Revising the History of the Serotonin Theory of Depression?


Last week, we blogged about recent coverage of the serotonin theory by NPR, which discussed the falsified status of the serotonin theory. We are happy to see that good information is now reaching the general public. However, there was a related (and perhaps even more important) issue discussed in the interview that we address below:

The scientists on NPR discuss the fact that we now know that depression is much more complex than a simple serotonin imbalance. One guest describes the serotonin story as “late 20th century thinking.” Listening to the show, you get the impression that the serotonin theory was a viable contender just a few years ago; as of 1999, for instance, a psychiatrist telling her patients that they suffered from a serotonin imbalance would have simply reflected the current psychiatric thinking; and only recently have we learned that it’s much more complicated than this…

But what if this isn’t true? What if research has indicated for decades that the serotonin theory is false, yet psychiatrists told their patients the serotonin story anyway? What would this mean?

Here are a collection of selected material from books and articles covering the evolution of the serotonin theory. Pay attention to the year:

“By 1970…[George] Ashcroft had concluded that, whatever was wrong in depression, it was not lowered serotonin.” [D. Healy, Let Them Eat Prozac]

“…the biogenic amine theory [serotonin, norepinepehrine, dopamine] now more closely resembles a venerable flag than a tool we can work with…” [Bernard Carroll, 1982, cited in Before Prozac by E. Shorter].

“The simplistic idea of ‘the 5-HT [serotonin]’ neurone does not bear any relation to reality.” John Evenden, Astra pharmaceutical company research scientist, 1990 [See Before Prozac by E. Shorter].

1991: The antidepressant drug tianeptine lowers serotonin but is found to be an effective antidepressant [See Chamba et al., 1991]

Psychiatric historian David Healy argues that the serotonin story is a marketing ploy, 1997 [See D. Healy, The Antidepressant Era]

“Although it is often stated with great confidence that depressed people have a serotonin or norepinephrine deficiency, the evidence actually contradicts these claims.” [Neuroscientist Elliot Valenstein, 1998, in Blaming the Brain]

“In truth, the  “chemical imbalance” notion was always a kind of urban legend- never a theory seriously propounded by well-informed psychiatrists.” Ronald Pies, M.D., Editor of Psychiatric Times, in 2011

By the late 1990s and early 2000s, the scientific data on the serotonin theory was not only available to psychiatrists, but there were a series of popular-press books pointing out the problems with the theory, largely driven by experimental data from studies performed from the 1970s to 1990s. It seems reasonable to assume that practicing psychiatrists were just as informed about serotonin as members of the general public who read a book like Blaming the Brain or The Undiscovered Mind. Our current discussions take place 14 years after the publication of Blaming the Brain, and at least 20 years after scientific data showed clear problems with the serotonin theory.

By 2006, Wayne Goodman, M.D., the chair of the FDA Psychopharmacological Advisory committee, had publicly conceded that the serotonin theory was but a “useful metaphor” – and one he never used in his own interactions with patients.

Yet, here in early 2012, the fact that the serotonin theory has been falsified is newsworthy and, in our experience, often surprises people.

What does this say about the state of psychiatric science and practice?

Is this simply the slow march of scientific progress, or is something else going on here?


Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.


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  1. I am very sure that serotonin is not the only cause of depression, it is just an effect. Scientists need too look more what levels are changing in the body also beside serotonin, at the moment when symptoms of depression appears.

    Also, about the SSRIs is evidently that it is all about the money. The truth will be hidden for money.
    And this is not the single time that pharmaceutic industry hides big discoveries in health domain.

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  2. Something else has definitely been going on. Psychiatrists have been intentionally dishonest with the public for all of these years because doing so has greatly benefited them. They are paid much greater because of this lie. Also, families and patients demand such an explanation when they want excuses. Parents who drug their children and adults who drug themselves demand such an explanation, even if it’s not true. I fact, both of those reasons were covered in Elliot Valensteins book. Psychiatry in bed with Big Pharma, and the patients who’d prefer to think of them and their families problems as being biological.

    These types of people will not let go of the chemical imbalance theory – even if they know it’s wrong – until it is replaced by something that serves the same purpose.

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  3. I think it is true that research in general takes about 20 years to get into the mainstream in any useful or mass-understood way. Add to that some very powerful economic interests (and their lackeys who say ‘it’s an illness like any other’) advertizing this view on the airwaves for decades and you’re likely to see what we are seeing.

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  4. Prozac (fluoxetine) has been shown to cause NEUROGENESIS in various animals, and – most exciting for me, as the mother of a kid with Down syndrome- in mice models of Down Syndrome.

    Restores cognitive ability as well. Some parents are using Fluoxetine with (mostly older) kids/teens with Down Syndrome. See the Changing Minds Foundation protocol for more info.

    Google simply Fluoxetine neurogenesis to find many studies and articles about it. This is the mechanism, not Serotonin, by which Prozac (and other SSRI’s perhaps) work, if they work. The brain is flooded with Serotonin hours after taking the first pill, yet everyone knows that Prozac’s positive effects only take place after 2 or more weeks of continuous usage.

    It’s from the neurogenesis, somehow. Exercise also shows positive benefits for the depressed. Because Exercise also creates new brain cells (by BDNF- Brain Derived Neurotropic Factor)

    look it all up! Exciting stuff.

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    • @ Liora, Thank you for sharing this information. I was surprised to speak with a woman whose son suffers from symptoms categorized as autism and is low functioning. At the age of 2 he was put on Prozac. She said it was the first time in his life that he became alert and responsive.

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  5. “In truth, the ”chemical imbalance” notion was always a kind of urban legend- never a theory seriously propounded by well-informed psychiatrists.” Ronald Pies, M.D., Editor of Psychiatric Times, in 2011

    As a layperson who is concerned with mental health advocates advancing best-practice psychiatry and patient empowerment, this is a statement that I find very confusing.

    I repect and admire the work of Dr. Peter Breggin.

    In this video Dr. Breggin states that psychiatric medications are the cause of a biochemical imbalance and “the only known cause of a biochemical imbalance in the brains of people who are depressed or anxious are the ones caused by the drugs”

    If a psychiatric medication is a substance that can induce a biochemical imbalance manifesting as psychological symptoms such as depression, psychosis, or mania, then it seems logical that there are many other substances that can also cause a chemical imbalance.

    The DSM lists many substances that can induce mood disorders/psychosis.

    What is the difference between psychological symptoms induced by psych meds in one individual and identical symptoms in another individual induced by a different substances?

    Shouldn’t all of these conditions be considered a “chemical imbalance”?

    292.84 Amphetamine-Induced Mood Disorder

    292.84 Cocaine-Induced Mood Disorder

    292.84 Hallucinogen-Induced Mood Disorder

    292.84 Inhalant-Induced Mood Disorder

    292.84 Opioid-Induced Mood Disorder

    291.89 Alcohol-Induced Mood Disorder

    292.12 Amphetamine-Induced Psychotic Disorder, With Hallucinations

    292.12 Cannabis-Induced Psychotic Disorder, With Hallucinations

    292.12 Cocaine-Induced Psychotic Disorder, With Hallucinations

    292.12 Hallucinogen-Induced Psychotic Disorder, With Hallucinations

    292.12 Inhalant-Induced Psychotic Disorder, With Hallucinations

    292.12 Opioid-Induced Psychotic Disorder, With Hallucinations

    Should we also consider factors such as Vitamin D deficiency?
    Would that be a “chemical imbalance”?

    Int J Adolesc Med Health. 2011;23(3):157-65.

    Vitamin D: a potential role in reducing suicide risk?

    Tariq MM, Streeten EA, Smith HA, Sleemi A, Khabazghazvini B, Vaswani D, Postolache TT.


    Mood and Anxiety Program, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21201, USA.


    Suicide attempts are known to peak in the spring, overlapping with the time of year when 25-hydroxyvitamin D [25(OH)D] levels are at their nadir in the northern hemisphere because of negligible skin production of vitamin D owing to low levels of ultraviolet B radiation. Low levels of 25(OH)D, the vitamin D metabolite used to diagnose vitamin D deficiency, have been associated with certain pro-suicidal factors such as exacerbation of depression, anxiety, psychosis, and certain medical conditions. Therefore, we hypothesize that vitamin D deficiency could also be associated with increased risk of completed suicides. Here, we briefly review the literature on vitamin D, its deficiency, and its reported association with certain risk factors for suicide

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  6. All the treatments that we have in psychiatry to date (with the exception of deep brain stimulation) were discovered by serendipity. It was later discovered that these drugs alter levels of monoamines (serotonin, dopamine, norepinephrine) and working backwards scientists began to investigate if individuals diagnosed with mental disorders manifest abnormalities in these neurotransmitters. While some studies have found support for the ‘monoamine theory’ other studies have not. Researchers for a long time have been trying to understand the causes of mood disorder at the biological, genetic, and psychosocial level, however the causes remain unknown. What we do know is that mood disorders are heterogeneous disorders with no one encompassing explanation. An interesting relatively new theory is the ‘cytokine theory of depression’. ‘The last two decades of research have expanded our understanding of mood disorders to include the immune system. Experiments with animals have shown that injection of proteins called pro-inflammatory cytokines (molecules synthesized and released by immune cells) induces a syndrome called ‘sickness behaviour’. This syndrome resembles depressive symptoms and behaviours in humans and includes loss of appetite, sleep disturbance, cognitive impairment, and reduced self-care behaviour. Moreover, pro-inflammatory activation in both healthy and medically ill individuals is associated with disturbances in mood, cognition, and somatic function. A wealth of evidence documents that blood levels of pro-inflammatory cytokines are abnormal in individuals with a mood disorders. Scientists are now testing treatments that reduce inflammation in individuals diagnosed with mood disorders.’ (Soczynska et al. 2011). While most of these treatments are unlikely to be available in the immediate near future, exercise, omega-3 and antioxidants also reduce inflammation and are likewise under investigation around the world to see if they offer benefits to individuals diagnosed with mood disorders. We have a long way to go but the research community is hard at work trying to unravel the mysteries behind these disorders.

    Soczynska JK and McIntyre RS (2011). Is Bipolar Disorder an Inflammatory Problem? Moods Magazine Fall issue: pg 49-50.

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  7. In a study called “Towards a possible aetiology for depression?” researchers indicated in depressions with hyperpeptiduria had high serotonin and antidepressants decreased serotonin levels. Thus, casting doubt on most double-blind trials in depression.

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  8. I think it is all too clear that biological psychiatry has been nothing but a huge fraud based on deliberate lies in colusion with BIG PHARMA. When their status was threatened by the decline of Freudian analysis, they deliberately set out to achieve equal medical status regardless of what nefarious methods they had to use. Thus, the invention of the junk science DSM III led by Robert Spitzer with a tendency to see people as rock specimens to be categorized than live human beings with normal ups and downs. Their bogus, subjective stigmas made them a perfect opportunity for BIG PHARMA with its lethal poisons passed off as medicine. Bear in mind the labels used here are forced on suffering people ignorant enought to visit a mental death expert/psychiatrist. People who come with life crises, abuse related trauma such as domestic violence, school, work and other bullying/mobbing are DELIBERATELY INVALIDATED, gaslighted and stigmatized as psychotic, delusional, ADHD, bipolar and/or the latest fraud fad stigma to push the best selling drugs still on patent, which are now the deadly antipsychotics. This despicable abuse, betrayal and retraumatization of vulnerable trauma women and child victims to collude with their fellow abusers in power is just plain EVIL! I know this from experience with loved ones with many, many different psychiatrists and whistleblower psychiatrists like Dr. Judith Herman, Dr. Frank Ochberg, Dr. Carole Warshaw and many others. They must learn these dirty tricks at school!

    I am frustrated by the seeming assumption here that just because a person gets a bogus psych label, they must be mentally ill, psychotic or other label related symptoms that have nothing to do with the so called patient now made victim again. Psychiatrists will not consider social or environmental stressors because this upsets their bogus blaming the victim con job for their own greed, profit, status and power while being handsomely rewarded by the power elite to maintain an unjust social, economic and general status quo.

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  9. I would not go as far as to say that all of psychiatry has all been a big fraud! The history of psychiatry is definitely not pretty but just like all of science and many other fields of medicine it is constantly evolving. It is one of the newest fields in medicine and compared to other organs we know very little about the brain. If you look up the history of any of the fields of medicine it will have skeletons in its closet. Having said that there are a lot of bad doctors out there that are not staying current beyond the bare minimum they need to renew their license or are only reading what they want to hear or like many people unfortunately are resistant to change. You need to shop around until you find someone who you can work with you and who is knowledgeable and current. Therapy should be a team effort. Also, I am yet to meet a psychiatrist that does not believe or invalidates stressors, trauma or other things that may have happened in someone’s life as relevant or contributory to mental issues but I guess they exist based on what people are saying on this board. Also, just because something has a psychological cause does not mean it cannot affect your body and the brain and does not mean it’s irreversible. Your entire body communicates with the brain and cannot function without it. Hunger, thirst, fear, sexual desire are all controlled by the brain. On the issue of big pharma sadly to say they are a necessary evil! When you go to the hospital and are treated with medicines that ultimately may save your life where do you think that medicine comes from and who do you think developed it or tested it and brought it to market? Having said that they have done themselves a lot of disservice by doing ridiculous and unethical things to make money. Government and academic institutions have regulated a lot of these things now so things have improved but they are still a for profit industry. Interestingly enough psychiatric medications are not necessarily their best seller anymore as most of the meds have gone generic. You think psychiatry is bad look into how much new drugs for rheumatology cost: they cost in the range of $12,000-30,000 per year! At the same time it is really expensive to bring a new drug to market that is millions and millions of dollars and often take 10 years to bring to market. A patent lasts usually 15 years so that leaves them 5 years to make their money back and try to make a profit. Keep in mind that they also test many drugs that never make it to market because they prove ineffective or not safe for people, hence millions of dollars lost. It is almost next to impossible for an independent researcher at a university to bring a drug to the market even if they discover it. You have to look at both sides of the coin. I was depressed for a long time but I did get better. It was not an easy road and I had to do a lot of my own research and go from doctor to doctor until I found what worked for me.

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    • Sorry, I’ve done tons of research on the mental death profession and based on a vast number of experts and my experience thorugh loved ones, there is no doubt in my mind that biological psychiatry is 100% fraud. You and others are right in pointing out that the rest of medicine has followed suit by selling out to BIG PHARMA, but at least it deals with real diseases and doesn’t use devious, evil lies to pass laws to force its treatments on anyone they target. This is just about social control with psychiatry the usual SS thugs of an increasing totalitarian police state.

      PLEASSSSSSSSE! Given my tons of research the last thing I would ever do is sick (sic) the mental death profession on anyone including myself! You may want to research useless but toxic psych drugs more before extolling their virtures and think they are helping. Dr. Peter Breggin’s books and web sites are very helpful.

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  10. Nothing in regards to drug company/reseach under written by them. We see similar outrage in the treatment of endometriosis, yet is it much worse in terms of impact on life. The medications for endometriosis are based on theories developed inthe late 1800’s and early 1900’s none of which are true. Yet, turning this around is almost impossible due to teh flooding of the literature of drug company sponsored research. None of which when applied to patients, despite its considerable expense, works. It is a very large con.

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  11. very interesting, article. the quotes are really quite alarming. one thing I do know about tianeptine, or Stablon, is that it is classified as a Selective Serotonin Reuptake Enhancer, it’s my understanding that the effect produced on serotonin is to lower circulating 5-HT. As you stated, it does actually produce a profound, and immediate (1-2 days) effect on alleviating depressive symptoms in what used to be a paradoxical effect, but now…. im not sure what it would be….just an effect i suppose.
    it’s interesting to note that this drug is only used in Europe and is not approved by the FDA, and has not been since it has been on the market…it doesn’t seem like it will be either. don’t get me wrong, it is not the holy grail, but from what i have read about it, it certainly seems to hold more promise than any SSRI we have on the market, and holds little to no side effects. just a side note. other wise great article. thanks!

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  12. The debunking of the chemical imbalance theory, as referred to in this article, and the increasing debate around whether antidepressants are in fact nothing more than active placebos is an emotive issue. Sadly however, most people will simply read these articles or watch such reports on television and think “hmm, that’s interesting” and get on with eating their dinner.

    However, most people’s reactions are based on considering this evidence in outpatient environments.

    Consider the impact of these revelations in an inpatient setting: where people have been deprived of their liberty; where 90% of the treatment focus lies entirely on medication; where physicians are *insistent* that the patient must agree with the chemical imbalance theory. Any patient who doesn’t is simply “diagnosed” with ansognosia and therefore likely to be incarcerated until they *get it*.

    If the Doctors in inpatient hospitals are allowed to flat out lie to patients; can treat them involuntarily with medication that offers no clinical benefit over placebo, on the basis of incorrect scientific evidence. Then it begs the question – what then, is the legal/moral justification for involuntary hospitalization?

    Given that the psychiatric profession is afforded the most extraordinary powers over other people’s liberty – do they (and society) not owe patients the truth, and treatment that actually works?

    If such lies were being perpetrated against any other group of people, such as oncologists lying to cancer patients, there would be a civil liberties uproar. But curiously, I see no such uproar in relation to those suffering from mental illness. It seems society, our government and civil rights organizations simply don’t care that we have locked people up, taken away their rights, treated people against their will on the basis of the very arguments that are being shown incorrect.

    Why does no one care about that?

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  13. There are no objective criteria for the diagnosis of “mental illness”. There is no blood test, no form of physical examination which can determine whether someone is “mentally ill” or not.

    A person who believes his mind is being invaded by alien thought beams may be safely said to have disordered thinking. However, there is no way to determine why. And therefore no way to determine whether any form of treatment works at all. People treated with anti psychotics will often claim they feel better, only to report, when the drugs are discontinued, that nothing changed apart from the ability to accurately state how they were thinking or feeling.

    Psychiatry is prone to fad diagnoses, which often become rampant after a new pill hits the market which claims to be a remedy for it. No other branch of medicine does this.

    A doctor who prescribed antidepressants to a patient who was “troubled” by a raging infection would not keep his or her license for long. Yet many with physical illnesses (notably autoimmune disorders) are referred to psychiatrists, labeled as “depressed” or similar, and pumped full of medications which as a rule leave everyone but the patient feeling better.

    If indeed there is a physical basis for “mental illness”, science may well discover it, and the discovery will be a great advance in medicine. Claims of “advances in treatment” based on nothing but statistics or consensus decision-making mock the very idea of scientific research and furthermore stifle it, to the detriment of those who genuinely suffer from mental or emotional issues.

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  14. I turned to psychiatry back in the early 1980’s not for a mood or thought problem but because of binge eating. I was desperate to get the problem to end. The only reason I became depressed at that time was because no one took my pleas seriously.

    The APA has done us no favor with its inclusion of binge eating disorder in the DSM-5 because it fails to distinguish between eating binges that are so extreme as to cause physical harm, and those eating binges where the problem isn’t the quantity, but the guilty feeling afterward.

    For myself, it was a disabling condition. I believe the cause was nutritional, and hereditary to the point that there were most likely blood sugar irregularities passed on from my mom’s side of the family. The only way to stop this extremely strong inner urge that causes a person to do something completely illogical is to alter the body chemically. Psych meds are one way, but these drugs are unsafe.

    However, that said, I found very few of these psych meds actually stopped binge eating. I’m guessing during my life I’ve taken 40 or so different psych meds at least. Many cause binge eating for me, or make it far worse, including most of the antidepressants and antipsychotics.

    If a person needs to alter their body chemically to cause change in behavior, there sure are safer and more effective ways to produce that change besides dangerous psych meds. The problem doesn’t seem to be primarily serotonin, so why are these chemicals touted so much? As was mentioned, exercise, nutritional supplements such as Omega-3’s, change in diet, and many of the non-western methods, such as acupuncture, for certain need to be explored more. I fear that inclusion of binge eating disorder in the DSM-5 may get Big Pharma on the bandwagon, meanwhile research to find safer cures won’t even be funded.

    Julie Greene

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