chemical has been so universally accepted that no one bothers to question it or even research it using modern rigors of science. According to Dr. Joanna Moncrieff, we have been led to believe that these medications have disease-based effects—that they’re actually fixing, curing, correcting a real disease in human physiology. Six decades of study, however, have revealed conflicting, confusing, and inconclusive data.17 That’s right: there has never been a human study that successfully links low serotonin levels and depression. Imaging studies, blood and urine tests, postmortem suicide assessments, and even animal research have never validated the link between neurotransmitter levels and depression.18 In other words, the serotonin theory of depression is a total myth that has been unjustly supported by the manipulation of data. Much to the contrary, high serotonin levels have been linked to a range of problems, including schizophrenia and autism.19
Paul Andrews, an assistant professor of psychology, neuroscience, and behavior at McMaster University in Canada, is among the vocal experts challenging the traditional depression model. In a 2015 review, he declares that the science behind antidepressant medications appears to be backward: serotonin is a downer, not an upper.20 He argues that serotonin is almost like a first responder to stress. When our bodies are under duress, serotonin helps to reallocate resources at a cellular level. This further shows that we really have no idea what’s going on when it comes to looking at one simple chemical. Andrews brings up a good point in a recent review: we can’t measure serotonin in a living human brain yet, so it’s impossible to know exactly how the brain is releasing and using serotonin. What scientists must do instead is rely on evidence about levels of serotonin that the brain has already metabolized, and by studying seratonin in animal models. To date, the best available evidence indicates that more serotonin—not less—is released and used during depressive episodes. This natural surge of serotonin helps the brain adapt to depression; it forces the body to spend more energy on conscious thought than to areas such as growth, development, reproduction, immune function, and the stress response.21
Andrews also happens to be an evolutionary psychologist, and has asserted in previous research that antidepressants leave individuals worse off after they stop taking them. He agrees that even though depression can be a painful, troubling experience, most forms of depression are normal adaptations to stress. According to Andrews, when patients on SSRI medication improve, it appears that their brains are actually overcoming the effects of antidepressants, rather than being helped by them. The drugs are interfering with the brain’s own mechanisms of recovery. This is an important point, because time and time again people ask me how antidepressants appear to be helpful in the short term. Perhaps, in the rare instance that their effects are adaptive, it is by virtue of the brain’s own powers trying to combat the assault of the antidepressants—not the other way around. But over time, as the assault continues, the brain is functionally compromised under the constant force of the incoming drugs.
One critical review of the serotonin hypothesis concludes: “ . . . there is no direct evidence of serotonin or norepinephrine deficiency despite thousands of studies that have attempted to validate this notion.”22 And in a scathing review on major depression published in the New England Journal of Medicine in 2008, the researchers write: “. . . numerous studies of norepinephrine and serotonin metabolites in plasma, urine, and cerebrospinal fluid as well as postmortem studies of the brains of patients with depression, have yet to identify the purported deficiency reliably.”23
In the cogent words of Dr. Daniel Carlat, author of Unhinged, “We have convinced ourselves that we have developed cures for mental illnesses . . . when in fact we know so little about the underlying neurobiology of their causes that our treatments are often a series of trials and errors.”24 Indeed, the brain orchestrates a delicate interplay among some one hundred neurotransmitters, including fourteen different types of serotonin receptors. To think we can cherry-pick one brain chemical and cure all and every behavioral disturbance is a gross oversimplification and downright absurd.
The brain is much more complex than the serotonin model can describe. To be clear, SSRIs block the removal of serotonin from the junctions between nerve cells (synapses) in the brain so there’s increased firing of serotonin nerves. But when serotonergic nerves are overstimulated, they become less sensitive in a bid to establish equilibrium again. In science speak this is called downregulation. And such downregulation doesn’t return to normal after the drug is stopped. We in the scientific community still don’t know if the downregulation can become permanent, but a cadre of my colleagues and I believe this poses a serious risk to the brain. It’s no surprise to me that in the first twelve years after its initial marketing blitz, Prozac was named in more than 40,000 reports of adverse effects submitted to the FDA.25 No other drug comes close to such a history.
Even if we accepted the proposition that these drugs are helpful for some people, extrapolating a medical cause from this observation would be akin to saying that shyness is caused by a deficiency of alcohol, or that headaches are caused by a lack of codeine. And what about a genetic vulnerability? Is there such thing as a depression gene? In 2003, a study published in Science suggested that those with genetic variation in their serotonin transporter were three times more likely to be depressed.26 But six years later this idea was wiped out by a meta-analysis of 14,000 patients published in the Journal of the American Medical Association that denied such an association.27 Dr. Thomas Insel, director of the National Institute of Mental Health, commented with the following: “Despite high expectations, neither genomics nor imaging has yet impacted the diagnosis or treatment of the 45 million Americans with serious or moderate mental illness each year.”28 Dr. Carlat speaks the truth in his own words: “And where there is a scientific vacuum, drug companies are happy to insert a marketing message and call it science. As a result, psychiatry has become a proving ground for outrageous manipulations of science in the service of profit.”29
Suffice it to say the data has poked so many holes in the serotonin theory that even the field of psychiatry itself is putting down its sword. In a 2005 essay for PLOS Medicine by Drs. Jeffrey R. Lacasse and Jonathan Leo, the authors gathered sentiments from influential thinkers in the field, including conventional clinicians and researchers who have expressed doubt on the entirety of what psychiatry has to offer around antidepressants (see tables on the following pages).30
The medical-pharmaceutical complex has constructed quite a few houses of cards, and far too many of its treatments—very profitable treatments—are offered without solid evidence to support doing so. In fact, only two studies are required for FDA licensure of most pharmaceuticals, essentially leaving the population to participate in a post-marketing experiment in which adverse effects—causalities—are monitored passively. It’s a fabrication of science to think these drugs have a place in medicine, what is meant to be the art of healing. It could be argued that antidepressants are the new tobacco, and, like the tobacco industry, Big Pharma can wield a lot of power through clever marketing to seduce and influence us in stealthy, seemingly benign ways that are anything but.
DIRECT-TO-CONSUMER ADVERTISING
Sadly, direct-to-consumer advertising (DTCA) in America has allowed pharmaceutical companies to “teach” the public about brain chemical imbalances and serotonin deficiencies via sound bites and cleverly worded taglines that escape FDA policing. I have patients who come in believing that the solution is in a pill—what they’ve learned essentially from commercials. It’s been calculated that DTCA advertising is responsible for nearly half (49 percent) of requests for drugs.31 And fully seven out of ten times doctors prescribe based on appeals made by patients who learned through their computers and televisions that they have an “imbalance” that must be fixed with a pill.32
“Antidepressants and the Chemical Imbalance Theory of Depression: A Reflection and Update on the Discourse,” Behavior Therapist 38, no. 7 (October 2015): 206–213.
