Depression Isn’t Caused by a Chemical Imbalance

The prevailing theory for depression focuses on an alleged chemical imbalance in the brain—meta-researchers are now dispelling this narrative.

Our culture is saturated with pain-porn—immersive and emotionally gaudy displays of a person’s psychological turmoil—which too frequently make the author a beggar for praise, a performer asking others to admire their anguish. When done well, these “pain” pieces help to overcome stigmatization, to shed light on unspoken but not uncommon experiences (such as depression). Alternatively, and what happens more commonly, they reinforce victimhood as a virtue, as if keeping our wounds open heals others. We no longer reap many benefits from this genre.

When writing about a topic so personal as anxiety and depression, pointing out one’s own experience with it can help to quell quips from critics. It encourages us to open up to what the experts in their corner have to say. We can’t dismiss them with tired rebuttals, “You don’t understand. You’ve never been there! How dare you talk about this!” We act as if these statements free us from having to even consider the empirical evidence conducted by researchers and clinical practitioners.

Suffice it to say, during early adulthood I wrestled with what would be considered clinical depression and anxiety—scrupulosity to be specific—for several years. This period in my life included coming within seconds of a suicide attempt. My story isn’t all that unique. That’s the point. While individual anecdotes move us, creating resonance between one another, large-scale empirical inquiries provide firmer ground on which to stand.

The prevailing theory, particularly in pop culture, states that depression and anxiety are largely caused by chemical imbalances in the brain, and that by taking SSRIs, (Selective Serotonin Reuptake Inhibitors) like Zoloft, Paxil, or Prozac, we can be fixed. Our brains are broken. We are victims of our material bodies. If we have a malfunctioning cerebral organ that doesn’t manufacture the proper happiness chemicals, we can’t be blamed. We can’t truly be expected to experiment with other ways of improving our emotional well-being, not beyond swallowing a chalky pill, morning and night, for the rest of our lives. This explanation can be a powerful and relieving narrative for personal pain. It was for me, for a few years, until it became a burdensome belief, a broken story preventing me from taking responsibility for my emotional life.

If we have a malfunctioning cerebral organ that doesn’t manufacture the proper happiness chemicals, we can’t be blamed.

Once we embrace a story about our individual agony, we become militant in defending it. We worry that if we fiddle too much with the explanation that has kept our heads above water, that instead of finding a way to rise confidently above it, we will sink into the depths below. No doubt readers who currently hold to this justification for their depression are gearing up for a fight, ready to dismiss the alternative narrative that follows, but hear me out. I understand how frustrating it can feel, when in the throes of depression, to be told to “cheer up,” exercise, meditate, or hang out with friends—like these are magical prescriptions. I’m not saying that but rather seeking to discredit the story of pain that has kept many of us emotionally-crippled and disengaged with life. Hopefully, we can charter new water between the dangers of purely medical-material models for emotional health and the trite platitudes which misunderstand the complex suffering individuals encounter in their inner lives.   

Antidepressants Are More Like Placebos Than We Think

Of U.S. adults, 1 in 6 are on psychotropic drugs, with antidepressant use jumping by 65 percent from 1999 to 2014. We believe they work, but they don’t impact us the way we think they do.

In his recent book, Lost Connections: Uncovering the Real Causes of Depression—and the Unexpected Solutions (2018), Johann Hari points out, “When you give a patient a medical treatment, you are really giving her two things. You are giving her a drug, which will usually have a chemical effect on her body in some way. And you are giving her a story—about how the treatment will affect her.” Without a story or personal narrative accompanying, no placebo effect could be said to exist because the story is inextricable from the treatment (placebo effect being the power personal belief has in changing our physical and emotional health).

Extensive research has been conducted in the past two centuries showing the effects of placebos, such as Dr. John Haygarth’s experiment with a metallic wand at the turn of the 19th-century. Haygarth modeled it after the Perkins Tractor, a device that allegedly had some abilities to draw out illnesses. The company kept the actual properties of the wand proprietary and would run it over an ill person’s body, promising to heal them. As it turns out, this worked, resulting in some rather immediate and miraculous healings, including extreme cases of rheumatism. Haygarth and other physicians conducted similar experiments (with their own homemade wands of varied elements), producing similar results. Physicians couldn’t believe it. From a purely material perspective, these wands were phonies, but they had created physical results.

These days the public is well aware of placebo effects and understand that rigorous studies are done with control groups to ensure that antidepressants perform better than placebos before they’re allowed to go to market. Unfortunately, this isn’t entirely accurate.

In his book The Emperor’s New Drugs: Exploding the Antidepressant Myth (2009), Irving Kirsch conducts a meta-study of these experiments, using the Freedom of Information Act to access clinical trials previously withheld by drug companies to provide a more complete picture. Whenever a person takes a psychotropic drug, there is always a certain degree of placebo effect on top of the chemical result. To identify how much that effect is, a study must include a third control group. This is coincidentally rare, according to Kirsch, who says it’s like investigating a new remedy for colds. One group gets the remedy and the other gets the placebo. Most participants, if not all, get better over time. This third group helps control for which people will merely get better on their own, without external assistance.

Once we embrace a story about our individual agony, we become militant in defending it. We worry that if we fiddle too much with the explanation that has kept our heads above water, that instead of finding a way to rise confidently above it, we will sink into the depths below.

When Kirsch added up all the data from the publically available studies, he found 25 percent of the effects of antidepressants came from natural recovery, 50 percent resulted from the story participants had been told about antidepressants (placebo effect), and just 25 percent came from the actual chemicals. Furthermore, Kirsch found incomplete clinical studies conducted by many of these drug companies which were used to push their drugs to market. For example, Hari highlights, in his own book, that “in one trial for Prozac, the drug was given to 245 patients, but the drug company published the results for only twenty-seven of them. Those twenty-seven patients were the ones the drug seemed to work for.”  

Kirch’s work doesn’t completely negate the positive impact that antidepressants have on depression and anxiety, but to what degree do they actually help?

The Hamilton Scale is one way practitioners attempt to score the degree of one’s depression, ranging from 0 (pure bliss) to 51 (perfectly suicidal).  When he put the data from these clinical studies through the Hamilton Score, he found that antidepressants corresponded with an improvement of 1.8 points. To give this proper perspective, as Hari highlights, “You can get a six-point leap in your Hamilton score if you improve your sleeping patterns,” and that’s without all the side effects of psychotropic drugs—like weight gain, sexual dysfunction, fatigue, nausea, constipation, insomnia, and ironically, even anxiety and suicidal ideation.

This hurls a boulder into the narrative structure of those still clinging to the broken-brain explanation for their emotional affliction, and it hurts, especially the longer one has entrenched their psyche within this medical explanation. There is hope, but more deconstruction of that damaged (and damaging) story awaits.  

There’s No Such Thing As A Balanced or Imbalanced Brain

As with many great inventions, they’re stumbled upon as failed attempts to achieve something else. For example, Post-it Notes—paper with temporary re-adhering strips of glue—resulted from Dr. Spencer Silver’s blunderings with making a super-strong adhesive. In the 1950’s, patients with tuberculosis were given Marsilid. It did nothing to address tuberculosis, but it made people in the hospital ward noticeably joyful, expressively happy. Quickly it was being prescribed to depressed people, and soon psychotropic drugs proliferated.

When investigating the notion that depression is caused by low levels of serotonin, Hari consulted with Professor David Healy, a psychiatrist and scientist with over 200 peer-reviewed articles (and several books on pharmacology) to his name. Healy asserts, “There was never any basis for it, ever. It was just marketing copy. At the time the drugs came out in the early 1990s, you couldn’t get any decent expert to go on a platform and say, ‘Look, there’s a lowering of serotonin in the brains of people who are depressed’…There wasn’t any evidence for it.” He claims it hasn’t been discredited because “it didn’t ever get ‘credited,’ in a sense. There wasn’t ever a point in time when 50 percent of the field actually believed it.”

As it turns out, antidepressant drugs that increase serotonin do the same thing as drugs which reduce serotonin levels in the brain. These have the same effect as drugs which increase norepinephrine and dopamine, temporarily improving mood—in a minuscule way. So, no matter which neurochemical we manipulate, by increasing or decreasing it, they seem to produce similar outcomes. An individual is prescribed the drug and she experiences temporary elemental improvements in her mood, until her body adjusts to the chemical change and either a larger dosage or a different psychotropic concoction must be given to “balance the brain.” However, there’s no such thing as a balanced brain.

As it turns out, antidepressant drugs that increase serotonin do the same thing as drugs which reduce serotonin levels in the brain.

When pressed by Hari as to whether a “chemically balanced brain” exists, Professor Joanna Moncrieff, at University College of London, contends that the term doesn’t make sense. “There’s no evidence that there’s a chemical imbalance” in individuals with depression or anxiety. Hari discusses the issue with clinical psychologist Dr. Lucy Johnstone, who declares the serotonin theory “is a lie. I don’t we think we should dress it up and say, ‘Oh, well, maybe there’s evidence to support that.’ There isn’t.”

Has the Science Been Wrong About Depression?

These falsehoods are maintained in the mainstream, largely because of two phenomena: publication bias and regulatory capture. Companies are oriented toward profit, but poorly-run businesses bias themselves toward short-sighted means of making profit. They want clinical trials proving their product works, that their new drug can alleviate depression and anxiety. This isn’t to fall into the lazy-thinking surrounding the refrain: “big pharma is evil.” Rather, individuals in the pharmaceutical industry are not inherently more wicked than the rest of us, but they do face a culture problem. If the leadership in these companies don’t encourage strategies focused on adding long-term value to the lives of consumers—if a company is found to be dishonest or not practicing due diligence, they may gain some customers now, but they’ll lose them in the long-run—they’ll get stuck in the trap of publication bias. These companies focus too much on finding studies that confirm that their drugs work, when in reality they should be testing out ways to prove that they don’t. Given the immense cost of clinical studies, few incentives exist to take the latter approach, and so we continue down this road of empirically invalid psychotropic drugs.

These falsehoods are maintained in the mainstream, largely because of two phenomena: publication bias and regulatory capture.

Furthermore, government agencies believed to regulate against this, to protect consumers, become extensions of large corporations—regulatory capture. This form of government failure means “captured agencies” prioritize the interests of specific lobbying groups (pharmaceutical companies) rather than the general public (or even the scientific community).  

In his iconoclastic 2010 article “Lies, Damned Lies, and Medical Statistics,” David H. Freeman introduces us to John Ioannidis, a meta-researcher who has made a career of keeping his colleagues in the medical community honest. Ioannidis claims nearly 90 percent of the published information that medical professionals rely on is flawed. Freeman notes that, fortunately, Ioannidis’ “work has been widely accepted by the medical community; it has been published in the field’s top journals, where it is heavily cited; and he is a big draw at conferences.”

Still, Ioannidis holds the same fears researchers in any field do, including pharmaceutical scientists; will he be able to secure funding? He says this obsession with winning funding has gone a long way in weakening the validity of medical research. Like Kirsch, Ioannidis and his team discovered that “widely prescribed antidepressants such as Prozac, Zoloft, and Paxil were revealed to be no more effective than a placebo for most cases of depression.”

Short-sighted strategies encouraged by pharmaceutical companies eager to validate their drugs merely amplify pressure placed on researchers looking for funding. Ioannidis bemoans, “The studies were biased… Sometimes they were overtly biased. Sometimes it was difficult to see the bias, but it was there. At every step in the process, there is room to distort results, a way to make a stronger claim or to select what is going to be concluded.” All things relatively equal, if one interpretation of the data will secure further funding and the other will not, it’s little wonder so many flawed studies are published. The current regulatory apparatus makes this worse. Johann Hari draws attention to the fact that 40 percent of the regulators’ wages in the US are paid by drug companies (the case in Great Britain is 100 percent).

Widely prescribed antidepressants such as Prozac, Zoloft, and Paxil were revealed to be no more effective than a placebo for most cases of depression.

Scientific inquiry cannot prove anything, but rather can only disprove. From a deeply philosophical (and, thus scientific) perspective, there is always room for doubt, even if that means a claim is 99% certain. Science is in constant flux, impermanent, a set of temporary claims. Recall the current replication crisis plaguing the social science world, where two-thirds of psychology studies can’t be replicated in other labs. Fortunately, to address this and the high costs of conducting studies, some research institutions are encouraging scientists to publish fewer but more rigorous studies.

This is where much of the research went wrong. We owe a great debt to meta-researchers, like John Ioannidis and Irving Kirsch, who preserve the integrity of the scientific method and, admiringly, caution us against limiting narratives about our emotional torment. It’s possible that a significant chemical basis for emotional health exists, but the scientific proof for it just isn’t there.

Where Do We Go From Here?

The evidence stands, yet some of us resist. We refuse to understand our depression in non-material frames, for these new constructs imply that we have a greater degree of power we can exert on our emotional health (even by rewiring our brains.) In essence, nobody chooses depression or anxiety, just like we don’t choose lung cancer or to break our leg when we fall from a tall tree. However, we can investigate those parts of our worldview or lifestyle—the things we do choose—uncovering that which provides emotional resiliency and spiritual buoyancy.  

This means addressing our individual ways of being in the world. Our choices and interpretative frameworks for what happens in the phenomenal realm are more culpable than neurochemicals in our brains. Leaving behind this failed narrative about brain chemistry allows us to consider other solutions, assemblages which house the locus of control firmly within the individual. (My intention here is not to elucidate upon possible routes of healing but to warn against the predominant one, which is likely a dead end.)

Scientific inquiry, incomplete but far-reaching, contributed to broken explanations that held us bound, but thankfully, we have a new liberation, and for that, the scientific endeavor must also to be celebrated.

  1. […] depression in the United States, where 1 in 6 adults are prescribed psychotropic drugs, have been on the rise for the past few decades. Antidepressant use jumped by 65 percent from 1999 to 2014. Among adolescent girls, depression […]

    Reply

Leave a Reply