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Showing posts with label chemical imbalance. Show all posts
Showing posts with label chemical imbalance. Show all posts

Thursday, June 8, 2023

The Conflation of Chronic Sadness With Major Depression



When I bring up with many other professionals the idea that major depression is now over-diagnosed by relabeling what used to be called dysthymia as "mild' major depression, a lot of them seem to disagree. Or they just tune out. “That’s just your opinion,” I might hear. Well, luckily the DSM-V now provides evidence that I am on the right track. In the DSM-V, the term “dysthymia” has been replaced! It is now called Persistent Depressive Disorder

As I have discussed in many previous posts, my opinion about major depressive disorder is that it is more of a brain disorder than mere unhappiness. The word depression itself is a symptom, not a disorder. It is in the interest of drug companies to conflate chronic psychological unhappiness with major depression so they can sell more antidepressant drugs to people who will not actually benefit from them.  Now,  it is also possible to have both, which is called double depression.

While many of the criteria are the same for the new diagnosis as the previous criteria for dysthymia, there are subtle differences that obscure the difference between that disorder and major depressive disorder. In a percentage of people with the latter disorder, it may become chronic. This is seen in the new definition of the disorder, which reads “This disorder represents a consolidation of DSM-IV-defined chronic major depressive disorder and dysthymic disorder. These disorders should not be consolidated.

There is one additional change which is telling. The only specific criteria for the disorder that has been changed has gone from “The disturbance is not better accounted for by MDD or MDD in partial remission” to “Criteria for Major Depressive Disorder (MDD) may be continuously present for 2 years, in which case patients should be given comorbid diagnoses of persistent depressive disorder and MDD."  Double depression has nothing to do with the length of the major depressive episode.

Drug companies have enlisted academic psychiatrists to become “key opinion leaders” in order to push this idea, and have even advocated the use self report surveys designed to screen for major depression (therefore having a lot of people test positive who don’t really have the disorder  – false positives) as diagnostic instruments.

This has led to a host of articles in the popular press that seem to indicate that antidepressants are nothing more than placebos. Nothing could be further from the truth, but a lot of psychiatry critics like Robert Whitaker have seized on “research” articles (which do a crappy job of making the correct diagnosis) that seem to show this to be the case.  After all, since most anti-depressants are generic,  it's better for drug companies' bottom line if instead of those drugs, expensive new anti-psychotic drugs can be recommended instead.

The critics also use the fact that we don’t know exactly what causes major depression to dismiss the whole diagnosis. The incorrect hypothesis that the condition is due to a “chemical imbalance,” which is sometimes advanced by clinicians, must mean that it is not a real disease. Dumb. Clinicians have often used this oversimplified idea to convince resistant patients to take the medications. Researchers rarely if ever actually said that a chemical imbalance was the cause of the disorder.

Of course, it’s not always easy for clinicians to tell the difference between dysthymia and major depression in a given patient, but in most cases it’s fairly straightforward.  There is nothing that stops anyone from being chronically unhappy when they are not having an episode(the euthymic state) of major depression. And major depression is episodic with normal-for-them baseline mood periods in between episodes.

A good clinician will define a response to antidepressants as good if the patient returns to their baseline. They don’t have to be in a good mood to have had a good response, but may just need psychotherapy like any other dysthymic patient. Nonetheless, many of these patients who have double depression are mislabeled in the literature as “treatment resistant,” which means that docs are encouraged to add still more drugs to antidepressants to “augment” them. There are of course patients who actually are treatment resistant and need this augmentation, but in my 45 years of practice this was a relatively small contingent.

Briefly and in an oversimplified manner, distinguishing the two disorders has to do with the “three P’s” – persistence, pervasiveness, and pathological. (You can tell if a study employs the correct definitions by seeing how the diagnosis was made with their subjects. The P’s are emphasized in an excellent diagnostic interview called the SCID). Persistent: this is the duration criteria. An episode has to last at least two weeks. Admittedly, the two-week criteria is arbitrary, but is put in so clinicians don’t make the diagnosis after too short a period.  The “everything is bipolar” crowd routinely poo poo's the duration criteria.

Pervasive: the symptoms have to be present nearly all day every day no matter what goes on in a patient’s life. This means that if a patient were to win the lottery, it wouldn’t cheer him up all that much.  Pathological: this means that the ways that the patient reacts to any stress is different from the way they might react if they were not in an episode. See the lottery statement. Also, if a lover were to, say, break their heart, this would not always make a whole lot of difference in how bad they feel.

These issues are not seen with good doctors, who not only know how to take a complete bio-psycho-social history but actually still do them.


Friday, May 20, 2011

The False Theory That Refuses to Die


"The great tragedy of Science — the slaying of a beautiful hypothesis by an ugly fact."  ~ Thomas Huxley

The presence in the brain of a "chemical imbalance" is one theory about the cause of certain mental illnesses. Specifically, the basic concept is that neurotransmitters -  the different chemicals that are released from the ends of brain cells into the space between two neurons (synapses) and are the means by which two neurons communicate - are out of balance within the brains of patients suffering with clinical depression or schizophrenia. Therefore, medication which helps these conditions must surely correct these "imbalances."

In the case of clinical depression, two neurotransmitters are thought to be the primary culprits. Because antidepressants increase the amount of serotonin and norepinephrine in synapses, these monoamines or catecholamines - different name for the class of chemicals in which they are classified - this was presumed to be the mechanism of action through which the drugs helped depressive symptoms.

Zoloft Ad

Research into other mental illnesses such as schizophrenia also found that too much activity of certain neurotransmitters such as dopamine was correlated with these disorders.  The basic problem with this theory is that it is wrong. There is no evidence that a "chemical imbalance" is behind serious clinical depression. 

A few problems with this idea: 

First, the effect of antidepressants on serotonin and norepinephrine in the brain is immediate, but the therapeutic effects do not begin to appear until after about a week and a half pass by, and the full effect takes 3-6 weeks.

Second, all of the drugs affect the monoamine neurotransmitters, but some people respond to one but not another, while others do not respond to the first but do to the second.

For a third point, I quote neuroscientist John J. Medina, author of the wonderful Molecules of the Mind column in the Psychiatric Times.   From his April column: 

"When we consider the molecular mechanisms of SSRI interactions, it is easy to resort to commonly taught ideas about interactions that involve a single synapse.  Nothing could be further from the truth. 

The most comprehensive neurological view of SSRI actions must take into account the participation of thousands of individual neurons strung together in coordinated, complex neural networks.

And not just serotonergic neurons.  The cells are in contact with many other central nervous denizens, from adjacent glial cells to the extracelular matarix into which the cells are embedded."

And yet, the monoamine theory refuses to die!  "Biological" psychiatrists have become obsessed with monoamine neurotranmitters and the parts of the neurons which snap them up and react to them - the neurotransmitter receptors. I think that horse has been beaten to death.  Studying receptor physiology will, I predict, not lead to any new drugs with a different mechanism of action from the ones we have now.


The propaganda coming from Big Pharma continues to push the importance of the neurotransmitters and their receptors, even when the significance of many findings of receptor differences is completely unknown.  A recent ad that does this is discussed in Dan Carlat's blog.

For one thing, these monoamines make up only about 5% of all neurotransmitters in the brain.  For another, all the other ones, most notably glutamate and GABA, all regulate each other in a cascade of two-directional influences among thousands or even millions of cells. Last, all neurotransmitters are widespread throughout the entire brain.

Now do not get me wrong.  Just because one theory about how antidepressants work is wrong, this does not mean that the drugs do not work.  Clinically, in properly diagnosed patients, they work fabulously.  I have personally witnessed their dramatic positive effects in literally thousands of patients.

There are other reasons why recent studies seem to show that antidepressants do not work in moderate to mild depression (NO honest study says they do not work in severe depression). Not the least of these reasons is that the drugs have mostly gone generic and Big PhARMA has a vested interest in seeing other, less effective drugs being used.  See my 8/31/10 post, SSRI TalesThe drug company marketing departments are so sophisticated that they use the anti-psychiatry zealots to help them sell more (and more dangerous) brand named drugs!

To those that think antidepressants never work, I have one word for you:  Bullsh*t!

For ages, we did not know how aspirin works.  I am not sure that we really do now.  But it relieves an awful lot of headaches for sure.