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Tuesday, February 15, 2011

There's no such thing as a "chemical imbalance"

I've known at least a hundred clients who think that the cause of their symptoms might be a "chemical imbalance." Some have said, "maybe I don't have enough Serotonin." It bothers me, every time, because there is no such thing.

About 30 to 40 years ago, some scientists hypothesized that anti-depressants corrected a chemical imbalance in the brain, primarily Serotonin. 
But as early as 1994, it became clear that the hypothesis of a chemical imbalance in the brain was over-simplistic, and, there was not a significant amount of research to support the hypothesis. 

Dozens of ideas about the brain have come and gone.
Even though it's false, the chemical imbalance ideas
sticks around because of pharmaceutical marketing.

For years, scientists had studied Serotonin in the human brain and there was no indication that increasing Serotonin or decreasing Serotonin would cure or cause depression. Interestingly, one anti-depressant used in Europe decreases Serotonin availability in the brain.

Some ideas die hard. Pharmaceutical Corporations still make the claim that antidepressants "may correct a chemical imbalance in the brain." Pharmaceutical sales reps continue to tell physicians the same thing, and doctors tell their patients.

Why do Pharmaceutical commercials and sales reps still mention the chemical imbalance hypothesis if its not true? There's no law against it. I suspect they continue to use it because it sounds so simple: chemical imbalance + pill = cure. As simple as adding salt to french fries.

The "Alternative Medicine" industry has also climbed on the bandwagon with all sorts of pills that allegedly cure this chemical imbalance - 5HT, SAMe, and St. John's Wort. None of these supplements seem to work very well in clinical trials, and they also can complicate existing treatments, for example, by lessening the effects of other medications. These supplements can have undesirable side effects like antidepressants (weight gain, insomnia, irritability, nausea, etc...) - so much for au natural.

Even if there was a chemical imbalance in your brain, it doesn't mean that it was the cause of your depression. It is extremely difficult to understand cause and effect. Life events that we find depressing may increase the presence of one neuro-modulator while decreasing another. Would it be fair to say that the change in neuromodulators caused your depression? or, did the upsetting life stress cause your brain to change it's chemistry in order to make you feel a certain way and for a certain reason? Is it possible that we need to have certain feelings? Is it possible that certain feeling states can become habitual or maintained? Is this in our control?

There are two primary neurotransmitters: GABA and Glutamate. Other chemicals, like Serotonin, Dopamine, Epinephrine and Nor-epinephrine are called neuromodultors and they modulate GABA and Glutamate. There are many neuromodulators: Opiates (Endorphins and Enkephalins), peptides and hormones (estrogen, testosterone, etc...) which also modulate GABA and Glutamate. At this point, information about neurochemistry becomes much more complex, and this may be why doctors appeal to the "chemical imbalance" hypothesis - it's less time consuming and so simple to understand. Pass the salt.

The "chemical imbalance" phrase has been around a long time. We tend to believe things the more that we hear it. That's why commercials are played repeatedly, ad nauseum. Pretty soon, you're doing the work of the sales rep: you go to the doctor and ask them for the medication that the pharmaceutical company has been telling you that you need! "Hey doc, I've been feelin' down way too long, maybe I have one of them chemical imbalances; maybe I need that medication in the commercial with the smiling bubble?"

The reality is that nobody knows if antidepressants really work and, when scientists think that they do work, they are unable to explain why - with any degree of certainty. It sounds terrible, but it's terribly true. One factor that has confused and confounded scientists for decades is the Placebo Affect. 

It can be hard to believe that the placebo effect can be powerful enough to cure depression, anxiety, and alleviate other health problems. There are many studies on the placebo effect. A couple years ago, one study found that people given Ibuprofen, for pain management, did just as well as people given Oxycontin - if they believed that they were taking Oxycontin. About 33% of Americans are susceptible to the placebo affect. Perhaps this is why not everyone is helped by antidepressants. Some people feel "cured" while others feel nothing; some people feel "numb" while others feel "a little better."

Antidepressants are pills with side effects. Sometimes people feel better when they take them, sometimes nothing changes, and sometimes they feel worse; in rare cases, they are associated with suicide ideation, suicide behavior, and self mutilation behaviors. 

There are alternatives to medication, such as Cognitive Behavioral Therapy (CBT) and other types of therapy. Medication is often given as the first line of treatment by physicians, however, it is probably best used as a last line of treatment.

A significant advantage of therapy is that you learn to overcome your problems or symptoms independently of medication. Also, there tend to be no negative side effects to therapy, such as weight gain, loss of sex drive, or others.

Addendum (2012):
Since writing this post, I was finally able to read The Emperor's New Drugs by Dr. Irving Kirsch. No one has conducted a more thorough scientific investigation into the effectiveness of Anti-Depressants as he. It turns out that, with regards to depression and anxiety, Anti-Depressants are no better than placebos. One of the most striking findings was that the effectiveness of Anti-Depressants was almost perfectly correlated with the amount of reported side effects. I strongly recommend this book to anyone who is prescribed Anti-Depressants.

Addendum (2014):
Medscape published this article below about psychiatry's official view of the cause of "mental illness." I re-posted the article here for educational purposes. In short, the article notes that, since 2005, the American Psychiatric Association has said that the cause is unknown; however, in my experience, I have yet to meet a psychiatrist who says this; every psychiatrist that I have done rounds with or talked with over the phone about a patient, or by patient reports, has said that the illness is caused by a chemical imbalance.

Nuances, Narratives, and the 'Chemical Imbalance' Debate in Psychiatry

Ronald W. Pies, MD
April 15, 2014

A Chemical Cliché: Introduction

Religions, cultures, and political groups all have their narratives -- usually favorable or flattering accounts of their origins and beliefs. But narratives are not the same as truths, and usually lack the nuances of truth, which is rarely black or white. To see how this applies to psychiatry, try answering the following question:
Which one of the following statements best characterizes the American Psychiatric Association (APA) 2005 position on the causes of mental illness?
1. All mental illness is caused by specific and identifiable chemical imbalances in the brain.
2. The most serious mental illnesses, such as schizophrenia and major depression, are caused by specific chemical imbalances.
3. Chemical imbalances of some sort cause some mental illnesses.
4. The exact causes of mental disorders are unknown.
Now, if you were to give credence to a recent online polemic posing as investigative journalism,[1] you would probably choose the first or second statement. In the narrative of the antipsychiatry movement, a monolithic entity called "Psychiatry" has deliberately misled the public as to the causes of mental illness, by failing to debunk the chemical imbalance hypothesis. Indeed, this narrative insists that, by promoting this little white lie, psychiatry betrayed the public trust and made it seem as if psychiatrists had magic bullets for psychiatric disorders. (Lurking in the back-story, of course, is Big Pharma, said to be in cahoots with Psychiatry so as to sell more drugs).
However, if you had actually investigated the APA's 2005 statement, you would have chosen statement #4. Here is the complete passage from the APA's Healthy Minds Website, intended for the general public[2]:
The exact causes of mental disorders are unknown, but an explosive growth of research has brought us closer to the answers. We can say that certain inherited dispositions interact with triggering environmental factors. Poverty and stress are well-known to be bad for your health -- this is true for mental health and physical health. In fact, the distinction between "mental" illness and "physical" illness can be misleading. Like physical illnesses, mental disorders can have a biological nature. Many physical illnesses can also have a strong emotional component.

Debunking an Urban Legend

In fact, in the same year as the APA statement, Drs. Thomas Insel and Remi Quirion wrote a seminal article[3] proposing that "...mental disorders need to be addressed as disorders of distributed brain systems with symptoms forged by developmental and social experiences...." They went on to consider how "...environmental factors during critical intervals of development exert long-term effects on gene expression..." and suggested that "...studying unconscious processes, motivation, or defenses, while at one time the sole province of psychoanalytic therapies, are now also in the domain of cognitive neuroscience."
Does this sound like a simplistic chemical imbalance hypothesis? I don't think so. But then, why do antipsychiatry groups and bloggers fail to note the nuances of what psychiatrists have been saying for at least the past decade? My guess is that doing so would undermine the derogatory narrative they wish to promote. And, of course, nuanced statements do not gin up public opinion or sell books.
OK -- but weren't there many psychiatrists, in the 1980s and 1990s, who did advocate a purely biochemical theory of mental illness, often using the metaphor of the chemical imbalance to explain mental disorders to their patients? It's difficult to answer this question, except in an anecdotal way, but it's probably true that some psychiatrists did hold a purely biocentric view; and, alas, some undoubtedly used the expression "chemical imbalance" in their clinical practice, without putting it into a broader context for their patients.
It's also true, as critics of the chemical imbalance hypothesis point out, that the term "imbalance" is misleading. In order to validate an imbalance, we must first have a quantitative understanding of the optimal neurochemical balance in the brain -- and, given the scores of neurotransmitters now identified, this balance has yet to be ascertained. That said, I am not aware of any concerted effort by academic psychiatrists, psychiatric textbooks, or official psychiatric organizations to promote a simplistic chemical imbalance hypothesis of mental illness. That is what I meant when, in a 2011Psychiatric Times piece, I referred to the chemical imbalance hypothesis as an "urban legend."[4]
But still, 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. There were sincere attempts to do just that, by several prominent psychiatrists -- beginning nearly 50 years ago, with the developers of the catecholamine hypothesis. As psychiatrist Joseph Schildkraut and neuroscientist Seymour Kety wrote in 1967[5]:
Whereas specific genetic factors may be of importance in the etiology of some, and possibly all, depressions, it is equally conceivable that early experiences of the infant or child may cause enduring biochemical changes, and that these may predispose some individuals to depressions in adulthood. It is not likely that changes in the metabolism of the biogenic amines alone will account for the complex phenomena of normal or pathological affect.
Note the nuanced view of causality in this formulation -- allowing for the possibility that chemical changes in the brain are effects of early experience, but also predisposing factors in some subsequent depressive episodes. Note that Schildkraut and Kety did not argue that "chemical imbalances" per se cause depression.
To the extent the "chemical imbalance" notion took hold in our popular culture, it was due mainly to distorted or oversimplified versions of the catecholamine hypothesis. These were often depicted in drug company ads; pop psychology magazines; and, in recent years, on misinformed Websites and blogs. In short, the "chemical imbalance theory" was never a real theory, nor was it widely propounded by responsible practitioners in the field of psychiatry.

A Biopsychosocial Balance

Psychiatry's critics also conveniently omit reference to what was arguably the most prevalent paradigm in academic psychiatry, during the 1980s and beyond: the biopsychosocial model (BPSM) of Dr. George Engel.[6] The BPSM has been subjected to much criticism, and some would argue that few psychiatrists nowadays use the BPSM in a systematic, evidence-based manner.[7,8] And in recent years, several prominent psychiatrists have warned that "...pharmacotherapy and psychotherapy, the major treatment modalities in psychiatry, have become fragmented from one another, creating an artificial separation of the psychosocial and biological domains in psychiatry."[9]
These are worrisome observations. But one thing is beyond dispute: The BPSM can hardly be reduced to a chemical imbalance theory of mental illness. As far back as 1991, in my book on psychotherapy for the general public, I wrote, "In recent years, the "biopsychosocial" model of mental illness has gained prominence. This holds that mental problems have biological, psychological, and social roots. Therapy may therefore involve treatment in all three spheres."[10]
I was far from the only psychiatrist promoting the biopsychosocial model -- and none of my academic colleagues, to my knowledge, publicly endorsed a simplistic chemical imbalance model as a blanket explanation for all mental illness. Indeed, over 20 years ago, the late Dr. Theodore Nadelson -- one of my teachers and a highly respected psychiatrist -- wrote the following in his foreword to my 1994 biopsychosocial textbook on psychiatric diagnosis and treatment[11]:
Neuronal tissue grows in response to its environment at least as much as it is obedient to any lockstep process choreographed immutably by the "gene machine." We are creatures in nature, but we create our own nature.... If we are to understand patients and, as doctors, to help them, we require the broadest base.... [In addition to biological research] we should also pursue greater understanding of the psychological and social environment. That task is further informed by literature -- poetry, philosophy, theater. That is our "biology" also.
Ted Nadelson understood that the brain is the crucible in which all the elements of human life intermingle, including our genetic makeup; our brain chemistry; and the influences of parents, culture, ethnicity, and even diet. Derangements, deficiencies or abnormalities in any of these biopsychosocial elements can lead to what we call, for lack of a better term, mental illness, which often represents the end result of innumerable interacting "pathogens."
Thus, in the introduction to my 1994 textbook, I wrote that "...the central assumption throughout the text is that the clinician must be able to integrate the complex biological, psychological and sociocultural data of the case at hand."[11] Most well-trained psychiatrists, in my experience, have always understood this need and done their best to fulfill it in practice.
The Nobel Prize-winning psychiatrist and neuroscientist Dr. Eric Kandel observed that "...all mental processes, even the most complex psychological processes, derive from operations of the a corollary, behavioral disorders that characterize psychiatric illness are disturbances of brain function, even in those cases where the causes of the disturbances are clearly environmental in origin."[12] But in practice, Kandel is no biological reductionist. He is certainly no fan of a chemical imbalance hypothesis! Rather, Kandel paints a picture of the new psychiatry, in which psychoanalytic and biological constructs complement and reinforce one another.
It is time for psychiatry's critics to drop the conspiratorial narrative of the "chemical imbalance" and acknowledge psychiatry's efforts at integrating biological and psychosocial insights.
Editor’s Note: A slightly shorter, modified version of this piece originally appeared on the Psychiatric Times Website.


  1. Levine BE. Psychiatry now admits it's been wrong in big ways -- but can it change? Truthout. March 5, 2014. Accessed April 9, 2014.
  2. American Psychiatric Association. What is mental illness? Let's Talk Facts brochure. 2005. Accessed April 9, 2014.
  3. Insel TR, Quirion R. Psychiatry as a clinical neuroscience discipline. JAMA. 2005; 294:2221-2224. Abstract
  4. Pies R. Psychiatry's new brain-mind and the legend of the "chemical imbalance." Psychiatric Times. July 11, 2011. Accessed April 9, 2014.
  5. Schildkraut JJ, Kety SS. Biogenic amines and emotion. Science. 1967;156:21-37. Abstract
  6. Engel GL. The need for a new medical model: a challenge for biomedicine. Science. 1977;196:129-136. Abstract
  7. Kontos N. Perspective: biomedicine -- menace or straw man? Reexamining the biopsychosocial argument. Acad Med. 2011;86:509-515.Abstract
  8. Ghaemi SN. The rise and fall of the biopsychosocial model. Br J Psychiatry. 2009;195:3-4. Abstract
  9. Gabbard GO, Kay J. The fate of integrated treatment: whatever happened to the biopsychosocial psychiatrist? Am J Psychiatry. 2001;158:1956-1963.
  10. Pies R. Psychotherapy Today: A Consumer's Guide to Choosing the Right Therapist. St. Louis: Manning Skidmore Roth; 1991.
  11. Pies R. Clinical Manual of Psychiatric Diagnosis and Treatment: A Biopsychosocial Approach. Washington, DC: American Psychiatric Press; 1994.
  12. Kandel ER. Psychiatry, Psychoanalysis and the New Biology of Mind. Washington, DC: American Psychiatric Publishing; 2005.

Mental Health Advice Disclaimer

The information included in this post and blog are for educational purposes only. It is not intended nor implied to be a substitute for professional mental health treatment or medical advice. The reader should always consult his or her mental health provider to determine the appropriateness of the information for their own situation or if they have any questions regarding a mental health or medical condition or treatment plan. Reading the information on this website does not create a therapist-patient relationship.

1 comment:

  1. Absolutely amazingly put. I couldn't agree more with you. The placebo effect does wonders. If the mind believes something to be true than it can and will be. I once had a friend in high school tell me that if I thought I was skinny, I would be skinny. Oddly enough, I began working on my outward thinking and feeling about myself, in turn, I lost weight. Which, what had really happened was when I felt better about myself, I was more active, I ate less (I eat when depressed or laying around watching tv) and I lost weight. I didnt lose a huge amount but I could tell a difference in myself. Of course that did not last and I began to believe it was not working anymore and didnt. We can train our minds to think what we would like to. I love that. I do however, believe in medications used as a stepping stone for those "too far gone" as they would put it. Or in other words, unable to cope right away. Maybe that perfect "sugar" pill *wink wink* would be nice to help them start somewhere and as they began to grow stronger, down the dosage *wink*, and off they go. Training them that they are strong enough to do it on their own. Little trickery if you may have it. Excellent post!!!