You've heard that depression is due to a chemical imbalance and that the chemical imbalance in question is the neurotransmitter serotonin?  You've probably heard it from commercials, your doctor, talk shows, sitcoms and in casual conversation with friends and family.

Antidepressant use increased almost 400% from 1998 through 2008. It’s now the third most common prescription for all age groups.  About 60% of Americans have taken antidepressants for more than two years, 14% of them for more than 10 years.

Some breaking research that got swept under the rug in the media a couple of years ago has to do with depression and the SSRI class of medications used to treat depression.  These may sound familiar by name:  Celexa, Zoloft, Prozac, Lexapro, and Paxil to name a few. 

What if the serotonin-depression connection is complete garbage and therefore taking medication to increase serotonin is nothing more than a placebo effect?  That's what was discovered and reported in 2022 in Molecular Psychiatry.

"Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress."

But where did this "common knowledge" come from?  And why has disability due to depression increased as we have increased access and usage of medications used to treat depression?  Shouldn't we have less depression with more medical intervention?  Things that make you go hmmm.

Let's take a look at three things surrounding this topic of serotonin and depression. 

In the 1950s and 1960s, the infectious disease tuberculosis was very feared.  Of all infectious diseases, tuberculosis remains one of the most deadly worldwide. TB is a contagious lung disease caused by bacteria and passed through the air from an infected person to others due to poor conditions of sanitation, nutrition, and hygiene.  Due to the death toll of TB, drugs were developed as fast as possible. 

During that time, there were observations on the unintended positive mood-altering effects of anti-TB medications.  These anti-TB meds appear to make people happier.  Why?  They were thought to interfere with the MAO enzyme.  No, not the former leader of China.  

MAO (Mono-amine oxidase) is an enzyme that involves removing neurotransmitters from your brain such as serotonin, dopamine, and epinephrine.  If this enzyme is being inhibited (the theory behind why anti-TB drug's impact on mood), then they reasoned that depression must be a deficiency in these brain signals.  Hence, the serotonin-deficiency, chemical-imbalance messaging started.   If these brain signals are staying in the brain longer and people are in better moods, then we could develop medications to keep these brain chemicals around longer.

Was there any testing to confirm this hypothesis?  Nope.  They just ran with it.  What's the problem with the deductive conclusion of this logic? 

Let's apply it to something else.  Let's say you have social anxiety, but you notice that if you have a few cocktails before heading to the social function, you do great and have a blast.  You could deduce that social anxiety is just a lack in beer, wine, or spirits.  Therefore, to "manage" your social anxiety, you have to consume 2-3 alcoholic beverages daily to make sure you don't relapse. 

What could go wrong?

Much like the "cholesterol-heart disease" hypothesis that can't be questioned, the "serotonin-depression" hypothesis was questioned through the decades but anything that challenged it was essentially disregarded. 

There have been studies where there was no difference in depression symptoms vs happiness with the same low levels of serotonin.  There have been studies where they deplete tryptophan (the building block of serotonin) and the participants did not develop depression.  There have been studies where an INCREASE in serotonin has shown more depression.  

In 2008, the New England Journal of Medicine dug up the studies used for the 12 FDA approved anti-depressants.  They had to obtain these via the Freedom of Information Act.  There were 74 total studies used for those 12 antidepressants. 

38 of those 74 studies claimed a positive outcome, whereas 36 claimed a negative outcome.  But that's not what was published.  Of these 36 negative studies, 3 were actually published as negative, whereas the remaining 33 were either NOT published (22 studies) or were published as positive (11).  

What happens when a person is given an anti-depressant by their doctor and it's not working?  They are given more as adjuncts to the first.  What if someone feels better on an SSRI?  They could have a serotonin issue, but with the research, it seems 50/50 at best.

That leads to questions of "what's at the root of depression?" What if we're looking at depression from the wrong perspective?

What if we changed the narrative around depression as being a disease diagnosis and instead put it in context that depression is actually an intelligent adaptation to buy you enough time to SLOW DOWN and deal/heal with the underlying root cause of what is trying to shorten your life? 

What if it's more of a psycho-neuro-endocrino-immunulogical adaptation?  Yup, that’s totally made up.  I also know it's easier said than done.  

What I also know and have seen in my clinic is that serotonin and other neurotransmitters are released and activated based on what your nervous system tells them to do.  This model of depression looks at the culmination of a number of different disturbances from trauma, nutrient deficiencies, oxidative stress, dysbiosis, and cell respiration to name a few, to treat you as a person and system and not merely a diagnosis or symptom.  Therefore, I challenge you to look at depression as having the same roots of dysfunction as other ailments like fatigue, Alzheimer’s, heart disease, osteoporosis, diabetes, etc. 

A couple of great books to dive into this on your own and challenge your perceptions of depression are:

1. A Mind Of Your Own by Dr. Kelly Brogan 

2. Brain Energy by Dr. Chris Palmer