SSRIs and Depression


I believe that SSRI’s do work to help with depression. But recent research shows that it works in different ways than originally assumed. Detailed research can be seen further down on the page.

Note A LOT more references will be listed in here in future.

But basic data can be found right here:

Side Effects

Since serotonin does not directly correlate to depression, some have theorized that these “secondary” effects or side effects of the medication could be the actual mechanism of action that allows the medication to work.
All hormonal and neurotransmitters that have been proven to be affected by antidepressants will be listed below, including serotonin.
Most of the things stated will not be speciic to a certain medication. There will be a chart added later to help identify which specific medications affect which specific parts of the body and the significance of that effect.

List of Effects

  1. Serotonin – increase
  2. Dopamine – same or decrease in most cases (except sertraline and bupropion)
  3. Oxytocin – increase
  4. Brain-Derived Neurotropic Factor (BDNF) – increase
  5. Estrogen – increase (in female)
  6. Testosterone – decrease (In male and female)
  7. Insulin response – improved
  8. Cortisol – decreased response
  9. Vasopressin (ADH) – slight decrease
  10. Hunger – due to increase serotonin as serotonin is found in large amounts in the stomach and actually control the rate at which muscles cause food to pass thru the stomach
  11. Masked H. Pylori infection – see effect 5 and consider that estrogen suppresses H. Pylori
  12. Nitrix Oxide – decreased ability to synthesis
  13. Zinc – increases usage rate and likely decreases stomachs ability to absorb zinc from dietary sources



The information is made public simply due to the important and possible benefit it may have.

SSRI medication do work for some individuals and for others it does not. This article attempts to provide a brief explanation as to why that occurs and some of the various methods that these medications use to improve the mood of those who take them.

This article is NOT written purely from a factual standpoint and attempts to look at all research regarding SSRIs, their side effects, their mechanism’s of action, and how some of the unintended side effects could be the true reason that they work.

No outside influence has affected this written and personal bias has been removed when evident and otherwise if bias is present it will be openly stated.


SSRI medications have actually confused the medical community since they were first developed in the 1980s. This is because several studies have failed to show a DIRECT CORRELATION between serotonin levels and depression. Yet when clinical trials of SSRI medications were conducted, they all showed an improvement in mood and depressive symptoms in both animal and human studies.

It is very common when reading through medical literature to see statements such as this:

“Treatment with SSRI’s had shown significant changes in clinical conditions [of depression]. However these changes did not relate significantly with serum serotonin levels.” ​1​

Now you may be wondering:

“If depression is not directly caused by serotonin then why does the FDA allow the medication to be sold?”

This because:

The FDA does NOT ask WHY a drug works.

Again, the FDA does NOT require that drug manufacturers or healthcare professionals know or understand WHY or HOW a drug works.

The FDA ONLY requires that companies do the following:

  • Demonstrate that the drug works as intended to treat the medical condition that it was designed to treat
  • That the benefits of the drug outweigh the risks.
  • Provide a reasonable theory of why the company believes the drug works

While this can be disconcerting, consider this:

  • Drugs already take 10-20 years in the US to go from concept, to study, to FDA, to doctor knowledge, to practical use.
  • If the question of WHY had to be answered, a lot few their medication would be available to doctors to treat their patients.

While it is NOT ideal, it is the best systems we have so lets work with it as we continue learning about SSRIs.

Often when data is presented that attempts to claim depression is solely and directly connected to serotonin levels it is often tainted data that comes from a corporation that has financial interest in that theory.

Depression is commonly gauged using symptoms and self-reported patient questionnaires. When comparing depression scores to serotonin levels, the high depression score did not directly correlate to lower serotonin levels (when compared to the control group).

To understand why this occurs lets look back at when serotonin was first theorized to be the cause of depression.

In the 1960’s the Serotonin Theory of Depression emerged (aka the monoamine hypothesis) which hypothesized that depression was only caused by an imbalance of serotonin in the brain. Shortly after this hypothesis was released to the medical community companies began to attempt to create medication to treat depression according to this hypothesis, these medications are referrered to as Selective Serotonin Reuptake Inhibitors (SSRIs). ​1​ In 1987 Fluxotene was approved by the FDA and in the ensuing years drug companies began to pump out new medications

  1. 1.
    Saldanha D, Kumar N, Ryali V, Srivastava K, Pawar A. Serum Serotonin Abnormality in Depression. Med J Armed Forces India. 2009;65(2):108-112.
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