By Jefferey Jaxen

The headlines have rung like a bell through popular culture and a public with fleeting trust in a medical-industrial-complex. A once sacred cow, settled science in the industry was that depression’s cause was a brain chemical imbalance problem. The chemical?….Serotonin – and Big Pharma’s decades long answer was a class of chemicals called Selective Serotonin Reuptake Inhibitors (SSRIs). 

During the 1950’s, and more intensively in the 1960s, a serious search for the molecule behind depression was ongoing. Despite no consensus on the antidepressant-like effects of the serotonergic theory, based on a deficit of serotonin in certain brain regions, several drugs were introduced on the market after 1957. 

One supercharging effect happened when the pharmaceutical company Eli Lily, eventually of Prozac fame and fortune, created their ‘serotonin-depression study team’ in the early 1970s. The results were predictable with the eventual creation of Prozac leading the world on a wild goose chase for the elusive serotonergic phantom.

A popular selling point of these newer class of drugs was a lower adverse event profile. However, since its approval, a laundry list of harms are now associated with SSRI drugs and particular, Prozac.  

The US Food and Drug Administration approved Prozac in 1987

With Prozac becoming the first approved SSRI, it quickly became one of the most prescribed antidepressants in the world racing Eli Lilly’s worldwide annual sales to the $2 to $3 billion range. Its patent expired in 2001 and the rise of competition from other pharmaceutical companies hit like a hungry wave to chomp away at a red hot SSRI market share.  

Edward Shorter writes in the British Journal of Psychiatry in 2014, “The uptake of Prozac became almost a cultural phenomenon, comparable with the fashion for high protein and low-carbohydrate diets to lose weight: ‘Washington City full of Prozac’, headlined the New York Times in 1994 City full of Prozac. Just imagine. I am not aware of comparable historical claims for any other pharmaceutical agent, penicillin included.

Shorter explains the reasoning for this meteoric rise writing, “How do we account for this success? It was partially a result of relentless marketing, undertaken with an intensity not hitherto seen in pharmaceuticals. By 1993, Lilly had 1600 sales representatives in the field in the USA, surpassed only by SmithKline Beecham’s 1800 reps for Paxil…”

Pump the breaks…hard.

Just published in the Journal Molecular Psychiatry, The serotonin theory of depression: a systematic umbrella review of the evidence looks at the principal relevant areas of research on the still influential serotonin hypothesis of depression. 

The researchers write, 

“The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.”

The authors conclude: 

“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.”

The researchers leave readers with this final paragraph in their analysis: 

“This review suggests that the huge research effort based on the serotonin hypothesis has not produced convincing evidence of a biochemical basis to depression. This is consistent with research on many other biological markers. We suggest it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.”

It is important to note that their study did not look at the effectiveness of antidepressants directly. Meanwhile, a companion article written by two of the study’s authors and published in The Conversation states,

It is important that people know that the idea that depression results from a “chemical imbalance” is hypothetical. And we do not understand what temporarily elevating serotonin or other biochemical changes produced by antidepressants do to the brain. We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe.”

The statement sent shockwaves through the egos and pocketbooks of SSRI cheerleaders everywhere causing The Conversation to take swift action publishing the article titled Depression: low serotonin may not be the cause – but antidepressants still work

the very next day.

Despite grabbing worldwide headlines, many in the scientific community came out after the research was published to claim they already knew about the debunked serotonin hypothesis. 

Meanwhile, the public has been left to still belief the leftover ‘chemical imbalance’ propaganda never fully corrected or atoned to by the collective professional body of psychiatrists. To add more confusion to the mix, psychiatrists still regularly dole out large numbers of SSRI prescriptions and promote their use.

A patient’s informed consent in this pharmaceutical fog of war…not possible.

Research put the global antidepressants market size at $11.67B in 2019 – before the mental health crisis fallout from the lockdown pandemic response. 27.4% of that market share is from SSRI drugs while another 22.6% comes from serotonin and norepinephrine reuptake inhibitors (SNRIs).  

One lesson here is when it comes to public health or mental health interventions, the public, to their detriment, will be the last to know of any true harms related to them. 

Perhaps the biggest lesson from the findings and public release of this recent systematic umbrella review debunking the serotonin hypothesis serves to show how so many have failed to understand the chokehold pharmaceutical money and influence has on the  media, government regulators, medicine, research and journals. 

For example, in 2000 Dr. David Healy was on his way to a faculty and clinical position at the University of Toronto’s Centre for Addiction and Mental Health (CAMH) when he gave a lecture “criticized pharmaceutical companies for avoiding experiments that could demonstrate problems with their drugs, and for not publishing unfavorable results. He said the data show that Prozac, and other popular antidepressants in the same chemical family, may have been responsible for one suicide for every day they have been on the market.” wrote Science Reporter in 2001.

A week later, his position offer was rescinded by the University’s Centre.

Eli Lilly was “lead” donor according to the CAMH website at the time, contributing more than $1-million to the centre’s $10-million capital-fundraising campaign.

Back then, destroying careers and pulling funding from professionals for giving well-deserved bad press to their product lines was still something the public thought was a conspiracy theory.

A slow drip of truth was allowed to reach the public over the last decade yet its effects were slow to change both the prevailing consciousness around the serotonin theory myth still influential – until now.

Mild to severe depression might be better treated with alternatives to antidepressant drugs, which do not help patients much more than an inactive placebo, researchers said TuesdayReuters 2010

Is depression caused by a chemical imbalance? There’s actually little evidence supporting this widespread belief, which was heavily promoted by the drug companies.The Week 2015

“…depression isn’t caused by a chemical imbalance, we don’t know how Prozac works, and we don’t even know for sure if it’s an effective treatment for the majority of people with depression.” – 2017

**WARNING: Coming off your medication can cause antidepressant withdrawal – and could set you up for a relapse of depression. Harvard Health writes about the dangers and symptoms of antidepressant withdrawal HERE. writes, “In a Harvard Medical School study, nearly 400 patients (two-thirds of them women) were followed for more than a year after they stopped taking antidepressants prescribed for mood and anxiety disorders. Participants who discontinued rapidly (over one to seven days) were more likely to relapse within a few months than those who reduced the dose gradually over two or more weeks.

Jefferey Jaxen

Jefferey Jaxen is a health journalist and featured in his weekly segment, ’The Jaxen Report’, on The HighWire. As an investigative journalist, researcher, and compelling writer, Jefferey serves as Lead editor of The HighWire News and Opinion Team.