The “chemical imbalance” myth

June 30, 2008 in Depression, Myths & Truths | 60 comments

serotonin illustration “A theory that is wrong is considered preferable to admitting our ignorance.” – Elliot Vallenstein, Ph.D.

The idea that depression and other mental health conditions are caused by an imbalance of chemicals in the brain is so deeply ingrained in our psyche that it seems almost sacrilegious to question it.

Direct-to-consumer-advertising (DCTA) campaigns, which have expanded the size of the antidepressant market (Donohue et al., 2004), revolve around the claim that SSRIs (the most popular class of antidepressants) alleviate depression by correcting a deficiency of serotonin in the brain.

For example, Pfizer’s television advertisement for Zoloft states that “depression is a serious medical condition that may be due to a chemical imbalance”, and that “Zoloft works to correct this imbalance.”

Other SSRI advertising campaigns make similar claims. The Effexor website even has a slick video explaining that “research suggests an important link between depression and an imbalance in some of the brain’s chemical messengers. Two neurotransmitters believed to be involved in depression are serotonin and norepinephrine.” The video goes on to explain that Effexor works by increasing serotonin levels in the synapse, which is “believed to relieve symptoms of depression over time.”

These days serotonin is widely promoted as the way to achieve just about every personality trait that is desirable, including self-confidence, creativity, emotional resilience, success, achievement, sociability and high energy. And the converse is also true. Low serotonin levels have been implicated in almost every undesirable mental state and behavioral pattern, such as depression, aggressiveness, suicide, stress, lack of self-confidence, failure, low impulse control, binge eating and other forms of substance abuse.

In fact, the idea that low levels of serotonin cause depression has become so widespread that it’s not uncommon to hear people speak of the need to “boost their serotonin levels” through exercise, herbal supplements or even sexual activity. The “chemical imbalance” theory is so well established that it is now part of the popular lexicon.

It is, after all, a neat theory. It takes a complex and heterogeneous condition (depression) and boils it down to a simple imbalance of two to three neurotransmitters (out of more than 100 that have been identified), which, as it happens, can be “corrected” by long-term drug treatment. This clear and easy-to-follow theory is the driving force behind the $12 billion worth of antidepressant drugs sold each year.

However, there is one (rather large) problem with this theory: there is absolutely no evidence to support it. Recent reviews of the research have demonstrated no link between depression, or any other mental disorder, and an imbalance of chemicals in the brain (Lacasse & Leo, 2005; (Valenstein, 1998).

The ineffectiveness of antidepressant drugs when compared to placebo cast even more doubt on the “chemical imbalance” theory. (See my recent articles Placebos as effective as antidepressants and A closer look at the evidence for more on this.)

Folks, at this point you might want to grab a cup of tea. It’s going to take a while to explain the history of this theory, why it is flawed, and how continues to persist in light of the complete lack of evidence to support it. I will try to be as concise as possible, but there’s a lot of material to cover and a lot of propaganda I need to disabuse you of.

Ready? Let’s start with a bit of history.

The history of the “chemical imbalance” theory

The first antidepressant, iproniazid, was discovered by accident in 1952 after it was observed that some tubercular patients became euphoric when treated with this drug. A bacteriologist named Albert Zeller found that iproniazid was effective in inhibiting the enzyme monoamine oxydase. As its name implies, monoamine oxydase plays an essential role in inactivating monoamines such as epinephrine and norepinephrine. Thus, iproniazid raised levels of epinephrine and norepinephrine which in turn led to stimulation of the sympathetic nervous system – an effect thought to be responsible for the antidepressant action of the drug.

At around the same time, an extract from the plant Rauwolfia serpentina was introduced into western psychiatry. This extract had been used medicinally in India for more than a thousand years and was thought to have a calming effect useful to quite babies, treat insomnia, high blood pressure, insanity and much more. In 1953 chemists at Ciba, a pharmaceutical company, isolated the active compound from this herb and called it reserpine.

In 1955 researchers at the National Institutes of Health reported that reserpine reduces the levels of serotonin in the brains of animals. It was later established that all three of the major biogenic amines in the brain, norepinephrine, serotonin, and dopamine, were all decreased by reserpine (again, in animals).

In animal studies conducted at around the same time, it was found that animals administered reserpine showed a short period of increased excitement and motor activity, followed by a prolonged period of inactivity. The animals often had a hunched posture and an immobility that was thought to resemble catatonia (Valenstein, 1998). Since reserpine lowered levels of serotonin, norepinephrine and dopamine, and caused the effects observed in animals, it was concluded that depression was a result of low levels of biogenic amines. Hence, the “chemical imbalance” theory is born.

However, it was later found that reserpine only rarely produces a true clinical depression. Despite high doses and many months of treatment with reserpine, only 6 percent of the patients developed symptoms even suggestive of depression. In addition, an examination of these 6 percent of patients revealed that all of them had a previous history of depression. (Mendels & Frazer, 1974) There were even reports from a few studies that reserpine could have an antidepressant effect (in spite of reducing levels of serotonin, norepinephrine and dopanmine).

As it turns out, that is only the tip of the iceberg when it comes to revealing the inadequacies of the “chemical imbalance” theory.

The fatal flaws of “chemical imbalance” theory

As Elliot Valenstein Ph.D., Professor Emeritus of psychology and neuroscience at Michigan University, points out in his seminal book Blaming the Brain, “Contrary to what is often claimed, no biochemical, anatomical or functional signs have been found that reliably distinguish the brains of mental patients.” (p. 125)

In his book, Valenstein clearly and systematically dismantles the chemical imbalance theory:

Reducing levels of norepinephrine, serotonin and dopamine does not actually produce depression in humans, even though it appeared to do so in animals.
The theory cannot explain why there are drugs that alleviate depression despite the fact that they have little or no effect on either serotonin or norepinephrine.
Drugs that raise serotonin and norepinephrine levels, such as amphetamine and cocaine, do not alleviate depression.
No one has explained why it takes a relatively long time before antidepressant drugs produce any elevation of mood. Antidepressants produce their maximum elevation of serotonin and norepinephrine in only a day or two, but it often takes several weeks before any improvement in mood occurs.
Although some depressed patients have low levels of serotonin and norepinephrine, the majority do not. Estimates vary, but a reasonable average from several studies indicates that only about 25 percent of depressed patients actually have low levels of these metabolites.
Some depressed patients actually have abnormally high levels of serotonin and norepinephrine, and some patients with no history of depression at all have low levels of these amines.
Although there have been claims that depression may be caused by excessive levels of monoamine oxydase (the enzyme that breaks down serotonin and norepinephrine), this is only true in some depressed patients and not in others.
Antidepressants produce a number of different effects other than increasing norepinephrine and serotonin activity that have not been accounted for when considering their activity on depression.

Another problem is that it is not now possible to measure serotonin and norepinephrine in the brains of patients. Estimates of brain neurotransmitters can only be inferred by measuring the biogenic amine breakdown products (metabolites) in the urine and cerebrospinal fluid. The assumption underlying this measurement is that the level of biogenic amine metabolites in the urine and cerebrospinal fluid reflects the amount of neurotransmitters in the brain. However, less than one-half of the serotonin and norepinephrine metabolites in the urine or cerebrospinal fluid come from the brain. The other half come from various organs in the body. Thus, there are serious problems with what is actually being measured.

Finally, there is not a single peer-reviewed article that can be accurately cited to support claims of serotonin deficiency in any mental disorder, while there are many articles that present counterevidence. Furthermore, the Diagnostic and Statistical Manual of Mental Disorders (DSM) does not list serotonin as the cause of any mental disorder. The American Psychiatric Press Textbook of Clinical Psychiatry addresses serotonin deficiency as an unconfirmed hypothesis, stating “Additional experience has not confirmed the monoamine depletion hypothesis” (Lacasse & Leo, 2005).

When all of this evidence is taken in full, it should be abundantly clear that depression is not caused by a chemical imbalance.

But, as Valenstein shrewdly observes, “there are few rewards waiting for the person who claims that “the emperor is really nude” or who claims that we really do not know what causes depression or why an antidepressant sometimes helps to relieve this condition.”

How have we been fooled?

There are several reasons the idea that mental disorders are caused by a chemical imbalance has become so widespread (and none of them have anything to do with the actual scientific evidence, as we have seen).

It is known that people suffering from mental disorders and especially their families prefer a diagnosis of “physical disease” because it does not convey the stigma and blame commonly associated with “psychological problems”. A “physical disease” may suggest a more optimistic prognosis, and mental patients are often more amenable to drug treatment when they are told they have a physical disease.

Patients are highly susceptible to Direct-to-Consumer-Advertising (DCTA). It has been reported that patients are now presenting to their doctors with a self-described “chemical imbalance” (Kramer, 2002). This is important because studies show that patients who are convinced they are suffering from a neurotransmitter defect are likely to request a prescription for antidepressants, and may be skeptical of physicians who suggest other interventions such as cognitive behavioral therapy (DeRubeis et al., 2005). It has also been shown that anxious and depressed patients “are probably more susceptible to the controlling influence of advertisements (Hollon MF, 2004).

The benefit of the chemical imbalance theory for insurance companies and the pharmaceutical industry is primarily economic. Medical insurers are primarily concerned with cost, and they want to discourage treatments (such as psychotherapy) that may involve many contact hours and considerable expense. Their control over payment schedules enables insurance companies to shift treatment toward drugs and away from psychotherapy.

The motivation of the pharmaceutical companies should be fairly obvious. As mentioned previously, the market for antidepressant drugs is now $12 billion. All publicly traded for-profit companies are required by law to increase the value of their investor’s stock. Perhaps it goes without saying, but it is a simple fact that pharmaceutical companies will do anything they legally (and sometimes illegally) can to maximize revenues.

Studies have shown that the advertisements placed by drug companies in professional journals or distributed directly to physicians are often exaggerated or misleading and do not accurately reflect scientific evidence (Lacasse & Leo, 2005). While physicians deny they are being influenced, it has been shown repeatedly that their prescription preferences are heavily affected by promotional material from drug companies (Moynihan, 2003). Research also suggests that doctors exposed to company reps are more likely to favor drugs over non-drug therapy, and more likely to prescribe expensive medications when equally effective but less costly ones are available (Lexchin, 1989). Some studies have even shown an association between the dose and response: in other words, the more contact between doctors and sales reps the more doctors latch on to the “commercial” messages as opposed to the “scientific” view of a product’s value (Wazana, 2000).

The motivation of psychiatrists to accept the chemical imbalance theory is somewhat more subtle. Starting around 1930, psychiatrists became increasingly aware of growing competition from nonmedical therapists such as psychologists, social workers and counselors. Because of this, psychiatrists have been attracted to physical treatments like drugs and electroshock therapy that differentiate them from nonmedical practitioners. Psychiatry may be the least respected medical specialty (U.S. General Accounting Office report). Many Americans rejected Fruedian talk therapy as quackery, and the whole field of psychiatry lacks the quality of research (randomized, placebo-controlled, double-blind experiments) that serves as the gold-standard in other branches of medicine.

Dr. Colin Ross, a psychiatrist, describes it this way:

“I also saw how badly biological psychiatrists want to be regarded as doctors and accepted by the rest of the medical profession. In their desire to be accepted as real clinical scientists, these psychiatrists were building far too dogmatic an edifice… pushing their certainty far beyond what the data could support.”

Of course there are also many “benefits” to going along with the conventional “chemical imbalance” theory, such as free dinners, symphony tickets, and trips to the Caribbean; consultancy fees, honoraria and stock options from the pharmaceutical companies; and a much larger, growing private practice as the $20 billion spent by drug companies on advertising brings patients to the office. Psychiatrists are just human, like the rest of us, and not many of them can resist all of these benefits.

In sum, the idea that depression is caused by a chemical imbalance is a myth. Pharmaceutical ads for antidepressants assert that depression is a physical diseases because that serves as a natural and easy segue to promoting drug treatment. There may well be biological factors which predispose some individuals toward depression, but predisposition is not a cause. The theory that mental disorders are physical diseases ignores the relevance of psychosocial factors and implies by omission that such factors are of little importance.

Stay tuned for future articles on the psychosocial factors of depression, the loss of sadness as a normal response to life, and the branding of new psychological conditions as a means of increasing drug sales.

Recommended resources

Blaming the Brain, by Elliot Valenstein Ph.D.
Rethinking Psychiatric Drugs, by Grace Jackson M.D.
America Fooled: The truth about antidepressants, antipsychotics and how we’ve been deceived, by Timothy Scott Ph.D.
The Loss of Sadness, by Alan Horwitz and Jerome Wakefield
The Myth of the Chemical Cure, by Joanna Moncrieff

Tags: antidepressants, chemical, health, imbalance, mental

60 comments

Comments feed for this article

Jacqueline Wallis on July 1, 2008 at 4:18 am

Well I’d agree that antidepressants aren’t the answer and with the psychology of the psychiatric profession.

However, andecdotal though my evidence might be, I suffered for over 40 years and now I have been calm, happy and energetic with no relapse for over two years since I changed my way of eating with Kathleen des Maisons book Potatoes not Prozac.

I know what I feel in my body after years of trying everything else and if it worked for me then there is hope for anybody.

Jacqueline
Kathleen DesMaisons, Ph.D. on July 1, 2008 at 8:08 am

I think you have presented a very valuable analysis. And yes, absolutely the market has been driven by the drug companies. However, I think you are throwing the baby out with the bathwater. I am the author of Potatoes Not Prozac a book that outlines alternatives to treating depression using a change in diet and behavior. It is not psychological, it is biochemical. And the results reported from hundreds of thousands have been profound. Depression lifts and goes away when people eat good food at regular intervals and take sugar out of their diets.

To say that depression is simply *psychosocial* is as incomplete as saying it can be treated only with drugs.

I think there is way more to the story, and I love a good dialogue.
admin on July 1, 2008 at 10:30 am

Jacqueline & Kathleen,

Thanks for your comments and participation.

I happen to agree with both of you that nutritional deficiencies are likely a contributing cause of depression. I also agree that dietary changes can relieve depression, and have seen that in my own experience (although I believe that increasing intake of saturated fat and cholesterol, rather than simple carbohydrates, is the best way to do it).

However, the fact that changes in diet can contribute to or relieve depression does not prove that depression has anything to do with a “chemical imbalance” in the brain. If dietary changes had their effect on depression primarily by acting on serotonin levels, then anything else that raised serotonin levels would relieve depression and anything that depleted serotonin levels would alleviate it. The evidence I’ve included in my article clearly suggests that is not true; therefore, the serotonin-depression theory is unsupportable.

There are several different pathways by which nutritional changes could act on depression that don’t involve serotonin or other brain chemicals as a primary mechanism. For example, deficiencies in both micronutrients (such as vitamin D) and macronutrients (fatty acids) have been shown to cause depression. The fact that dietary changes affect depression is not evidence that it is caused by low serotonin levels.

For the record, I didn’t say that depression is only psychosocial. In fact, I believe that depression is a multifactorial, heterogeneous condition with many different causes that are not necessarily the same in each person. To speak of a single cause or even single set of causes that is consistent for all people is overly reductionistic.

Yet this is exactly what the “chemical imbalance” theory does: it reduces a complex phenomenon (depression) to a simple imbalance of chemicals in the brain. It’s bad enough to blame depression on a single cause, but when that cause (serotonin deficiency) has been repeatedly disproved in the scientific literature, clinging to it as a viable theory is not only reductionistic – it is also misguided and inaccurate.

Chris
Kathleen DesMaisons, Ph.D. on July 1, 2008 at 10:55 am

Well, we can have fun agreeing to disagree

I think serotonin can be a part of it. And the studies you are citing doing a test in a very short term interval. It may be that serotonin depletion that persists for 6 weeks is a more accurate measure. For example, people who do Atkins generally crash into depression reaction about 6 weeks in…

But, honestly, I am not trying to convince you, only to nudge your healthy skeptic to stay open to the store.

The interesting thing for me is watching people get well. That is what I care about. Some might say doing the food is merely placebo. Could be.
But results are what counts.

I love that you are so thoughtful.

warmly,
kathleen
admin on July 1, 2008 at 11:25 am

Hi Kathleen,

Nice to hear back from you. Indeed, serotonin may be a part of it – but is it a correlation or a cause? It has been shown that certain life events and behavior can deplete serotonin levels, so the possibility has been raised by researchers that depression may cause serotonin deficiency and not the other way around.

Actually, in a previous article on the blog I have cited longitudinal studies which indicate that treatment with antidepressant drugs (which increase serotonin levels) is associated with poor outcomes over the long-term. In contrast to the six-week clinical trials you mention, these studies are looking at results over periods of months and even years.

Although food may have a placebo effect (nearly everything does), I do believe there are biochemical mechanisms influenced by nutrition that contribute to depression. I just happen to think serotonin isn’t primary in this equation.

I also agree that getting well is what matters most. However, *how* someone conceives of their illness and *how* someone gets well is also important. I like what Joanna Moncrieff, who is one of the foremost researchers in this field, has to say about this:

“The promotion of antidepressants has convinced millions of people to ‘recode their moods and their ills’ in terms of their brain chemistry (Rose 2004).

If people believe that it is brain chemicals that have made them depressed and that they only improved because a drug helped to rectify a chemical defect or imbalance, then they are likely to fear the recurrence of depression with every difficult period in their lives. In addition, they are not likely to recognize the things that they did to help themselves out of depression, because they attribute their recovery to a drug. If in contrast they had managed to get through the period without taking a drug that they thought sorted out their biochemistry, they would have had an experience of self-efficacy that could build their confidence and help them to face future problems with greater strength.”

This is analogous to the “give a man a fish, he eats for a day; teach a man to fish, he eats for life” parable. Teaching people that depression is caused by a chemical imbalance that requires drugs to correct is profoundly disempowering (not to mention completely false, according to the scientific literature). But it does wonders for drug sales!

Thanks again for your contribution, Kathleen.
Jacqueline Wallis on July 1, 2008 at 12:19 pm

Well I found all that utterly fascinating and thank you both very much.

As a psychologist as well as a ‘patient’ could I point out the ‘double whammy’ of the PnP programme has been in addressing both seratonin levels/brain chemistry AND behaviour. Built into the steps are numerous changes in behavioural patterns which are missing in purely pharmaceutical intervention and might throw light onto the delay factor in the effectiveness of artificial seratonin raisers.

I think the human organism, for mental health, needs to be proactive in changing negative attitudes/habits at the same time as the brain is healing and this is why the subtle mixture of behavioural and nutritive intervention works so well.

Jacqueline
admin on July 1, 2008 at 2:27 pm

Hi Jacqueline,

I agree that behavioral change is likely to be important in treating depression.

However, at the risk of beating a dead horse, I feel I need to again point out that there is no evidence that antidepressant drugs or dietary changes relieve depression (when they do) by increasing serotonin levels or modifying brain chemistry in any other way.

To be fair, it is possible that the drugs and diet work on other as yet unidentified neurotransmitters, or by some unknown mechanism involving brain chemistry. However, unless we discover that is the case – which is by no means inevitable – I believe it is irresponsible to continue promoting the idea that depression is caused by a “chemical imbalance”.
Kathleen DesMaisons, Ph.D. on July 1, 2008 at 3:14 pm

And we can simply agree to disagree on the definition of *evidence*.

And I am very happy to continue with the premise that of course depression is caused by a chemical imbalance, LOL.

Lotrich FE, Pollock BG.
Free in PMC Candidate genes for antidepressant response to selective serotonin reuptake inhibitors.
Neuropsychiatr Dis Treat. 2005 Mar;1(1):17-35.

Lotrich suggests that that the differences in outcomes or impact may be a function of gene types. You might want to read that one

And here is Prakash suggested that the analysis makes a difference…

Prakash A, Risser RC, Mallinckrodt CH.
The impact of analytic method on interpretation of outcomes in longitudinal clinical trials.
Int J Clin Pract. 2008 Jun 16. s

Therefore, whether or not underestimating (overestimating) within-group changes was conservative or anticonservative depended on the relative magnitude of the bias in each treatment and on whether within-group changes represented improvement or worsening.

Perhaps the difference is that I am open to hearing the other side and you are not, LOL….

I just think your argument would be more powerful if it were balanced.
I am learning a lot in the process.

kathleen
Kathleen DesMaisons, Ph.D. on July 1, 2008 at 3:19 pm

Hey Chris,

one other thought here…

I just got some context from your personal journey.
I have a feeling that our backgrounds are very similar.

I would be delighted to talk with you about treatment of some complex issues that medical science has written off as untreatable.

We could have that dialogue off line.

kathleen
Jacqueline Wallis on July 1, 2008 at 3:35 pm

Could we review ‘irresponsible’ for a moment.

If the patient accepts this diagnosis and then puts themselves utterly in the hands of the Pharmaceutical or Psychiatric industries then this would indeed be negating self responsibility.

However if acceptance of this diagnosis (and I utterly accept it after two years of personal experience) means feeling empowered to seek a natural, science based and proven program of healing then self responsibility is actually enhanced.

Sometimes empowering the sufferer and offering sound, practical and proven advice is the most powerful tool for healing we can give.

However I am still with you that this second option is not often offered by our current health service and I am glad to see you confronting the Pharmaceutical giants. Please though don’t bring a diagnosis which so many ‘know’ to be true as ammunition in your fight – rather address what they do with it.

Jacqueline
Rob on July 1, 2008 at 5:48 pm

It’s a hard call. I’m taking a supplement called Equalibrex (http://www.equalibrex.com) which is a 5-formula system of natural ingredients intended to increase well-being or alleviate depression or whatever. Many of its ingredients affect seratonin levels(5-htp and sam-e, for instance). I’ve noticed quite a noticeable difference in how I feel which is hard to pin on the placebo-effect. Now, i’m not discounting behavioral variables in equation, as I’m now a lot more active than before, but I do feel “picked up” so-to-speak.

Seratonin levels may very well be an indicator of depression, but I’m not going to assume some people are endemic to low levels and some are not. If one forcibly or artificially raises levels to make themselves feel better (through medication/supplement/exercise), of course seratonin would be the deciding variable – this does not mean those levels are “normal” or “raised” in other people for non-medicinal reasons.
admin on July 1, 2008 at 6:38 pm

Kathleen,

I am completely open to another point of view, so long as it makes sense to me and there is evidence to support it. By evidence, I am not exclusively referring to double-blind, placebo-controlled randomized trials. I do not think that is the only type of scientific inquiry we should engage in.

You should know that before I started researching depression, I believed what everyone else believes – that it was likely caused by some chemical imbalance in the brain. I clearly saw the role of nutrition, behavior, psychosocial, and other factors, but I thought that they were simply altering brain chemistry and therefore addressing the underlying chemical imbalance.

When I started the research I approached it with an open mind, and thus my mind was changed after a thorough review of the evidence.

I have looked at the studies you linked to, and when considered against the bulk of published research I do not believe they offer compelling evidence to support the serotonin hypothesis. As you well know, it is always possible to choose a study or even group of studies to support one’s view.

That’s why I have great respect for the work of researchers like Kirsch, Moncrieff, Valenstein, Hollon, Healy and others. They’ve spent the majority of their careers investigating this issue and reviewing all available and relevant studies, and their conclusions are all the same: when taken as a whole, the research does not support the theory that depression is caused by a chemical imbalance.

Is there a study out there that contradicts their conclusion? Sure there is. But there are so many more studies that support it. There are also fundamental flaws in the reasoning of the “chemical imbalance” hypothesis:

1. The psychiatric literature has rarely addressed how or why an excess or deficiency of serotonin or dopamine explains any particular mental disorder. There have been few attempts to explain how the proposed changes in neurochemistry actually affect the psychological phenomena called depression.

2. More than one hundred different neurotransmitters have been identified in the brain. Some of the NTs bind to as many as fifteen receptor types, each of which can presumably trigger a different cascading sequence of physiological changes. Add to this seemingly overwhelming complexity the fact that the receptors are continually changing in number, sensitivity and state and it becomes clear why their ensuing effects may differ from moment to moment.

3. In the case of serotonin, fifteen different receptors (5-HT1-15) have already been identified, and there may be more. Each of the fifteen receptor subtypes can be further subdivided (5-HT1 can be divided into 5-HT1-2, 5-HT1-3, etc.) There is virtually no information about what behavior or psychological states are likely to be affected by stimulating or blocking a particular receptor subtype.

4. There is no scientifically established ideal “chemical balance” of serotonin, let alone an identifiable pathological imbalance.

5. The claimed efficacy (which has been successfully disputed by Kirsch et al.) of SSRIs is often cited as support for the serotonin hypothesis. This is ex juvantibus reasoning – the fact that aspirin cures headache does not prove that headaches are due to low levels of aspirin in the brain.

6. EVEN IF it we could find a biochemical, anatomical or functional difference in the brains of mental patients (which no one has been able to consistently demonstrate), it would be wrong to assume that such differences are the *cause* of the disorder. The abnormalities could just as easily be the result, rather than the cause, of the disorder. Furthermore, it is well established that psychotherapeutic drugs used to treat mental disorders may induce long-lasting biochemical and even structural changes, which in the past were claimed to be the cause of the disorder, but again could just as easily be an effect of the treatment. It is now difficult to find mental patients who have not had a history of drug treatment, and because of this many of the brain abnormalities found in these patients are probably iatrogenic (produced by the treatment rather than being the cause).

7. Various experiences can also modify brain anatomy and function. Numerous experiments have shown that exposure to stressful situations can produce long-lasting brain changes. There is also evidence that stress can produce long-lasting changes in the same class of dopamine neurons that make them hypersensitive not only to drugs such as amphetamine, but also to subsequent exposure to stress.

The idea that serotonin isn’t the cause of depression may sound radical, but in fact it is not. As I pointed out in the article neither the DSM nor major psychiatry textbooks claim that depression is caused by serotonin. Furthermore, many well-known and influential psychiatrists (even those who prescribe antidepressants) and researchers have publicly stated their disagreement with this hypothesis:

“Given the ubiquity of a neurotransmitter such as serotonin and the multiplicity of its functions, it is almost as meaningless to implicate it in depression as it is to implicate blood.” – John Horgan, The Undiscovered Mind

“A serotonin deficiency for depression has not been found.” – Psychiatrist Joseph Glenmullen, clinical instructor of psychiatry at Harvard Medical School

“Indeed, no abnormality of serotonin has ever been demonstrated.” – Psychiatrist David Healy, former secretary of the British Association for Psychopharmacology

“We have hunted for big simple neurochemical explanations for psychiatric disorders and we have not found them.” – Psychiatrist Kenneth Kendler, co-editor-in-chief of Psychological Medicine

“Although it is often stated with great confidence that depressed people have a serotonin or norepinephrine deficiency, the evidence actually contradicts those claims.” – Professor Emeritus Elliot Valenstein, Michigan University

“I spent the first several years of my career doing full-time research on brain serotonin metabolism, but i never saw any convincing evidence that any psychiatric disorder, including depression, results from a deficiency of brain serotonin.” – Stanford psychiatrist David Burns, winner of the A.E. Bennett Award given by the Society for Biological Psychiatry for his research on serotonin metabolism

Kathleen, you suggested that I perhaps am not approaching this with an open mind. With respect, I ask you to consider whether that may not be true for you? I have presented what I think most people would agree is very compelling evidence against the serotonin hypothesis, and so far it would seem that you have been unaffected by this data. You have responded with two studies, neither of which indicate a role for serotonin in depression and neither of which contradict any of the claims I have made in my article.

I am honestly curious to know what *evidence*, however you are defining it, is the basis for your continued belief that depression is caused by serotonin deficiency? I really would like to see this evidence, because, contrary to what you implied in your last comment, I *am* approaching this with an open mind and have been from the begninning… way back when I also thought depression was caused by a lack of serotonin.

My review of the evidence changed my mind completely. Is there room for yours to change as well?

I’m not sure what part of my personal journey you’re referring to, but I would be happy to have a dialog offline with you. I do not believe there is any such thing as an “untreatable condition”, and I reject the validity of several Western medical diagnoses that use this language. There are too many examples that prove otherwise, and if even one person recovers, then the condition is no longer “untreatable” or “incurable”.
admin on July 1, 2008 at 6:47 pm

Jacqueline,

I can certainly see your perspective, i.e. that learning you had a “serotonin imbalance” led you to seek out natural remedies that could improve your condition.

I will steadfastly continue to point out that there is absolutely no way you can know whether you had a serotonin deficiency or not, nor does the evidence support a role for said deficiency in causing depression even if it exists.

I’m sorry to sound like a broken record here, but I’m sticking to my guns until someone presents evidence that changes my mind. While I greatly value personal experience and intuition in the healing process, one person (or even an entire country’s) belief that their depression is caused by serotonin deficiency doesn’t convince me that it’s so.

As Anatole France said, “Even if 50 million people say a foolish thing, it is still a foolish thing”. At one time nearly everyone thought the world was flat, and the earth was the center of the universe.

I certainly don’t mean to imply that what you are saying is foolish. Rather, I simply wish to point out that sometimes even our most sacred and unchallenged beliefs turn out to be false.

I completely agree with your statement that “empowering the sufferer and offering sound, practical and proven advice is the most powerful tool for healing we can give.”
admin on July 1, 2008 at 6:53 pm

Hi Rob,

Welcome to the Healthy Skeptic and thanks for your comment.

Again, sorry to be a stickler here but the fact that you improved on Equalibrex doesn’t prove that serotonin deficiency is at the root of your problem. As you mentioned, it could well be a placebo effect. Placebo is very powerful and can’t be discounted. Also, a product with several ingredients could have non-specific effects (i.e. effects not specifically related to serotonin) that could relieve the depression. It’s more than possible that the life changes you referred to could be responsible for the improvement. Finally, the shift could simply be due to regression to the mean.

And of course, it is *possible* that you improved because the supplement increased levels of serotonin in your brain. I am not saying it’s impossible. I’m just saying that the overwhelming majority of evidence doesn’t support that as the most likely explanation.
admin on July 1, 2008 at 7:19 pm

Kathleen,

I tried to email you but when I clicked on your name I am taken to a URL that must have a typo:

http://www,radiantreecovery.com

Even when I changed the comma to a period, it still didn’t work. You can send me an email through the “Contact” form on the blog.

Best,
Chris
Kathleen DesMaisons, Ph.D. on July 1, 2008 at 7:32 pm

Thanks, Chris.

I appreciate the dialogue.

warmly,
kathleen
admin on July 1, 2008 at 7:50 pm

Me too!

warmly as well,
chris
Jacqueline Wallis on July 2, 2008 at 3:57 am

Sticking to the simpler version you are happily admitting that no-one actually knows what causes it.

If we make an assumption (even if it is erroneous or incomplete) and in seeking a cure for this assumption we discover something which works then is this not a good thing.

We could argue about the science for an eternity, even if this mysterious little neurotransmitter were discovered and labelled, but the bottom line surely is that people are suffering. Some of those people, in pursuing healing, have discovered something which really works.

Would further investigation of this human proof of pudding not warrant further refining?

Thank you for making me even more sure of my diagnosis though and do continue to make us think.

Jacqueline
admin on July 2, 2008 at 10:21 am

Jacqueline,

I would not state the simple version as “no one knows what causes it”.

The simple version is: “the evidence is clear that depression is not caused by serotonin deficiency.”

That statement is not controversial according to the scientific literature. Furthermore, as I pointed out in my last post, it is extremely unlikely that depression is caused by a single “mysterious little neurotransmitter” – whether identified or unidentified.

I am glad that people like you have discovered something that works. That does not, however, prove anything about serotonin’s role in depression. The dietary and behavioral changes suggested in Kathleen’s program address depression through many different mechanisms of action. There is no proof that any of these mechanisms involve changing serotonin levels in the brain.

And of course, there is abundant proof that her program doesn’t work by raising serotonin levels. How do I know this? Because if that is how her program had its effect, then any intervention that raised serotonin would alleviate depression and any intervention that depleted serotonin would cause it. We have repeatedly seen that this is not the case.

May I respectfully ask why it so important for you to be sure of a diagnosis of “chemical imbalance”? In the face of so much evidence to the contrary, why and how do you continue to embrace this diagnosis? Does it somehow validate your experience in a way that wouldn’t happen if it were absent?

If we remove the “chemical imbalance” diagnosis from your equation, the fact remains that you were able to heal yourself using food and behavioral modifications from depression. Is that not enough? Why is the “chemical imbalance” theory necessary at all?

Jacqueline, is it possible that there is a belief system operating here that you are unwilling or unable to truly question? I ask because I still have not heard any compelling reason from you or Dr. DesMaisons why you continue to believe in “chemical imbalance” in light of the complete lack of evidence to support it.

There is no “argument” in the scientific literature. The literature is resoundingly clear that depression isn’t caused by serotonin deficiency, as I have presented in great detail here. The only argument is in the minds of people who have been conditioned to believe in the “chemical imbalance” theory by years of advertising, promotion and misinformed health care professional and media.

Best,
Chris
Jacqueline Wallis on July 2, 2008 at 1:03 pm

I am smiling at your hint that I am somehow unable or unwilling to question my diagnosis after 40+ years of untiring research on my own behalf.

I think there is some confusion between ‘chemical imbalance’ and ’seratonin deficiency’ in this. No it is not seratonin on its own – there are other chemicals and hormones out of ‘balance’ but we could argue terminology for days and probably get a huge Betaendorphin lift from the process LOL

I wish you well with your blog – I will continue to pursue my interest in Radiant Recovery and would invite anyone who is suffereing from depression, insomnia or addiction who is reading your blog to have a look at us on the website.

Jacqueline
admin on July 2, 2008 at 1:16 pm

Jacqueline,

I have defined “chemical imbalance” in this particular article as the idea that depression is caused by a deficiency of serotonin or norepinephrine in the brain.

I certainly don’t dispute that there is likely some biochemical involvement in depression. If that is what you mean by “chemical imbalance”, then we have had a very big miscommunication!

I am glad that Radiant Recovery has helped you to heal, and I was not suggesting that you don’t pursue it. If it works, it works! I was only curious (genuinely) to know what evidence you were basing your belief in “chemical imbalance” on.

Best wishes,
Chris
Jessiqua on July 13, 2008 at 4:45 pm

I knew there was a huge conspiracy behind it all. This is why I absolutely refused to believe anti-depressants and the like would ever help me, and eventually I learned how to be happy on my own and deal with my problems. Time is the best cure.

More people need to read this, and I’m so happy to have found it because now there is a way for me to explain to people why I believe it’s not the way to go.

Thank you for the wonderful article!
Chris on July 13, 2008 at 4:50 pm

Hi Jessiqua,

Welcome to The Healthy Skeptic and thanks for your participation.

I’m glad to know the article will be useful to you in the future. I also hope that many doctors, patients and parents will read this before deciding on antidepressants.

Warmly,
Chris
Rob on July 21, 2008 at 5:25 pm

Whoah – I forget I had written on here! Chris – very true.
Toby on August 18, 2008 at 2:18 pm

Thanks for the good work, Chris.

You are absolutely correct in stating that there is no such thing as a “chemical imbalance” in the brain. Sure, there may be vitamin or mineral deficiencies, and these can be found with simple blood tests or hair analyses.

What outrages me the most is that psychiatrists will tell you that you have a “chemical imbalance in the brain” to convinced you to take psychotropics, knowing full well that a) they haven’t given you a test to determine if you have one, and b) knowing full well that no such test exists, and c) that no imbalance even exists!

If any other doctor gave such a serious diagnosis involving a lifetime of care (i.e., drugs), without even so much as a simple blood test, they would most probably be brought up on malpractice charges and their license pulled.
Chris on August 18, 2008 at 2:33 pm

@Toby:

I couldn’t agree more, Toby. The so-called biological diagnosis of depression is analogous to the diagnosis of so-called diseases like “high cholesterol”, “seasonal affective disorder” and “pre-menstrual dysphoric disorder” which are indistinguishable from normal physiology. It’s all an attempt to push drugs to healthy people.

30 years ago the CEO of Merck upon retirement stated that his dream was always to “covert healthy people into customers”. Looks like his dream came true.

Only 10% of psychiatrists practice psychotherapy now. People are often prescribed drugs on their first visit and told they’ll have to take them for life.

This is criminal IMO.
Toby on August 20, 2008 at 1:11 pm

The answer to this insanity is websites like yours, Chris. Neither drug companies nor psychiatrists are going to give you the truth.
Jane on August 21, 2008 at 11:31 am

Thank you Chris for your excellent work with this article which I will propagate to my youtube viewership.

I can only speak for myself but I understand what depression is and how it is cured.

My depression manifested at age 7 with a crayola crayon drawing of me lying dead with a knife in my heart and blood everywhere.

My parents fighting with each other and their constant toxic psycho emotional histrionics made me depressed.Growing up thinking some Commie was going to nuke me in the 80s made me depressed.

Child abuse for years made me depressed. Bullying at school made me depressed. Religious guilt made me depressed. The crappy weather of New England made me depressed. The smoky, rundown, unlit home I grew up in made me depressed.

Being abandoned and turned over to the State made me depressed.

Later the psychiatric hospitals, the juvenile group homes, the psych meds all made me even more depressed.

Failing everything I tried to do as a young adult furthered my depression.

By the time I was 20 life to me was only depression of varying degrees of intensity. I wanted nothing more than to be free of my life.

By the time I was 32, I had been suicide attempt and depression free for a decade.

Following my last suicide attempt at age 20 I had a near death experience that changed my life and my approach to living.

I began each day by communing with the sun and ended each day by watching the sun set.

Later I substituted my coffee and cigarettes with yoga and tai chi as I continued my rituals.

In time I learned to meditate properly.

Year after year I healed everything in my life that had happened to me.

I forgave myself for not having any power of the events of my life. I forgave those that had trespassed against me and harmed me. The years of practicing tai chi and yoga 6 hours a day kept me feeling young and relaxed. The meditation allowed me to defuse all my triggers. I moved to a bright and sunny place with no winter and escaped SAD forever more.

I did everything in my power to micromanage and cope with everything that had ever made me depressed.

In my family my mother, sisters, brothers. They all continue to suffer from recurring depressions but not me

I alone escaped. I did the one thing no one in my family has ever done. I slowed down my life, took total responsibility for my past, present and future and I learned to unconditionally love myself and care for myself.

I have been depression free ever since.

I know what causes depression. I had physical,emotional,psychological and spiritual reasons for it. I fixed them all. As a result I know how to fix depression without therapy or drugs. In so doing, proved, at least to myself, that depression was no life long genetic chemical imbalance.

It pains me to read the comments left by teenagers on videos on youtube about depression, bipolar, etc, etc. These 13-19 year olds swear their problems are biological brain diseases or genetic chemical imbalances and they are growing up uncritically believing in and spreading the chemical imbalance pharmaganda to their peers. They encourage each other to use different psych meds. It works for ma and pa right?

Thanks for this article. You are doing good work Chris.
Froscha Wenig on August 22, 2008 at 5:35 pm

Hi Chris,

Thank you for writing this. My pill-popping family is convinced I should be on drugs for life. My mom makes great use of that analogy between diabetics taking insulin and depressed/bipolar patients taking psychiatric drugs. I disagree, at least as far as my own use, and now I can point to something substantial. Besides, insulin -helps- diabetics whereas the variety of drugs I’ve tried have only sent me down a spiral of dependency and side-effects that are more debilitating than the condition I supposedly have.

My psychiatrist recently agreed with me that I had been misdiagnosed as bipolar 5 yrs ago. The ridiculous thing is, I had one all-out manic episode AS A RESULT OF an antidepressant I later found out is a known trigger. (This information was not on my hospital discharge papers; a nurse happened to mention this to me privately after seeing traces of the drug in my blood.) I had also been on Paxil for two years before that for unipolar depression, though I had stopped a year before my episode — I now regard Paxil as the beginning of my descent into this medical nightmare. It made me too punchy at work too.

I have not had another manic episode since then and I did not go on drugs right away. I was doing fine, actually. However, I was scared into it by a lecture from a new GP who has a bipolar brother. She told me that it is normal for newly diagnosed bipolar patients to discount their diagnosis (ie. pathological denial), and that if I didn’t go on the drugs I would -inevitably- have another episode, only worse, and once I had a second I would be even -more- likely to have a third, and so on, with episodes becoming increasingly frequent. I was horrified at the idea of turning manic at work so I fell in line.

I am happy to learn this new word “iatrogenic” as I think my remaining problems (sleeping patterns increasingly erratic than before treatment, increased irritability, dark thoughts, not being able to hold down a job because of side-effects — NOT because of behavioural issues as one might expect from someone labelled bipolar) are caused by my so-called treatment on a variety of drugs these past 4 years. Okay, honestly, the Lamotrigine I’m currently on may help with depression/anxiety but it’s hard to separate true benefits from avoidance of the unique sickness and mood swings that happen with decreased dosages of anticonvulsants — in essence, the effects of detox rather than proof of the original pathology. Going back on full dosage as I’ve had to do recently (due to lack of support/stability in other areas of my life) seems akin to a heroin addict using again to avoid withdrawal rages.

I may still have a “mood disorder” (ha, don’t most people?!) but I’m starting to recognize the clearly observable link between my state of mind with external stressors, diet and sleep. I’m also on a waiting list for CBT therapy through an agency that offers free programs — but because it’s free it also takes a long time to get in. I was told I could expect to wait up to 10 months. As you say, the medical support system (even here in Canada, as idealized as it may be by Michael Moore, et al) is set up to profit by drug treatment, not support potentially more effective cognitive therapy, or dietitians, or alternative practitioners or the like.

Do you happen to have a full quote or reference to the Merck CEO’s dream? That reminds me of having read that Ron L. Hubbard once told someone he was planning to create a religion since his other get-rich-quick schemes hadn’t panned out — but, I cannot substantiate that quote. Wish I could.

Warm thanks,
Froscha
Chris on August 23, 2008 at 6:46 pm

Jane & Froscha,

Thanks very much to you both for sharing your experience with us.

The insulin analogy is ridiculous, of course. In the case of diabetes we can measure insulin deficiency quite easily, and the role of insulin in regulating glucose metabolism and producing diabetic symptoms is well understood.

In contrast, there is no test to establish a so-called “chemical imbalance” in depressed people, and nor do we know how psychotherapeutic drugs produce their effects.

The Merck CEO quote came from a book called “Selling Sickness”, by Alan Castells. I recommend it.
Charley on November 23, 2008 at 4:45 pm

Its not “too little serotonin” or “imbalance” -

Those of us who have suffered personality changing, life threatening depression aren’t often cured by a change in diet or reading a book any more than we are by going back to church.

You’ve reduced the entire psycho-pharmalogical subject to a comic strip.

It has more to do with what the brain DOES with these chemicals and how they work in the brain than it does with amounts.

The chemistry is far too complex to make this argument here.

The fact is that some of us, unable to function otherwise, have been able to reclaim our lives as a result.
Chris on November 23, 2008 at 11:14 pm

@Charley:

I’d be happy to read any evidence you send me which suggests that depression is reliably correlated with neurochemical function. The evidence overwhelmingly does not support such a correlation, as I’ve detailed here and on other posts.

I’d like to know what “complex chemistry” you’re referring to. I’ve reviewed literally hundreds of studies and quite a few books and textbooks on the neurochemistry of depression, and I have not found any consistent explanation for how dysregulated neurotransmitters cause depression. Again, I’ve written about this at length on my blog.

I have also suffered from life-threatening depression, so I do not wish to diminish in any way the intensity, seriousness and reality of such a condition.

However, the fact that whatever lifestyle changes you may have tried didn’t resolve your depression is not proof that it’s a disease caused by a neurochemical imbalance or dysfunction.

It sounds like you have had success with drugs. I’m very glad to hear you found something that works. But again, the fact that you improved with drugs doesn’t prove that depression is caused by a chemical imbalance. People with severe anxiety will usually experience relief when they drink alcohol. Does that prove their anxiety is caused by alcohol deficiency? Hardly. This kind of ex juvantibus reasoning is very common in the antidepressant/depression debate, but unfortunately it is fatally flawed.

If you wish to convince us that depression is caused by neurochemical dysregulation, you’ll have to do more than offer a vague reference to “chemistry” that is too “complex” to go into here.

I have no agenda. I was a fellow sufferer of severe depression, and began researching it years ago to learn more about it and find my way through it. This is the conclusion I’ve come to based on that considerable research and personal experience.
Toby on November 24, 2008 at 6:00 pm

Precisely, Chris.

No one is arguing that there is no such thing as severe depression or that people suffering from it are somehow inferior or “not strong enough.”

The argument is that there is no proof that problems like this are medical in nature caused by a “chemical imbalance in the brain.”

Psychoactive drugs may or may not cover up the symptoms, but they are not the cure, and worse, can come with considerable side effects, especially in the long term.

It would be nice to believe that modern medicine can solve all our problems for us. But years of fruitless research has proven that true solutions to emotional and psychological problems just can’t be found in a test tube.
Charley on November 27, 2008 at 1:48 pm

Chris -

Here is where I *think* we agree – psychiatry is *clearly* no science. Nobody can tell you exactly how these drugs work. There is no blood test for depression.

My concern with the arguments here are that you’ve reduced this argument to one like anemia and iron deficiency. You are tired, a blood test shows you are anemic, the doctor finds out why, you take iron supplements and fix it. Cured.

There is no such phenomenon as “too little serotonin” – it doesn’t work that way. This is simply a vastly oversimplified explanation for lay people who’s only understanding is “too little/too much/more is good”.

There are multiple types of receptors for serotonin. Serotonin is involved is much more than mood regulation. Different circuits in the brain utilize chemical mechanisms of communication in different ways. This is why I say “complex” – it is *incredibly* complex – I’m not an organic chemist, nor a neurologist or any other ‘ist’ qualified to give a lengthy dissertation on chemical systems of transmission and feedback in the brain. But come on – clearly you can see this much is true.

The fact that serotonin is involved in the regulation of mood is inferred from the changes seen when this chemical is manipulated in the brain. Much of our knowledge in science is made by inference.

We probably agree that this over-simplification has led to convincing a public that all their ills can be solved with medication. Clearly that is not the case. Insurance companies don’t want to pay for lengthy (an often unsuccessful) therapy. Pharmaceutical companies like to sell drugs. No secrets there.

Serotonin isn’t the only chemical involved – dopamine, nor epinephrine, epinephrine, GABA – all play huge roles. Add to the fact there are multiple types of receptors and that these chemicals and receptors are utilized in different ways and for different reasons in different people and yes, the chemistry is INCREDIBLY COMPLEX.

In a more self-centered vein I consider myself a “real” sufferer. This in contrast to someone in a period of soul-searching who seeks a remedy in a pill.

All of this is not to say I think ‘chemical imbalance’ is bunk. Is the change in chemistry a result of environment, bad behavior, bad habits, overbearing mothers or genetics. I don’t know.

What I *can* tell you is that medication has been the cornerstone of managing this ‘phenomenon’ for me. I hate taking medicine. Side effects? You better believe it. Medicine has even hurt me at one point by pushing me into a manic phase. Medicine alone does not work. I had to completely change my life. I had to stop drinking and using other drugs. I had to develop a different philosophy. I had to change jobs and surround myself with people that were congruent with my new direction. However, the meds remain a key. Without them I am erratic, suicidal and cannot function.

You make the comparison to alcohol. I’ve been there too. In fact, finding a way to address the underlying issues I was *medicating* with the alcohol allowed me to put it, and other drugs down an maintain strict sobriety for the past six years. It was a psychoactive drug called Depakote that allowed me to do that.

You just can’t over-simplify this. Between comments like ‘the true solutions to emotional and psychological problems just can’t be found in a test tube’ – and a drug company’s promotion of the idea that these issues can be solved with a pill is a reality: – and that is that these medications can be an invaluable *part* of successful treatment.

To say anything less is grossly insulting and does an incredible disservice to those in need.
Toby on November 27, 2008 at 5:48 pm

I agree with almost everything you say, Charley, except for the last two sentences — and I certainly don’t wish to insult you.

No one is denying that psychological problems are a part of this crazy game called life. We’ve all been there to one degree or another, some more than others.

The only real beef I have with psychiatrists and drug companies is that they purport that these drugs are “brain medicine,” which they clearly aren’t. We’re actually talking about very potent and often highly addictive chemicals that can wreak havoc throughout a human body (obesity, heart problems, neurological disturbances, etc.), especially if taken long term.

There are many other non-drug solutions ranging from alternative medicine to nutrition to severe allergy handlings to exercise to lifestyle changes. I know these types of solutions sound “airy fairy” to someone who is truly suffering emotionally. As I say, I’ve been there, I know. But the right one IS the way out, not drugs, which even psychiatrists admit only “manage” mental conditions.

But as I think we agree, we’re not looking at a proven pathology here. There is no lab test, no chemical imbalance to prove the existence of a visible “disease state.” (Not that what you or I may feel isn’t absolutely real)

I don’t mean to do a disservice to you or anyone else, but in my opinion, as someone who has been down that road, too, all people taking psychotropics should know what they’re getting themselves into, and if they’re still OK with it, then it’s their right to do with their bodies as they wish.

Best of luck.
Chris on November 27, 2008 at 7:49 pm

Charley,

I think we may just have to agree to disagree here. Like Toby, I found myself nodding my head in agreement as I read your post – right up until the end. I have never argued that depression does not have a biochemical element, nor that it doesn’t involve serotonin, norepinephrine or dopamine in any way. What I have consistently argued is that there is no reliable evidence that depression is caused by a deficiency or even imbalance of these brain chemicals, nor is there evidence that the drugs that are prescribed to “correct” these theoretical imbalances are more effective than other non-drug treatments.

Your argument that depression is a vastly complex disorder actually supports one of the main points I try to make over and over again here: powerful psychoactive drugs like SSRIs and SNRIs are dangerous precisely because depression is so complex. Our understanding of the brain and how it works is extremely limited; yet we feel no compunction about administering drugs with mechanisms we likewise do not fully understand and proven, serious side effects, including potentially irreversible anatomical and functional changes in the brain.

Most disturbingly, evidence has shown that antidepressant use causes changes in the brain that predispose patients to future depression, and that depressed people who take antidepressants are less likely to heal and more likely to relapse than those that don’t. Studies also indicate that antidepressant withdrawal is a much more serious problem than is commonly acknowledged, and that the symptoms of withdrawal are often mistakenly identified as a “relapse” into depression – which misleads both the doctor and patient into believing that the drug is necessary and the patient cannot function without it.

Charley, as someone who has suffered from severe depression I am very glad that you have found stability. This is important above all. However, I cannot agree that antidepressant drugs are a necessary part of the healing process for anyone based on the evidence I’ve reviewed and on my own experience. I am perfectly open to changing my mind if I encounter evidence which causes me to do so. Until then, I stand by what I’ve written here.
Charley on November 28, 2008 at 1:24 am

It certainly seems we agree on more than we disagree. I simply stop short of completely abandoning any idea of drug treatments and chemical explanations. I think there is evidence regardless of how twisted it may be used and presented by those with ulterior motives…

I completely support your indictment of the pharmaceutical industry – and those capitalizing on falsehoods to woo the public with magic pills.
Chris on November 28, 2008 at 11:45 am

I think there is evidence regardless of how twisted it may be used and presented by those with ulterior motives…

I think we do agree more than we disagree. I’d love to know what evidence you refer to here, because I review any legitimate data regardless of whether it supports my view.

I have not seen evidence that supports a neurochemical cause for depression. I have seen a lot of evidence suggesting a correlation between depression and neurochemical changes, but this is very different from suggesting that neurochemical factors cause depression.
Diogenes on December 14, 2008 at 12:20 am

I have seen a lot of evidence suggesting a correlation between depression and neurochemical changes, but this is very different from suggesting that neurochemical factors cause depression.

What do you mean by this exactly? Can you give any examples?
Chris on December 14, 2008 at 11:25 am
What do you mean by this exactly? Can you give any examples?

Sure. In scientific research it’s very important to understand and ascertain the difference between correlation and causation. Correlation indicates the strength of a linear relationship between two variables, whereas causation denotes a necessary relationship between one event and another event.

For example, it is well known that when we get a virus or infection the level of white blood cells in our blood rises to fight off the pathogen. So we could say there is a correlation between the number of white blood cells and the presence of a viral or bacterial infection. But as you know, it would be silly to claim that the increased WBC count is causing the infection or virus.

Getting back to the subject at hand, there are certain studies which indicate a correlation between depression and some neurochemical changes in the body – including neurotransmitter levels. However, in order to prove that these neurochemical changes are the cause of depression – rather than the result or cofactor of depression – the following would need to be true:
1. All people with those neurochemical changes have depression.
2. All people with depression experienced those neurochemical changes.
It turns out that neither of those variables are true. Many people with depression have normal or even high levels of serotonin, and many people with low levels of serotonin are not depressed. This suggests that when there is a correlation between depression and low serotonin levels in the scientific literature, the low serotonin levels are either a result of the depression or a coincidentally occurring co-factor.
Charley on December 14, 2008 at 2:16 pm

It seems that we need a definition for “Depression”. Define “Intelligence” for example – do all intelligent people have large brains? Is there any characteristic that is 100% uniform among all “intelligent” people?

Are there different types of intelligence that can be measured in different ways?

Can different types of intelligence be observed objectively? e.g. a PET scan?

What we here are calling “depression” might be 100 different things. Like “headache”.

Do all people with headaches have dehydration? No. Do many? Yes. Are many people helped by drinking water? Yes. Are all headaches fixed by drinking water? No.

Maybe this argument has lost it’s meaning?
Chris on December 14, 2008 at 2:53 pm

Charley,

I agree that we need a better definition for depression. One of the problems with that is that the definition has become less and less specific over time, and more and more inclusive of the shifting moods and feelings that one could expect to experience in a normal human life.

For example, in the latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), a person is allowed precisely two months of grief after the passing of a loved one. After those two months are up, if the person continues to grieve they are then labeled “clinically depressed” and presumably become candidates for medication.

And that’s exactly the point. Pharmaceutical companies are actively involved in redefining depression and creating entirely new conditions out of thin air (i.e. premenstrual dysphoric disorder) in order to expand the market for antidepressant drugs. A former CEO of Merck famously remarked that his dream was to sell his drugs to healthy people, since that was by far the largest market of all.

30 million people take antidepressants, and yet only 12-14 million have a diagnosis of clinical depression. Of that 12-14 million, I would suggest that only a small percentage have a truly entrenched depressive disorder that is not responsive to changes in diet and lifestyle and psychological or spiritual work.

I agree with you that the term depression has become so diluted that it is, in practice, almost meaningless. But keep in mind that diagnosis is the basis for treatment. In modern Western medicine, treatment means drugs or surgery. The only way pharmaceutical companies will sell more antidepressants is to expand the number of people that are labeled as depressed, or to expand the number of conditions that can be treated with antidepressants. They are vigorously involved in both strategies.

What if we didn’t rely so much on the term “depression”? What if a patient came and reported their feelings and experience to their doctor without even using that word? What opportunities would open up for treatment if both the doctor and the patient let go of the idea that the patient is “depressed”?

In my experience with depression, I’ve found that the term “depression” closes doors rather than opening them. It can discourage us from inquiring more deeply into the state we so readily label as “depression”, and it can create a powerful “story” about ourselves that, in my opinion, obstructs rather than promotes healing.

I have a friend who committed suicide. I spent time with him before he took his own life. The thing that ultimately pushed him over the edge, I think, was the idea that he was a “depressed” person and would have to struggle with depression for the rest of his life. That was too much for him to bear.

There is no such thing as a “depressed” person in the sense that there are tall people, white people or left-handed people. There are only people who are experiencing feelings that we label as “depression”. For what purpose? Part of the reason is to try to help them, but another part is to sell more drugs. In either case, however, I think the label of depression does more harm than good.
Michael Etts, LMSW on December 18, 2008 at 11:58 pm

There is a great deal of evidence to show that trauma causes structural changes in the brain and subsequent behavioral changes. Most are animal studies but recent brain imaging technology shows human brain changes. If you go here, http://www.lawandpsychiatry.com/html/hippocampus.htm , you can see pictures of how the hippocampus is damaged (shrunken) in people with PTSD. From my own paper, “Early childhood and the ability to cope with trauma”, highlights from animal research:

[…] pups of stressed [rat] mothers […] were more fearful and irritable and
produced more stress hormones. […] prenatally stressed monkeys […]
result[ed] in a wide range of impairments including neuromotor
difficulties, diminished cognitive abilities, and attention problems.
[…]
Researchers hypothesize that a mother’s stress hormones can damage
the developing brain of the fetus. Very recent research shows that
maternal stress hormones released during pregnancy may adversely
affect human fetal brain development (Stien, Kendall, 2004, pp. 21-22).

Also, from the blog of a psychiatrist called “How do anitdepressents work?”, (http://fdlpsychiatry.com/blog/?p=35), this quote:

Earlier studies have shown effects of SSRIs on neurons in the hippocampus, an area of the brain involved in memory and emotions– SSRIs increase the ‘volume’ if this structure in animals, and also affect the degree of branching of dendrites, the receiving-portion of neurons, in this part of the brain. During stress the dendrites in this region lose their complex branching pattern, and antidepressants restore the branching pattern, in essence having a neuroprotective affect during severe stress.

The pun is intentional; the chemical imbalance theory is clearly imbalanced.

Finally, I agree that the label “depression” is both deceptive and harmful. I think a better description would be post traumatic grief
Charley on December 19, 2008 at 7:12 pm

Thanks for this Michael – I had an argument in a therapy group one evening a long while back. I said that obsessive thoughts and behaviors could cause “brain damage” – and I was nearly laughed out of the room. I wasn’t quite able to back it up, but I knew I’d heard evidence of it.

I just sent this link to the the psychologist in charge of that group.
Toby on December 19, 2008 at 7:16 pm

As learned as the above seems, I have to take issue with the previous post.

Functional MRIs do indeed show that the brain is changing by measuring blood flow in the brain. But flow patterns change constantly during the day — this is true for everyone. What brain scans do is take a “picture” of what the brain is doing in that particular moment. This is not a static thing.
Furthermore you state that the hippocampus is shrunken for people with PTSD. Are you diagnosing PTSD on the basis of a shrunken hippocampus? If you are, you have crossed the boundary from psychiatry into neurology.

Or, as I assume, have you taken a social construct known as PTSD that has never been proven to be a medical disease, “diagnosed” people with it and then measured their brains? This would be a fundamental error in logic — a circular argument.

As far as the quote about dendrites is concerned, I have read so many of these conflicting psychiatric studies that I am skeptical of the veracity this claim. But let’s assume for the moment that this is true, that SSRIs really do restore the branching patterns of dendrites in the brain.

We also know from meta-analyses of all clinical studies submitted to the FDA (Kirsch 2008) that SSRIs are statistically no more effective in patients than placebo.

Does this mean that placebos restore the branching patterns of dendrites, too?

Might there be any other non-drug options without the severe short and long-term side effects of SSRIs that can restore these patterns? Seems like this might be a more worthwhile investigation, albeit less profitable.

Which brings me to my thesis: Contrary to what we may all read in the mass media, there are many folks (including me) who do not believe that human psychology is medical. How else do we explain the placebo effect, “mind over matter,” and a host of medically unexplainable human mind abilities?

In boiling us down to hippocampi and dendrites, biological psychiatry is doing us a huge disservice. It tells us that we are servants of our bodies, hopelessly subject to the whims of nature and nurture.

This is not to slight those who have been traumatized by events in their lives. Rather it is to suggest that it is not their brains that are causing their trauma but something within themselves that they can eventually master.

Fortunately, this opens the door to some real, permanent solutions.
Charley on December 19, 2008 at 7:37 pm

Nobody is going argue that, at best – at it’s most optimistic and hopeful best, that psychiatry is even close to an imperfect science, let alone a “real” one -

You are comparing apples and oranges.

PTSD is a convenient name for a group of symptoms in patients who share similar events in their history. Nobody is saying PTSD is an illness like bone cancer or syphylis.

As for the constant, and unrelenting onslaught that all people suffering from the symptoms of mental illness can “master something within themselves” – this is the SAME argument and you are contradicting yourself. WHAT evidence shows this to be true?

If you have high triglycerides in your blood – what exactly does THAT measure? It could be lots of things, yet the doctor will tell you it is because you eat a bad diet without even taking pause to measure what you eat. Is that science?

EVERYTHING about our existence is physical my friend. Every thought in your head, down to the lowest function of your body is governed by physical processes.

Are you saying you can control all of them through positive thinking? Do you have proof?

So why is the concept that there may be measurable and treatable parts of mental illness trouble you so much?

Sure there is an easy market to sell a pill. Sure doctors can be lazy. Sure people want an easy way out. Agreed. But this does not make your argument.

If you take PTSD subjects, and you compare such data as this against a similar sample of “normal” people, and you find significant structural diffeences – this is not a circular argument. It is science. The shrunken hippocampus in this image is NOT caused by “daily flucuations”. If your brain mass changed that much in a day, you’d be dead or in a coma at best. I used to work in radiology. I’ve seen scans.

I’m listening to both sides of the argument here – but…
Toby on December 20, 2008 at 12:23 am

Charley, I think we both agree that psychological and emotional problems can come from a wide variety of sources. Some can be physical: measurable ailments such as encephalitis or Lyme Disease, extreme allergies, vitamin or mineral imbalances, and so on. These are treatable.

What I am against is the use of psychotropics to handle so-called “chemical imbalances of the brain,” which I think we also agree is a myth.

Brain scans are useful for picking up tumors or lesions which also may cause mental problems. Again, these are valid physical problems that must be checked and verified before an effective handling can be done.

But the problem with biological psychiatry is that it attempts to address “disorders” that can’t be proven to exist as a provable, testable medical pathology — such as “depression” or “bipolar” or “PTSD,” which are then treated with very strong chemicals that can cause dependency and severe side effects.

You have mixed together the two separate arguments from my last post.

Let’s start with the brain scan. Because patterns or blood flow change so much during the day, brain scans simply cannot give a reliable indication of any kind of “mental disorder.” [Also, brain scans follow the "chicken and the egg" argument: does brain function cause behavior or does behavior cause brain function? Can't be proved]

As for my other point — “PTSD” is yet another arbitrary psychiatric diagnosis that can’t be proven. I think we both agree that it is a convenient name for a very wide variety of psychological and emotional complaints — and not a medical disorder that can be proven as a pathology. Therefore, the claim that a shrunken hippocampus ”causes” PTSD is simply unfounded. A link is not a causation but a correlation. The argument is circular because you are presupposing the existence of PTSD in order to prove it exists.

If you can prove to me definitively that the broad category known as PTSD is caused by a shrunken hippocampus, I will agree with you, and then we can set about to fixing the problem. You’ll have to pardon my cynicism, though, but this “shrunken hippocampus” argument sounds suspiciously like another “chemical imbalance” sales pitch designed to sell psychotropics. If you’ll look through the psychiatric literature you’ll find literally dozens of other theories.

I must admit that we do differ on your statement that “everything about our existence is physical, my friend.” As I mentioned before, the human mind is capable of a great deal — witness the amazing ability to heal the body through the placebo effect or other such mind phenomena. Something observably does profoundly influence behavior above and beyond the physical organ called the “brain.” Freud believed this, for example, and up until recently this went unquestioned in psychology and even in psychiatry, until it was hijacked by the drug industry.

So in summary, yes, there are times when bad things happen or we get down for some reason we can’t understand. And if it is not provably physical and its true source directly treated, then we have a problem of a different nature. Instead of medicating it away, we need to find a way (using friends, relatives, counselors, whoever) to master it ourselves.
Chris on December 21, 2008 at 11:48 am

Hi Toby & Charley,

Thanks for such a fascinating dialogue! I’m away from home and have very limited internet access. When I return I’ll share some thoughts.

Happy Holidays,
Chris
Toby on December 22, 2008 at 3:42 pm

You’re welcome, Chris!

Charley’s viewpoint is very valuable because it helps me clarify my own.

I look forward to your weighing in on the subject.
Michael Etts, LMSW on December 22, 2008 at 6:28 pm

<!– /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:”"; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:”Times New Roman”; mso-fareast-font-family:”Times New Roman”;} p {mso-margin-top-alt:auto; margin-right:0in; mso-margin-bottom-alt:auto; margin-left:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family:”Times New Roman”; mso-fareast-font-family:”Times New Roman”;} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} –>

/* Style Definitions */
table.MsoNormalTable
{mso-style-name:”Table Normal”;
mso-tstyle-rowband-size:0;
mso-tstyle-colband-size:0;
mso-style-noshow:yes;
mso-style-parent:”";
mso-padding-alt:0in 5.4pt 0in 5.4pt;
mso-para-margin:0in;
mso-para-margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:10.0pt;
font-family:”Times New Roman”;}

Part of the reason I hesitate to write in an abbreviated manner is how much it leaves open to interpretation or more aptly, misinterpretation. My goal was to lend data and skepticism to the notion that psychological issues are due to a chemical imbalance. Toby, you made some extensions to what I said, none of which I endorse. I don’t think that PTSD can be diagnosed by an fMRI nor do I believe that it is primarily a medical condition. I do think that there are profound changes in the brain as a result of experience, traumatic and otherwise.
I completely agree with your statement that
In boiling us down to hippocampi and dendrites, biological psychiatry is doing us a huge disservice. It tells us that we are servants of our bodies, hopelessly subject to the whims of nature and nurture.
There is a great deal of evidence supporting theories of neuroplasticity. The case could be made that cognitive behavioral therapy could not work or would not work for long, without neuroplasticity. Therapeutic interventions should be the first approach for resolving any psychological issue and good therapy should be guided by neurological awareness, but not limited to it.
There are a huge number of behavioral and habit changes which a person can make, such as mediation, corrective experiences (usually experienced in therapy), self affirmations, good sleep hygiene, changing their attentional focus, NLP techniques, etc.
Based on your second post, I think we are in broad agreement. We are not victims of our brains but custodians and engineers. By using the power of choice, combined with evidence based techniques, we can exercise a great deal of control over the continued development and maturation of that gift we call the human brain.
<!– /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:”"; margin:0in; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:”Times New Roman”; mso-fareast-font-family:”Times New Roman”;} @page Section1 {size:8.5in 11.0in; margin:1.0in 1.25in 1.0in 1.25in; mso-header-margin:.5in; mso-footer-margin:.5in; mso-paper-source:0;} div.Section1 {page:Section1;} –>

/* Style Definitions */
table.MsoNormalTable
{mso-style-name:”Table Normal”;
mso-tstyle-rowband-size:0;
mso-tstyle-colband-size:0;
mso-style-noshow:yes;
mso-style-parent:”";
mso-padding-alt:0in 5.4pt 0in 5.4pt;
mso-para-margin:0in;
mso-para-margin-bottom:.0001pt;
mso-pagination:widow-orphan;
font-size:10.0pt;
font-family:”Times New Roman”;}

Charley, I think your intuitive theory has some good backing. First, it is estimated that internal dialogue runs at about 1500 words per minute, or 10 times the speed of speech (Wiley N (2006). Inner Speech as a Language: A Saussurean Inquiry. Journal for the Theory of Social Behaviour. 36(3), pp. 319-341). Combine that with the theory of learning that states neurons that “fire together, wire together” and you could make the case that by thinking the same thought over and over, you are strengthening that thought pattern. If you think of it like highways, the brain is paving “roads” where there is repeat traffic. It is reasonable to theorize that these 1500 word per minute inner conversations are widening those roads or thickening the pavement.

1 · 2 · Next ›

Even if fifty million people say a foolish thing, it is still a foolish thing.” – Anatole France

THE HEALTHY SKEPTIC is a blog dedicated to debunking mainstream myths about nutrition, health and disease. We bring you the latest analysis and research on a wide variety of topics to help you make educated and informed choices about your health. Make sure to sign up below to receive a daily email digest of our content!

The “chemical imbalance” myth

The history of the “chemical imbalance” theory

The fatal flaws of “chemical imbalance” theory

How have we been fooled?

Recommended resources

60 comments

Reply

Daily Email Digest

Archives

Categories

Recent Posts