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.


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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 Tales.  The 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.