Saul Marcus, ND - Naturopathic Doctor

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Serotonin, Depression and the Chemical Imbalance

The "Chemical imbalance" theory

In the 1950's and 60's it was noticed that some drugs help patients with feelings of depression. These were the monomine oxidase inhibitors (MOAI's) and tricyclic anti-depressants.

These drugs were thought to work by inhibiting the breakdown of brain neurotransmitters such as dopamine, serotonin, and norepinephrine. Therefore it was theorized that a defect in the brain's metabolism of neurotransmitters is the cause of depression.

Eventually new drugs, such as the the selective serotonin reuptake inhibitors(SSRI) largely replaced MOAI’s and tricyclics antidepressants. However these newer drugs are still thought to act the same way, by inhibiting the metabolism of certain neurotransmitters.

SSRI drugs, mechanism of action

Nerve cells talk to each another through chemical messengers called neurotransmitters.

Neurotransmitters are released into the space between nerve cells called synapses. There it is sensed by the dendrite of a neighboring cell and the message is received.

Eventually the neurotransmitter is absorbed back into the nerve cell. This is called reuptake.

SSRI's are thought to work by stopping the reuptake of neurotransmitters from the synapse. This is is why they are called “reuptake inhibitors.” In theory this leaves more neurotransmitter in the synapse and thus strengthens communication between nerves cells.

In truth, this is a sales pitch patients and not proven scientific fact.

All medications have prescribing guidelines which can be easily looked up online. The guidelines for the psychiatric drug Cymbalta can be found here.

It states as follows:

Although the exact mechanisms of the antidepressant, central pain inhibitory and anxiolytic actions of duloxetine in humans are unknown, these actions are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. [1]

Besides stating outright that the mechanism of action is unknown, the guidelines then says the drugs actions are "believed" to be related to serotonin and noradrenaline. What exactly is is meant by "believed." Does this mean that maybe the drug works this way? That they guess this is what it does?

The prescribing guidlines for Proazac can be found here.

it states as follows:

Although the exact mechanism of PROZAC is unknown, it is presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.

What is meant by "presumed." Does this mean that they don't know, so they just assume this is how the drugs works?

Anyone can go online and download the prescribting guidelines for any so called SSRI and they will all use vague language to the same effect. This is because it's not known what these drugs are doing or how they work.

Of course a medication, nutritional supplment, herb, or any therapy can work through multiple mechanisms which are not all understood. For example, getting a massage may be helpful for depression even if all the mechanism of action are not fully understood. The problem with psychiatric drugs aret:

  • These are very dangerous mediciations with numerous side effects, and since no one knows how they work, a science experiement is being run each time they are prescribed. There is no evidence that psychiatic medications correct a "chemical Imbalance." However, if they did that, then there should be multiple side benefits, not long lists of "side effects."

  • The drugs are sold under in order to correct a "chemical imablance." But there are no tests for the "chemical imblance" or reason to assume that mental symptoms are caused by one.

Why depression is not caused by a serotonin "chemical imblance"

Research simply does not back up the serotonin "chemical imbalance," theory. The following quotes from professional journals are not unique. This is just a small examples of what the experts say to themselves:

From the article - Neuroimmune mechanisms of cytokine-induced depression

The current diagnostic categories for depression ... are not etiologically or biologically has been proposed that “depression”, likely reflects multiple pathogeneses. As we move toward a better biological understanding of depression-related symptom constellations or syndromes, the term “depression” may prove inadequately broad. [2]

From the article -

Contemporary neuroscience research has failed to confirm any serotonergic lesion in any mental disorder, and has in fact provided significant counterevidence to the explanation of a simple neurotransmitter deficiency. Modern neuroscience has instead shown that the brain is vastly complex and poorly understood [...] to propose that researchers can objectively identify a “chemical imbalance” at the molecular level is not compatible with the extant science. In fact, there is no scientifically established ideal “chemical balance” of serotonin, let alone an identifiable pathological imbalance.

[...] the claimed efficacy of SSRIs is often cited as indirect support for the serotonin hypothesis. Yet, this ex juvantibus line of reasoning (i.e., reasoning “backwards” to make assumptions about disease causation based on the response of the disease to a treatment) is logically problematic—the fact that aspirin cures headaches does not prove that headaches are due to low levels of aspirin in the brain. [3]

Making sense of the "scientific" research

The serotonin theory is too simple. Depression can not be reduced down to one factor.

Our mood is of course related to brain biochemistry. But biochemistry is determined by a myriad of environmental factors. So discovering biochemical markers wouldn't necessary tell is why they are off.

causes of depression: chornic infection, physical and emotional trauma, nutrition and toxicity. These effect mood and brain biochemistry.

Even if some biochemical test was discovered, and it was shown serotonin was definetly invovled in depression, would this be clinically relevant?

No, for this would simply beg the questions "why is serotonin low?"

Naturopathy works off of the concept that the body wants to be healthy. Symptoms (including depression) have a logic of their own.

Why would the body ever actually want to produce depression?

At certain times depression may function as a self protective mechanism. These are some examples:

  • In times of chronic illness, depression can cause someone to go into a "hibernation" mode, preserving energy.

  • In situation like PTSD, depression may make someone more reserved. They will tend to avoid situations that their body has been taught is dangerous.

When the body is assaulted by physical (or emotional) toxins, a change in biology which relfects depressed mood, can be considered an adaptive response. Compentant, and compassionate health care should be patient focused, and help the person release the toxin.

In a very real way, emotional trauma can be considered another form of toxin. Emotional trauma affects how we feel and how our body functions. There are numerous healing techniques which can help patients release negative emotions such as: talk therapy, homeopathy, flower essence, NET (neuro-emotional technique).

So even if emotional trauma triggers a "chemical imblance," in the brain, where is the logic in blaming the brain for causing depression?

What do drugs for depression really do?


Most participants described a general reduction in the intensity of all the emotions that they experienced, so that all their emotions felt flattened or evened out, and their emotional responses to all events were toned down in some way. Very common descriptions of this phenomenon included feelings of emotions being ‘dulled’, ‘numbed’, ‘ flattened’ or completely ‘blocked’, as well as descriptions of feeling ‘blank’ and ‘ flat’. [4]

The study goes onto describe reduction in both positive emotions (those associated with feeling good) and negative emotions (those associated with feeling bad).

So while the anti-depressants seemed to work in controlling patients negative emotions, they seem to do this by flattening out all emotions in general.

But is this really a healthy response? If medications truly corrected a "chemical imbalance" they should be expected to improve brain function, not impair it. Also, something in the case of emotional trauma it's important for people to work through it. This could be done in safe environment with a therapist. How does taking an agent which deadens emotions helpful?

How well do anti-depressants really work

Some people feel much better on anti-depressants, and some feel much worse. Meta-analysis of multiple studies show that for mild depression anti-depressants are no better placebo. Interestingly, the research does show more improvement for those people who have worse depression.

, the article; Initial Severity and Antidepressant Benefits: a Meta-Analysis of Data Submitted to the Food and Drug Administration.

"Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance. Yet, the efficacy of the antidepressants may also depend on the severity of initial depression scores." [5]

Even if someone feels better on anti-depressants, this doesn't mean it was the healthiest option. Besides having numerous side effect, anti-depressants seem to work by numbing emotions overall, and not improving the health of the brain. Supressing negative emotions should not be confused with improving health and correcting the actual cause of those emotions.




[1] Cymbalta prescribing guideliens.

[2] Loftis, J. M., M. Huckans, and B. Morasco. "Neuroimmune Mechanisms of Cytokine-induced Depression: Current Theories and Novel Treatment Strategies." Neurobiol Dis 37.3 (2010): 519-33. Print.

[3] Lacasse JR, Leo J (2005) Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392. doi:10.1371/journal.pmed.0020392

[4] Jonathan Price, Victoria Cole, and Guy M. Goodwin. Emotional side-effects of selective serotonin reuptake inhibitors: qualitative study BJP September 2009 195:211-217; doi:10.1192/bjp.bp.108.051110

[5] Kirsch, Irving, Brett J. Deacon, Tania B. Huedo-Medina, Alan Scoboria, Thomas J. Moore, and Blair T. Johnson. "Initial Severity and Antidepressant Benefits: a Meta-Analysis of Data Submitted to the Food and Drug Administration." PloS Medicine. Web. 05 Feb. 2011. <>.