Do you know what causes depression? Many people would respond that it’s due to a chemical imbalance in the brain. This chemical imbalance theory has been widely promoted by drug companies and psychiatrists alike, to the extent that it’s accepted as fact. The glaring problem is that the chemical imbalance theory is just that — a theory — and worse still, it’s a theory that has been largely discredited.

The theory was first proposed by scientists in the 1960s after it appeared certain antidepressant drugs worked by altering brain chemicals, but it was stated that “the findings are inconclusive.”¹ Yet, the theory was proposed at a time when treating mental illness via psychoanalysis was falling out of favor while viewing it as tied to a physical or biological mechanism was in vogue.

The idea quickly spread, becoming the medical dogma for depression, despite concrete evidence proving its worth. “The fact that practicing physicians and leaders of science bought that idea, to me, is so disturbing,” Steve Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard, told Quartz.² The news outlet continued:

“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.”³

Prozac, Zoloft Bring Chemical Imbalance Theory for Depression to the Mainstream

The release of the antidepressant Prozac (fluoxetine) in the late 1980s was a game changer for depression treatment in that the drug’s maker, Eli Lilly, heavily promoted the chemical balance theory as a marketing gimmick to sell the drug. With fewer side effects than some of the earlier antidepressants, Prozac became a blockbuster drug and the poster child for the selective serotonin reuptake inhibitor (SSRI) class of antidepressants, which target the neurotransmitter serotonin.

“There was, of course, no demonstrable evidence showing that depressed patients had any imbalance, but Lilly ran with it,” Psychology Today noted. “Before long, psychiatrists and psychiatric patients alike came to identify with the idea that mental disorders are caused by chemical imbalances in the brain.”⁴

Zoloft (sertraline), another SSRI, was another major player in spreading and perpetuating the chemical balance theory, with their television ads going so far as to say, “While the causes are unknown, depression may be related to an imbalance of natural chemicals between nerve cells in the brain. Prescription Zoloft works to correct this imbalance.”⁵

It’s important to note that in the time since Prozac flooded the market, depression still remains poorly treated, despite a plethora of new antidepressant options to choose from. SSRIs work by preventing the reuptake (movement back into the nerve endings) of the neurotransmitter serotonin.

This makes more serotonin available for use in your brain, which is thought to improve your mood since low serotonin levels are said to lead to depression. Yet, as written in the Handbook of Experimental Pharmacology, it’s a largely disproven theory:⁶

“Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by the drug companies reveal that most (if not all) of the benefits are due to the placebo effect.

Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin … The serotonin theory is as close to any theory in the history of science having been proved wrong.”

Harvard: Depression ‘More Complex’ Than a Brain Chemical Imbalance

It’s quite possible that people who are depressed may have an imbalance of certain chemicals in their brain. But to speculate that that imbalance is the cause of their symptoms is overly simplistic. For instance, it’s known that psychological stress can cause biological changes in the brain, including a reduction in the size of the hippocampus, which is used for learning and memory.⁷ In turn, it’s known that some people with depression have a smaller-than-average hippocampus.⁸

“Evidence of biological changes correlating with environmental stressors is vastly different from evidence that mental illnesses are ‘caused’ by biological deficits,” scientists wrote in a 2008 report on the chemical imbalance theory,⁹ and this is an important point. Even Harvard Medical School acknowledges that while brain chemicals may play a role in your mood, it is not accurate to suggest that one being too high or too low is at the root of depression. They state:¹⁰

“Research suggests that depression doesn’t spring from simply having too much or too little of certain brain chemicals. Rather, there are many possible causes of depression, including faulty mood regulation by the brain, genetic vulnerability, stressful life events, medications, and medical problems.

It’s believed that several of these forces interact to bring on depression … There are millions, even billions, of chemical reactions that make up the dynamic system that is responsible for your mood, perceptions, and how you experience life.”

One theory posits, for instance, that stress could be a major contributor to depression because it suppresses the production of new neurons in the hippocampus. In order to feel better, people with depression may need to increase neurogenesis (the generation of new neurons), which takes weeks.

This would explain why many people who take antidepressants don’t notice any improvement for several weeks.¹¹ If the action was really on neurotransmitters, the patient should feel better right away when levels increase. Instead, triggering the growth of neurons could be the secret, which is a process that can be triggered naturally via exercise.