A Mind of Your Own: The Truth About Depression and How Women Can Heal Their Bodies to Reclaim Their Lives

The predominant theory behind modern antidepressants (SSRIs, or selective serotonin reuptake inhibitors) is that they work by increasing the availability of serotonin, a neurotransmitter famously associated with mood, in the gaps between cells of the brain. In fact, if you were to quiz someone on the street about the biology of depression, they would likely parrot “chemical imbalance” in the brain and go so far as to say a “serotonin deficiency.” This hypothesis, referred to as the monoamine hypothesis, grew primarily out of two main observations made in the 1950s and ’60s.

One was seen in patients being treated for tuberculosis who experienced mood-related side effects from the anti­tubercular drug iproniazid, which can change the levels of serotonin in the brain. Another was the claim that reserpine, a medication introduced for seizures and high blood pressure, depleted these chemicals and caused depression—­that is, until there was a fifty-four person study that demonstrated that it resolved depression.

From these preliminary and largely inconsistent observations a theory was born, crystallized by the work and writings of the late Dr. Joseph Schildkraut, who threw fairy dust into the field in 1965 with his speculative manifesto “The Catecholamine Hypothesis of Affective Disorders.”

Dr. Schildkraut was a prominent psychiatrist at Harvard who studied catecholamines, a class of naturally occurring compounds that act as chemical messengers, or neurotransmitters, within the brain. He looked at one neurochemical in particular, norepinephrine, in ­people before and during treatment with antidepressants and found that depression suppressed its effectiveness as a chemical messenger. Based on his findings, he theorized broadly about the biochemical underpinnings of mental illnesses. In a field struggling to establish legitimacy (beyond the therapeutic lobotomy!), psychiatry was desperate for a rebranding, and the pharmaceutical industry was all too happy to partner in the effort.

This idea that these medications correct an imbalance that has something to do with a brain 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.

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.

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.

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.

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.

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.”

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.”

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.”

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.

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.

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.

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.”

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.”

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).

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.

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.

“Antidepressants and the Chemical Imbalance Theory of Depression: A Reflection and Update on the Discourse,” Behavior Therapist 38, no. 7 (October 2015): 206–213. Reprinted with permission.

In the ten-year period between 1999 and 2008, DTCA tripled, from $1.3 to $4.8 billion, their efforts at educating patients about their need for psychiatric medication. The modern drug business has been built on “brain” medicines. Valium was the first blockbuster, selling 2 billion tablets in 1978. Then in the 1990s came Prozac, which defined the industry. The pharmaceutical industry spent $4.53 billion on direct-to-consumer advertising in the United States alone in 2014, up 18 percent from the previous year.

The flagrant disconnect between the advertisements and scientific literature has been written about for more than a decade now, but you probably haven’t read about it. It was clearly stated by Drs. Lacasse and Leo in their 2005 paper: “These advertisements present a seductive concept, and the fact that patients are now presenting with a self-described ‘chemical imbalance’ shows that the [advertising] is having its intended effect: the medical marketplace is being shaped in a way that is advantageous to the pharmaceutical companies.”

As far back as 1998, at the dawn of consumer advertising of SSRIs, Professor Emeritus of Psychology and Neuroscience Elliot Valenstein of the University of Michigan summarized the scientific data by concluding, “What physicians and the public are reading about mental illness is by no means a neutral reflection of all the information that is available.”

The United States and New Zealand are the only countries in the world that allow advertisement on television for prescription drugs. In 1997, a change to an FDA regulation opened the floodgates on direct-to-consumer advertising, allowing drug makers to promote their wares on television. This also paved the way for celebrities, athletes, models, and aging baby boomers to dominate those ads.

Given these forces, along with the number of symptoms listed under antidepressant use, it’s really no surprise that more than $11 billion is spent each year on these medications.

Pharmaceutical companies have more than six hundred lobbyists, and they finance more than 70 percent of FDA trials.

They court physicians, toss them copious free samples, pay consultants to speak at scientific meetings, advertise in medical journals, fund medical education, and ghostwrite, selectively choosing and redundantly submitting data for publication. Psychiatric studies funded by Big Pharma are four times more likely to be published if they report positive results. Only 18 percent of psychiatrists disclose their conflicts of interest when they publish data.

Their studies allow for all kinds of indiscretions, such as removing ­people who are likely to respond to placebo before the study to strengthen the perceived benefit and using sedative medications with the study’s medications, thereby skewing results in favor of the drug (more on this shortly).

A now famous 2008 study in the New England Journal of Medicine led by Dr. Erick Turner at Portland VA Medical Centers sought to expose the extent of data manipulation.

Through valiant efforts to uncover unpublished data, he and his team determined that from 1987 to 2004, twelve antidepressants were approved based on seventy-four studies; thirty-eight were positive, and thirty-seven of these were published. Thirty-six were negative (showing no benefit), and three of these were published as such, while eleven were published with a positive spin (always read the data, not the author’s conclusion!), and twenty-two were unpublished.

The FDA requires only two studies for drug approval, so you can see how these companies are tossing the coin over and over again until heads comes up and hoping no one is looking when it’s tails. To get a sense of just how misleading the pharmaceutical industry can be, consider the largest study to date funded by the National Institute of Mental Health, conducted at the University of Texas in 2006.

It cost the public $35 million for researchers to follow more than four thousand patients who were treated with Celexa over twelve months. This was not a double-blind placebo controlled study, so the ­people knew what they were getting. Half of them reportedly improved at eight weeks. Those who didn’t were switched to Wellbutrin, Effexor, or Zoloft or “augmented” with Buspar or Wellbutrin. Guess what? It didn’t matter who took what, because the same percentage of the group allegedly improved (18 to 30 percent) no matter what drug they were on. Only 3 percent of patients were supposedly in remission at twelve months. Now here’s where the story gets interesting.

In February 2012, a suit was filed against Celexa’s maker, Forest Pharmaceuticals, alleging that the company paid a bribe to the principal investigator of this particular study to fix the results in favor of Celexa.

The suit was settled out of court, and it came on the heels of the company having to pay a criminal fine of $150 million and forfeit assets of $14 million for suppressing and misrepresenting data on the negative effects of using their drug to treat adolescents. Celexa was only approved to treat adults, but in pursuit of selling more drugs and increasing profits, the company targeted doctors who treated children and teens.

It’s a foregone conclusion: these practices sabotage the accuracy of data and convey information that corrupts a doctor’s delivery of care and endangers patients. The tragic cost of this data manipulation is the loss of true informed consent. Physicians cannot adequately share with their patients the risks and benefits if the benefits are fabricated and the risks are not uncovered or are unacknowledged. What’s more, these drugs are no more effective than a placebo. As far back as 1984, the National Institute of Mental Health was quoted as saying: “Elevations or decrements in the functioning of serotonergic systems per se are not likely to be associated with depression.” The good old placebo effect likely explains any perceived short-term effects from the antidepressants.

SHORT-TERM EFFICACY: THE POWER OF THE PLACEBO EFFECT

Despite Big Pharma’s efforts, the truth about these brain bombs is emerging. In 1998, the year direct-to-consumer advertising took off, Harvard psychologist and researcher Dr. Irving Kirsch, an established and respected expert on the placebo effect, published a landmark meta-analysis of nearly three thousand patients who were treated with antidepressants, psychotherapy, placebo, or no treatment.

The results of the study became front-page news and received widespread attention—­and criticism. Kirsch found that placebo duplicated 75 percent of the drug’s effect, that non-antidepressant medications had the same effect as antidepressants, and that the remaining 25 percent of the apparent drug effect was attributable to what’s called the “active placebo effect.”

Kirsch uses this term to refer to the effect of the mere belief in antidepressants—­a belief that is triggered by the experience of side effects such as nausea, headache, and dry mouth. What happens in a trial is that subjects are put in either the placebo group or the medication group without knowing which group they were assigned to. Because the placebo is without side effects (an inactive placebo), when they develop side effects, all of those commercial-inspired beliefs about their brain’s chemical correction are kicked into high gear, and at least a quarter of these ­people begin feeling better because of it.

So how much can we thank the placebo effect when we experience fewer symptoms while taking an antidepressant? The backlash to Kirsch’s study inspired him to continue exploring the power of the placebo. By 2008 he’d published another compelling meta-analysis study that further stirred up an incendiary response from critics.

This time he leveraged the Freedom of Information Act to access unpublished studies and found that when these unpublished studies were included, antidepressants outperformed placebo in only twenty of forty-six trials. That’s less than half! What’s more, the overall difference between drugs and placebos was 1.7 points on the 52-point Hamilton Rating Scale for Depression, used to rate depression in clinical research. Put simply, this small increment is clinically insignificant, and likely accounted for by minor side effects (such as activation and sedation).

The response to this publication led Kirsch to come out with another paper that clearly laid out the facts, counterchallenged his critics, and further demonstrated the power of the placebo.

In his concluding thoughts, he writes: “Without accurate knowledge, patients and physicians cannot make informed treatment decisions, researchers will be asking the wrong questions, and policymakers will be implementing misinformed policies. If the antidepressant effect is largely a placebo effect, it is important that we know this. It means that improvement can be obtained without reliance on addictive drugs with potentially serious side effects.”

When Kirsch’s book The Emperor’s New Drugs: Exploding the Antidepressant Myth came out in 2010 with proof that antidepressants do not have a clinically meaningful advantage over placebo, his analysis was acknowledged by researchers as a valid albeit provocative contribution to medical literature. But it didn’t change clinical psychiatry or the number of antidepressants prescribed, and it continued to incur the criticism and even rage of prescribing psychiatrists desperate to pick apart his findings to defend their now baseless practices. It’s hard to blame them—­they put a lot of time, money, and effort into learning mistruths around antidepressants! The irony in Kirsch’s findings is that the results came from studies that were underwritten and designed by the drug companies themselves. These studies were conducted in a way that would give the drugs an advantage, yet they still didn’t outperform the placebo.