Do You Still Believe in the “Chemical Imbalance Theory of Mental Illness”?

Image Source: Gutenberg Encyclopedia – CC BY-SA 3.0

It continues to come as a great surprise for many people to learn that psychiatry’s leading authorities, including the former longtime director of the National Institute of Mental Health (NIMH), have discarded the “chemical imbalance theory of mental illness”—an idea which has had a profound impact on millions of emotionally suffering people and on our entire society.

Acceptance of the idea that a chemical imbalance causes depression transformed the public’s comfort level about taking antidepressants. With a belief that a chemical imbalance caused their depression, accompanied by repeatedly hearing that Prozac, Zoloft, and other selective serotonin reuptake inhibitor (SSRI) antidepressants “work to correct this imbalance,” it seemed irresponsible not to take these antidepressants.

So between 1988 (when the first of the SSRIs, Prozac, hit the market) and 2008, the rate of antidepressant use in the United States increased nearly 400 percent. By 2013, 16.7 percent of American adults reported filling one or more prescriptions for psychiatric drugs; and a 2022 Center for Disease Control and Prevention (CDC) survey (March 30-April 11) reported 23.5 percent of American adults (29.6 percent women) “took prescription medication for mental health.” Among children, Psychology Today reported in 2021: “In the USA, 1 in 12 children are on psychiatric drugs, including 1.2 percent of pre-schoolers and 12.9 percent of 12- to 17-year-olds.”

If you knew that psychiatric drugs—similar to other psychotropic substances such as marijuana and alcohol—merely “take the edge off” rather than correct a chemical imbalances, would you be more hesitant about using them, and more reluctant to give them to your children? Drug companies certainly believe you would be less inclined if you knew the truth, and that is why we were early on flooded with commercials about how antidepressants “work to correct this imbalance.”

So, when exactly did psychiatry discard its chemical imbalance theory? While researchers began jettisoning it by the 1990s, one of psychiatry’s first loud rejections was in 2011, when psychiatrist Ronald Pies, Editor-in-Chief Emeritus of the Psychiatric Times, stated: “In truth, the ‘chemical imbalance’ notion was always a kind of urban legend—never a theory seriously propounded by well-informed psychiatrists.” Pies is not the highest-ranking psychiatrist to acknowledge the invalidity of the chemical imbalance theory.

Thomas Insel was the NIMH director from 2002 to 2015, and in his recently published book, Healing (2022), he notes, “The idea of mental illness as a ‘chemical imbalance’ has now given way to mental illnesses as ‘connectional’ or brain circuit disorders.” While this latest “brain circuit disorder” theory remains controversial, it is now consensus at the highest levels of psychiatry that the chemical imbalance theory is invalid.

The jettisoning of the chemical imbalance theory should have been uncontroversial twenty-five years ago, when it became clear to research scientists that it was a disproved hypothesis. In Blaming the Brain (1998), Elliot Valenstein, professor emeritus of psychology and neuroscience at the University of Michigan, detailed research showing that it is just as likely for people with normal serotonin levels to feel depressed as it is for people with abnormal serotonin levels, and that it is just as likely for people with abnormally high serotonin levels to feel depressed as it is for people with abnormally low serotonin levels. Valenstein concluded, “Furthermore, there is no convincing evidence that depressed people have a serotonin or norepinephrine deficiency.” But how many Americans heard about this?

In a 2007 survey, 84.7 percent of 262 undergraduates believed it “likely” that chemical imbalances cause depression. While I cannot locate a more recent survey, my experience with patients, the media, and even many doctors is that the majority of them continue to believe in the chemical imbalance theory of depression.

Somewhat analogously, a 2015 survey reported that 42 percent of all Americans—and 51 percent of Republicans—continue to believe that WMDs were found in Iraq. Once attached to a belief, it is difficult for many people to let go of it. Carl Sagan, a fierce advocate of skeptical inquiry, observed, “One of the saddest lessons of history is this: If we’ve been bamboozled long enough, we tend to reject any evidence of the bamboozle. We’re no longer interested in finding out the truth. The bamboozle has captured us. It’s simply too painful to acknowledge, even to ourselves, that we’ve been taken.”

Ronald Pies claimed in the Psychiatric Times in 2014 that the American Psychiatric Association (APA), the guild of American psychiatrists, fulfilled its obligation to inform the general public with a 2000 public statement that begins: “The exact causes of mental disorders are unknown, but an explosive growth of research has brought us closer to the answers.” Pies did acknowledge that psychiatry should have been clearer and louder, “Shouldn’t psychiatrists in positions of influence have made greater efforts to knock down the chemical imbalance hypothesis, and to present a more sophisticated understanding of mental illness to the general public? Probably so.”

Don’t feel like you were not paying attention if you did not know that psychiatry has long discarded the chemical imbalance theory of mental illness. It was news to National Public Radio correspondent Alix Spiegel, and she is the granddaughter of psychiatrist John Spiegel, a former president of the APA.

In her 2012 NPR story, Spiegel recounts how as a depressed teenager, she and her parents were told the following by a Johns Hopkins Hospital psychiatrist about her depression: “It’s biological, just like diabetes, but it’s in your brain. This chemical in your brain called serotonin is too, too low. There’s not enough of it, and that’s what’s causing the chemical imbalance. We need to give you medication to correct that.” Then, Spiegel tells us, the psychiatrist handed her mother a prescription for Prozac.

As a journalist, Spiegel did some digging. She talked to Joseph Coyle, Harvard Medical School professor of neuroscience and editor of one of psychiatry’s most prestigious journals, who told her: “Chemical imbalance is sort of last-century thinking. . . . It’s really an outmoded way of thinking.”

Spiegel tried to discover why psychiatry has not made greater efforts at publicizing its jettisoning of the chemical imbalance hypothesis. Alan Frazer, chair of the department of pharmacology at the University of Texas Health Science Center in San Antonio, told her that framing depression as a chemical imbalance has allowed patients to feel better about taking a drug and to “feel better about themselves, if there was this biological reason for them being depressed, some deficiency, and the drug was correcting it.”

Apparently, authorities at the highest levels have long known that the chemical imbalance theory was a disproven hypothesis, but they have viewed it as a useful “noble lie” to encourage medication use.

If you took SSRI antidepressants believing that these drugs helped correct a chemical imbalance, how does it feel to learn that this theory has long been disproven? Will this affect your trust of current and future claims by psychiatry? Were you prescribed an antidepressant not from a psychiatrist but from your primary care physician, and will this make you anxious about trusting all healthcare authorities?

Trust is important in all of healthcare, but it is absolutely vital in helping someone with depression. In my three decades plus as a practicing clinical psychologist, my experience is that depression is a reaction to loss and other pains, and a loss of trust is one of those pains. Thus, discovering that one has misplaced trust in a doctor can make one’s depression worse.

Primum non nocere—first do no harm—should be common sense for any healthcare professional, but perhaps a regular reminder is necessary.

Bruce E. Levine, a practicing clinical psychologist, writes and speaks about how society, culture, politics, and psychology intersect. His most recent book is A Profession Without Reason: The Crisis of Contemporary Psychiatry—Untangled and Solved by Spinoza, Freethinking, and Radical Enlightenment (2022). His Web site is