Go Ad-Free
logoThe People's Perspective on Medicine

Debunking the Chemical Imbalance Theory of Depression

Why has the chemical imbalance theory of depression and other mental illnesses lasted so long? What does the latest research reveal?

First, a confession. I got my start in research by working in a neuropharmacology laboratory at the New Jersey Neuropsychiatric Institute. My mentors were Carl Pfeiffer, MD, and Leonide Goldstein, DSc. They were giants in the field of neuroscience and taught me a great deal about mental illness and the brain. I embraced the chemical imbalance theory of mental illness because my mentors believed it. It was based on the idea that if we just tinkered with the chemical soup in the brain, we might be able to “cure” depression, insomnia, anxiety, schizophrenia, bipolar disorder and other forms of mental distress. It was a giant experiment that did not turn out as expected.

A VERY Short History of Mental Illness During the 20th Century:

I started working at the NJ. Neuropsychiatric Institute in 1967, just around the time the idea of deinstitutionalization took hold. In the mid-1950s it is estimated that nearly 600,000 patients were hospitalized in the US with a diagnosis of mental illness (Center for Court Innovation, 2001). Many of those state mental institutions were grim places. They did, however, provide food, clothing, housing and a modicum of treatment.

They were also expensive to operate. It’s no wonder that many states embraced the idea of the “revolving door” or a “de-institutionalization” policy starting in the 1960s. With the arrival of new antipsychotic medications for schizophrenia and antidepressants for depression, states started making it harder to commit people to psychiatric hospitals.

By 1999 the population in mental hospitals had dropped to under 80,000 (Prison Madness, Terry Kupers). That may seem in retrospect like a good thing, but community-based treatment never really got off the ground.

The theory was that new psychiatric medicines would revolutionize the treatment of mental illness. States were supposed to provide access to meds, housing, jobs, out-patient therapy and other treatment services. Instead, though, many mentally ill people ended up on the streets homeless and without adequate access to care.

The jail population exploded and became “hospitals of last resort.” Many prisoners have severe mental illnesses and are not getting appropriate treatment. This process has been called “transinstitutionalization.” The chemical imbalance theory of mental illness may not have caused the shift, but it certainly sped the changes in policy.

The Chemical Imbalance Theory Of Mental Illness Caught On:

The idea that mental illness is the result of a chemical imbalance led to the concept of a quick fix. Just tinker with the neurochemicals and patients with anxiety, depression, obsessive compulsive disorder (OCD) or schizophrenia could be “fixed.” Once on the right “cocktail” of neurochemicals, they would no longer need talking therapy. This made it relatively easy for states to justify cutting back on their pricey psychiatric hospitals.

The result: many patients ended up on the street and/or in prison. Police departments are ill equipped to handle psychotic or suicidal individuals. And jails or prisons just make the whole situation worse. The drugs that were supposed to correct the chemical imbalances of mental illness have not worked well for many disturbed people.

Antidepressants Are Hugely Popular:

Drugs for depression are extremely popular. According to the Centers for Disease Control and Prevention, one in five middle-aged women takes an antidepressant. For women over the age of 60, the CDC says that rate is one in four.

At last count, over 200 million prescriptions were dispensed for drugs like sertraline, bupropion, escitalopram, fluoxetine and duloxetine each year. Multiply that number by 30 pills per bottle and you end up with more than 6 billion tablets and capsules.

The Chemical Imbalance Theory of Depression:

For decades, many neuroscientists believed that people suffering from depression had a chemical imbalance in their brains. It hasn’t just been researchers, though. Clinicians and patients alike have also adopted this idea.

According to Psychology Today (July 19, 2022):

“Surveys indicate that 85-90 percent of the public believes low serotonin or a chemical imbalance causes depression.”

Perhaps this is due in part to the popularity of SSRI medications like fluoxetine (Prozac), sertraline (Zoloft) and paroxetine (Paxil). SSRI stands for selective serotonin re-uptake inhibitors. These drugs and their chemical cousins, the serotonin-norepinephrine re-uptake inhibitors such as venlafaxine (Effexor) or duloxetine (Cymbalta), are thought to work by increasing levels of neurotransmitters at critical brain junctions.

This mechanism certainly sounds plausible, if not entirely nuanced. And a good explanation for why something works is often very convincing.

Some People May Have a Chemical Imbalance:

We suspect that some people may in fact have some sort of neurochemical imbalance. We have heard from individuals who tell us that as soon as they started taking an antidepressant drug, their lives changed dramatically for the better.

Some describe this as having a veil removed from their heads. For them, life goes from dull gray and/or flat to colored and textured. Medications can make a huge difference for such individuals.

The Chemical Imbalance Theory Does Not Hold For Everyone:

Over the last few decades, though, scientists have been raising questions about the serotonin hypothesis of depression. First, some researchers have pointed out that antidepressants are not nearly as effective as they initially seemed.

An analysis of more than 200 randomized controlled trials found that only about 15 percent of study participants got significant antidepressant benefit beyond the placebo response (BMJ, Aug. 2, 2022). While that certainly could be important for some depressed patients, it is hardly an earth-shaking response.

And that may be an optimistic statistic. You may want to read this article on our website: “Balancing the Benefits and Risks of Antidepressants” written by Dr. Amy Beausang. She describes other studies that suggest antidepressants are barely better than placebos. Scientists have conducted few studies over long periods of time, even though patients are often prescribed such drugs for years.

Second, investigators have looked for evidence that low serotonin levels are actually the root cause of depression. A recent review of 17 studies gave this question close attention (Molecular Psychiatry, July 20, 2022).

Despite analyses of body fluids and genetics, the researchers concluded:

“The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.”

Rethinking the Chemical Imbalance Theory of Depression:

In other words, we probably need to re-think our assumptions that a drug like fluoxetine can correct a chemical imbalance in the brain and make depression disappear. Depression is real and causes a great deal of suffering, but it is complex.

Most likely there are numerous factors determining whether a person suffers depression. As a result, there may be many paths to alleviating suffering, including exercise, talk therapy, acupuncture and cognitive behavioral therapy, among others. And some people do benefit greatly from medication.

To learn more about this controversial topic, take a few minutes to listen to our recent interview:

Show 1315: Are We Medicating Normal Emotions?
A psychiatrist and a patient each describes her perspective on the dangers of medicating normal emotions with psychotropic drugs.

You can stream the audio podcast by clicking on the white arrow in the green circle under the photograph of Dr. Anna Lembke. The other option is to download the mp3 file by clicking on the link at the bottom of the page.

What Do You Think?

Please share your thoughts about the chemical imbalance theory of mental illness in the comment section below. If you believe this article is worth sharing with friends and/or family, please scroll to the top of the page and click on the link to email, Facebook or Twitter. And if you appreciate our newsletter, please let people know that they can subscribe for no cost at this link. Thank you for supporting our work.

Rate this article
4.1- 91 ratings
About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
Tired of the ads on our website?

Now you can browse our website completely ad-free for just $5 / month. Stay up to date on breaking health news and support our work without the distraction of advertisements.

Browse our website ad-free
Join over 150,000 Subscribers at The People's Pharmacy

We're empowering you to make wise decisions about your own health, by providing you with essential health information about both medical and alternative treatment options.