Some 2,000 years ago, the Ancient Greek scholar Hippocrates argued that all ailments, including mental illnesses such as melancholia, could be explained by imbalances in the four bodily fluids, or “humors.” Today, most of us like to think we know better: Depression—our term for melancholia—is caused by an imbalance, sure, but a chemical imbalance, in the brain.
It blew my mind to read this article about the History of Prozac, and to be honest, it pissed me off. I struggled with depression for years, and started seeing a therapist regularly when I was seventeen. For seven years she would listen to me patiently before saying, “You know, we could try the drugs…”
This explanation, widely cited as empirical truth, is false. It was once a tentatively-posed hypothesis in the sciences, but no evidence for it has been found, and so it has been discarded by physicians and researchers. Yet the idea of chemical imbalances has remained stubbornly embedded in the public understanding of depression.
When I was seventeen, most of my friends who were depressed were trying “the drugs,” and it was not going well. The side effects seemed horrific, making them “feel better” by putting them in a zombie like state. I’m simplifying, I know, but when I was seventeen, I didn’t want to try “the drugs,” and I maintained that stance for seven years.
The theory of chemical imbalances was a neat way of explaining just how brain malfunctions could cause mental illness. It was first hypothesized by scientists in academic papers in the mid-to-late 1960s, after the seeming early success of drugs thought to adjust chemicals in the brain. Though the evidence never materialized, it became a popular theory and was repeated so often it became accepted truth.
But when you’re twenty-four and you haven’t graduated college and you can’t keep a steady job or a girlfriend and you live in a dirty, filthy one-bedroom apartment with three cats getting high as much as you can, you might change your mind. You might be running out of ideas and options; you might be desperate enough to fix this that maybe it’s time to try.
It’s not hard to see why the theory caught on: It suited psychiatrists’ newfound attempt to create a system of mental health that mirrored diagnostic models used in other fields of medicine. The focus on a clear biological cause for depression gave practicing physicians an easily understandable theory to tell patients about how their disease was being treated.
So I tried. For four years, I tried. I tried tricyclics and SSRIs. I would take a drug for several months to learn if it would work, what it would do to me. I would end up taking a cocktail, a mix of different drugs that were playing against each other, trying to neutralize the side-effects. The main problem would end up being sleep. My already tenuous relationship to a regular sleep cycle was scrambled. It all culminated with me breaking down completely, exhausted after being awake for three straight days.
“[T]he serotonin hypothesis is typically presented as a collective scientific belief,” write Lacasse and Leo, though, as they note: “There is not a single peer-reviewed article that can be accurately cited to directly support claims of serotonin deficiency in any mental disorder, while there are many articles that present counterevidence.”
Despite the lack of evidence, the theory has saturated society. In their 2007 paper, Lacasse and Leo point to dozens of articles in mainstream publications that refer to chemical imbalances as the unquestioned cause of depression. One New York Times article on Joseph Schildkraut, the psychiatrist who first put forward the theory in 1965, states that his hypothesis “proved to be right.” When Lacasse and Leo asked the reporter for evidence to support this unfounded claim, they did not get a response. A decade on, there are still dozens of articles published every month in which depression is unquestionably described as the result of a chemical imbalance, and many people explain their own symptoms by referring to the myth.
When I woke up after finally crashing, I stopped trying. I stopped taking the drugs, and stopped going to therapy. I started finding my own way, and stumbled through the dark in the wilderness for many years.
Meanwhile, 30 years after Prozac was released, rates of depression are higher than ever.
Depression, according to current studies, has an estimated heritability of around 37%, so genetics and biology certainly play a significant role. Brain activity corresponds with experiences of depression, just as it corresponds with all mental experiences. This, says Horwitz, “has been known for thousands of years.” Beyond that, knowledge is precarious. “Neuroscientists don’t have a good way of separating when brains are functioning normally or abnormally,” says Horwitz.
If depression was a simple matter of adjusting serotonin levels, SSRIs should work immediately, rather than taking weeks to have an effect. Reducing serotonin levels in the brain should create a state of depression, when research has found that this isn’t the case. One drug, tianeptine (a non-SSRI sold under the brand names Stablon and Coaxil across Europe, South America, and Asia, though not the UK or US), has the opposite effect of most antidepressants and decreases levels of serotonin.
This doesn’t mean that antidepressants that affect levels of serotonin definitively don’t work—it simply means that we don’t know if they’re affecting the root cause of depression. A drug’s effect on serotonin could be a relatively inconsequential side effect, rather than the crucial treatment.
The work of Irving Kirsch, associate director of the Program in Placebo Studies at Harvard Medical School, including several meta-analyses of the trials of all approved antidepressants, makes a compelling case that there’s very little difference between antidepressants and placebos. “They’re slightly more effective than placebo. The difference is so small, it’s not of any clinical importance,” he says. Kirsch advocates non-drug-based treatments for depression. Studies show that while drugs and therapy are similarly effective in the short-term, in the long-term those who don’t take medication seem to do better and have a lower risk of relapse.