim, along with dozens of intrusive thoughts and emotions every minute. . Basically, it’s like having your own rowdy yelling at you all day. Taking the drug has been extremely helpful for me, as it has been for many others.

And it makes it all the stranger to recognize 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. Since these drugs acted on the serotonin system, this led to “a very simplistic idea that low levels of serotonin lead to depression,” said Gerard Sanacora, a psychiatrist at Yale University and program director of Yale Depression Research, to The Daily Beast.

Most scientists now buy into the idea that there are many genetic, social and biological contributors to depression; and yet the idea of ​​a chemical or serotonergic imbalance is stuck in the popular zeitgeist. It lingered largely thanks to its prominent place 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 debate around SSRIs. Most neuroscientists, psychiatrists, and clinicians who study and treat depression agree: antidepressants like SSRIs work just as well as cognitive therapy. With the right treatment, remission rates for depression can range between 5 and 50 percent. There is no doubt that people like me find real relief with these drugs.

But if depression isn’t as linked to serotonin levels as we once thought, it raises the issue that we don’t really know how SSRIs work and why they can 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 self-demand, to create larger and more complex physiological changes beyond the simple increase in serotonin levels. But none of these theories have yet been proven.

The ensuing discussion turned into a full 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 either the result of social factors or caused by traumatic experiences, and that antidepressants don’t work, numb emotions, or actively cause harm. Instead of drugs, they believe depression is best treated with therapy alone.

“The ensuing discussion turned into a full debate, pitting mainstream psychiatry against a minority of researchers who don’t believe antidepressants actually work.”

The feuds between academics and competing researchers are just as intense and vicious as any other fight that takes place on the internet, featuring Quarrels on Twitter, editorials for think tanks and the media themselves. The murky 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 case in favor of antidepressants, which only exacerbated distrust of these drugs and their manufacturers.

Adding fuel to the fire, a recent study published in the journal Molecular psychiatry reassessed decades of past data on serotonin levels in depression, finding no evidence of a link between the two and offering this as proof that SSRIs either don’t work or only work by blunting emotions. 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 authors, the right-wing media carried the message anyway.

“If there are benefits, I would say they are due to this emotion numbing effect, and if not, what the evidence shows are these very small differences between the drugs and the placebo,” Joanna Moncrieff , a psychiatrist at University College London who led the study, told The Daily Beast. “Antidepressants are drugs that alter the normal state of your brain, usually it’s not a good idea to do [that] long-term. »

Moncrieff herself is an influential figure in so-called “critical psychiatry,” The Critical Psychiatry Network, which Moncrieff co-chairs, describes the movement on her website: “It scientifically challenges claims about the nature and causes of mental disorders and the effects of psychiatric interventions. Researchers associated with this movement are advocating against the use of drugs for mental health issues and have even encouraged COVID-19 conspiracies.

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

Four other experts who spoke to The Daily Beast specifically pushed back against Moncrieff’s findings, noting in particular that his paper and that of his team grossly confuse two assumptions under the serotonin theory. There is the chemical imbalance hypothesis which is quite well known, which suggests that a deficiency of 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 most common assumption about serotonin that psychiatry takes seriously, and which McIntrye and others say is supported by evidence, is that a dysregulation of the body’s entire serotonergic system is what contributes to clinical depression. This includes problems with the amount of receptors available to bind serotonin, cell firing problems, and many other disturbances at the biomolecular level. They argue that Moncrieff is wrong when it comes to claiming 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, and evidence-based proposition.”

— Roger McIntyre, University of Toronto

Also, not knowing the mechanism of a drug is not a sufficient reason to prevent its use if it is clear that it helps people. “We’re confident that SSRIs work for depression,” Tyler Randall Black, a child and adolescent psychiatrist at British Columbia’s Children’s Hospital, told The Daily Beast. “There’s tons and tons of evidence that shows us they work, but not why they work.” McIntrye pointed out that we don’t even fully know how Tylenol works, despite the fact that it’s one of the most widely used painkillers in the world. Tylenol also has an unexpected impact on the brain – although it numbs social or psychological pain, that’s no reason to take it off the market.

Vilifying these medications can have unintended consequences because therapy is often unavailable, making SSRIs the only accessible option. “The demand for mental health care far exceeds the access available,” Sanacora said, adding that many Americans have to wait months to see a good cognitive behavioral therapist. In addition, 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 with The Daily Beast pointed to the serotonin hypothesis as a simple way to explain a complex disorder like depression, they pointed out that it has fostered downsides over time. The history of a “narrative of ‘chemical imbalance’ negatively influenced patients’ decision-making and self-understanding,” Awais Aftaib, a psychiatrist at Case Western Reserve University in Cleveland, Ohio, told The Daily Beast.

“The demand for mental health 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, leading those in the critical space of psychiatry to believe that it “empowers doctors and industry” over patients. Ironically, he ignores the millions of “experienced people” who have been helped by antidepressants.

Yet the million dollar question remains: how do SSRIs work? Aftaib explained that a new main hypothesis is that they encourage the creation of new neurons and new connections between neurons inside the brain. The hippocampus, a hippocampus-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 might work through different mechanisms in different individuals, so treatments might need to be more tailored on a case-by-case basis.

And more specific, individual treatments might require psychiatrists to be more honest with their patients about what we know and don’t know about these drugs, rather than giving an oversimplified (and downright inaccurate) explanation.

Black is already trying to do this with his patients: “I’m saying we know for sure it affects serotonin, but we don’t know how it changes your brain and we don’t know you’re low on serotonin to begin with.” He has found that these open discussions about what we know so far about therapy and medication pays off in the long run, and many of his patients will still choose to take the antidepressant as part of their search to find what suits them best.

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