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Lacasse, 2015 Antidepressants and the Chemical Imbalance Theory of Depression: A Reflection and Update on the Discourse

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A decade ago (2005) Lacasse and Leo published an article about the serotonin deficiency theory of depression.




This is a 2015 reflection and update on the discourse.


Florida State Universities Libraries, Faculty Publications, College of Social Work.

Lacasse J. R. and Leo J. 2015, Antidepressants and the Chemical Imbalance Theory of Depression: A Reflection and Update on the Discourse.


Refer full text here- http://diginole.lib.fsu.edu/islandora/object/fsu%3A267045


In 2005 Lacasse and Leo found that,


 "Advertisements did not accurately reflect the scientific status of the serotonin theory in the psychiatric research community. Some advertisements were more tentative or clever in their wording than others, but it seemed obvious that the drug companies were at least pushing the boundaries. We thought several of them were going over the line in plain sight of the FDA, which ostensibly regulates direct to consumer advertising. Our goal was to illustrate the clear disconnect between the existing psychiatric science and what the public was being told in these advertisements and we argued that the FDA should issue warning letters to pharmaceutical companies. Of course there were ramifications for clinicians – if it was illegal to claim this in advertisements, wasn't it also an unacceptable thing to be telling vulnerable clients? "


The Problematic Advertisements Disappear
"Newer medications were promoted as "adjusting" or "affecting" neurotransmitter levels, in contrast to "correcting a chemical imbalance"...(...) .. And drugs are now advertised as "affecting" neurotransmitters.

There is no public explanation for why this happened. To our knowledge, the FDA has never sent a warning letter to a pharmaceutical company over claims that antidepressants corrects a chemical imbalance. In our assessment, the promotion of chemical imbalances theory in advertise mince for SSRI drugs was wildly successful for the drug companies in the psychiatric profession alike. Wallace difficult to imagine that they pulled them arbitrarily, we don't know why they largely disappeared."


The authors suggest it may be due to the widespread public criticism of it and emerging transparency of information on the Internet obviously creating problems, or at least a dilemma.


The authors highlight a few examples of the recent discourse on these issues under the following headings:


I Don't Really Believe It, But I Say It to Patients Anyway

Psychiatrist Daniel Carlat is a practising psychiatrist, a clinical instructor at Tufts University ..(..)...


"I think I say that because patients want to know something. And they want to know that we as physicians have some basic understanding of what we're doing when we are prescribing medications. They certainly don't want to know that a psychiatrist essentially has no idea how these medications work."


...(..)...The consistent lack of difference between SSRI and placebo in the clinical literature is one of the most compelling arguments against the serotonin deficiency theory...(...)... one thing that has happened is that because there's been such a vacuum in our knowledge about mechanism, the drug companies have been happy to sort of fill that vacuum with their own version of knowledge...(..)... in fact scientists have known for a long time that the serotonin theory presented by the drug companies and Carlat is not true.....(...)... the simple alternative would be to tell patients the truth – that the pathophysiology of depression is unknown and that we have no idea how SSRIs work.


The Positive Aspects of Misinformed Thinking
There were many angry comments... Apparently many psychiatric patients never realised they were hearing a metaphor and not science....(...)... some such patients now understandably feel lied to by the clinicians. The claim that presenting the chemical imbalance metaphor is in the best interests of patients needs to be considered in light of the existing empirical research. This in fact is not what the literature shows.


The Role of Journalism

It Wasn't Us, It Was the Drug Companies

Ronald Pies is a psychiatrist at Tufts University....(...)... Pies doesn't believe that the chemical imbalance metaphor should be attributed to psychiatry...


" In truth the chemical imbalance notion was always a kind of urban legend – never a theory seriously propounded by well-informed psychiatrists". 


...(...)..[Yet]... Among 237 psychology students Francis, Lysaker and Robinson found that 46% had heard the chemical imbalance explanation from a physician ..... Many people reported hearing it's a 'chemical imbalance' from psychiatrists.... If Pies is correct, that is an awful lot of uninformed clinicians.


A Bumper Sticker Slogan to Educate Patients
In subsequent articles Pies moderates his tone...... he claims that it is the result of overbooked clinicians looking for quick explanations to accompany medication, perhaps to reduce self blame on the part of patients(he acknowledges this may backfire). ....(...)... academic psychiatry in general has done a highly effective job of convincing PCPs to diagnose and treat depression with antidepressants.


Academic Psychiatry As Silent Partner in the Promotion of Chemical Imbalance
...Prominent academic psychiatrists could have set the record straight on serotonin imbalance decades ago. Yet to our knowledge no one did so....(...)... is it possible that the flow of money from the pharmaceutical companies to influential academic psychiatrists… has brought with it a certain willingness to remain silent?


[Pies] sounds vaguely critical of the drug industry in his recent articles and never discloses any history of financial conflicts of interest. However Pies has received funding from....[lists many pharma companies]. Pies blames the drug companies for running misleading advertisements about chemical imbalance, belatedly admits he should have said something sooner, but fails to mention that he was paid to help them promote their products at the time the advertisements were running.


But We Never Promoted the Theory


In Table 1 and Table 2 it is apparent that there are often two different conversations occurring. One is the actual scientific discourse. The other conversation is between influential psychiatrists and the public, or between psychiatrists and primary care physicians. In this second conversation the company advertising line about SSRIs correcting chemical imbalances is repeated as fact by psychiatric authorities including the APA.


[i recommend having a read of:

Table 1- Evidence the chemical imbalanced theory of depression is not valid: selected quotations and,

Table 2-Promotion of the chemical imbalance theory of depression as valid: selected quotations].


The Chemical Imbalance Theory Is a Little White Lie
.. By 2014 Pies refers to the use of the chemical imbalance metaphor as "a little white lie"....(...)... how many patients with reservations about SSRIs have agreed to take medication after being told this "little white lie"?




... The propagation of misleading advertising is only possible in the absence of vigorous government regulation… Or outcry from professional associations. That outcry never came....(...)...


...while we are hesitant to overemphasise conflicts of interest as an explanation for what has occurred, we can't help but notice that the silence of psychiatry regarding chemical imbalance only ended when the profits had been extracted from the SSRI marketplace.


The new narrative will apparently be that psychiatrists recently discovered that the chemical imbalance theory was incorrect. Psychometric researchers are changing their mind based on the data, so the story goes and adjusts took a while to let the public know. We believe this is empirically incorrect. The idea that the withdrawal of the chemical imbalance theory was caused by recent data should be rejected.


As the theory has been withdrawn and a dialogue has taken place, many mental health clients have reacted negatively to the news that there was never any reason to believe that depression was caused by a serotonin imbalance.


Many mental health clients find it unacceptable, and perhaps a violation of ethical informed consent, for clinicians to give patients metaphorical explanations for their mental health problems and promote them as scientific truth.


Patients who start an SSRI because they have been told it will correct the chemical imbalance, that it is like thyroid medication for hyperthyroidism are likely to eventually conclude that they have simply not been told the truth.


Previously we argued that misleading consumer advertisements for SSRIs should  end (2005).


A decade later the serotonin theory of depression is acknowledged to be dead and most SSRI advertising campaigns are now part of history....(...) we encourage our colleagues in organised psychiatry to work towards this end by improving medical education and ongoing training, by endorsing shared decision-making, and by ensuring that informed consent is based on the scientific literature.

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Interesting article. Good find.

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Table 1. Evidence the Chemical Imbalance Theory of Depression Is Not Valid: Selected Quotations


“By 1970… [biochemist and Nobel Prize winner Julius] Axelrod had concluded that whatever was wrong in depression, it was not lowered serotonin.” Healy, 2004


“I spent the first several years of my career doing full-time research on brain serotonin metabolism, but I never saw any convincing research that any psychiatric disorder, including depression, results from a deficiency of brain serotonin” (Psychiatrist David Burns, who conducted award-winning serotonin research in the 1970s). Lacasse and Gomory 2003.


Tianeptine is an interesting compound with antidepressant activities thought to be related to increased rather than decreased SHT [serotonin] uptake” [meaning, in 1989 and was known to be an antidepressant that depletes, not increases, serotonin]. Ives and Heym, 1989“The simplistic idea of the 5-HT [serotonin] neurone does not bear any relation to reality” (John Evans and Astra pharmaceutical company research scientist, 1990). Shorter, 2009.


“In the 1990s… No one knew if SSRIs raised or lowered serotonin levels; they still don’t know… There was no evidence that treatment corrected anything.” Healy 2015.


“… Patients have been diagnosed with ‘chemical imbalances’ despite the fact that no test exists to support such a claim, and there is no real conception of what a correct chemical imbalance would look like… Yes conclusions such as ‘depression is a biochemical imbalance’ are created out of nothing more than semantics and the wishful thinking of scientists/psychiatrists and a public that will believe anything now that has the stamp of approval of medical science” (Psychiatrist David Keiser of Northwestern University Hospital, 1996). Keiser, 1996; Lynch, 2015. p31-32.


“Although it is often stated with great confidence that depressed people have a serotonin or norepnephrine deficiency, the evidence actually contradicts these claims.” (neuroscientist Elliot Valenstein). Valenstein, 1998.


“The Monamine hypothesis… Holds that monamines… such as… [serotonin]… are deficient in depression and that the action of antidepressants depends on increasing the synaptic availability of these monamines… However, inferring neurotransmitter pathophysiology from… SSRIs… Is similar to concluding that because aspirin causes gastrointestinal bleeding, headaches are caused  caused by too much blood… Additional experience has not confirmed the monamine depletion hypothesis.” American Psychiatric Association textbook of psychiatry, 1999). Dubvosky and Buzan, 1999.


“A serotonin deficiency for depression has not been found” (Psychiatrist Joseph Glenmullen, clinical instructor of psychiatry at Harvard Medical School)). Glenmullen, 2000.


“... I wrote that Prozac was no more, and perhaps less, effective in treating major depression than prior medications… I argued the theories of brain functioning that led to the development of Prozac must be wrong or incomplete.” (Brown University psychiatrist Peter Kramer author of Listening to Prozac). Kramer, 2002.


“[We must] abandon the simplistic hypothesis of there being either an abnormally high or abnormally low function of a given neurotransmitter.” (Avrid Carlson, Noble Prize winner for his work on the neurotransmitter dopamine, 2002). CINP Meeting with the Nobles 2003; Shorter 2009.


“ Indeed, no abnormality of serotonin n depressed and has ever been demonstrated.” Healy 2004.

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What galls me the most is the conflict of interest that seems so prevalent in psychiatry. It doesn't appear to be as prevalent in other parts of medicine. It seems like the anti-kickback laws are not enforced in psychiatry like they are in cardiology, etc. I work in the medical field and we have to do compliance training annually concerning this very thing. What gives? I don't get it...

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Table 2. Promotion of the Chemical Imbalance Theory of Depression As Valid: Selected Quotations


"Celexa helps to restore the brain's chemical balance by  increasing the supply of a chemical messenger in the brain called serotonin". Source: Celexa website, 2005.


"Antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain." Source: Let's Talk Facts about Depression, a patient information leaflet distributed by APA. 2005


"Antidepressants… have no effect on normal mood. They restore brain chemistry to normal." Source: Father Stotland, president of the American psychiatric Association, 2007 – 2008. Cited in Stotland, 2001.


"[Antidepressants work] only if there was a chemical imbalance in the brain that needed fixing", Source: Donald Klein, psychiatrist and psychopharmacologist cited in Talan, 1997.


"While the patient may require a somatic therapy to correct the underlying chemical imbalance: he may also need psychotherapy…" Source Nancy Andreason,  psychiatrist and author of The Broken Brain. Citation Andreason, 1985.



"... Some depressed patients who have abnormally low levels of serotonin respond to SSRIs…" Psychiatrist Richard Friedman in the New York Times, 2007.


"There is truly a real deficiency of serotonin in depressed patients." Source: Psychiatrist Charles Nemeroff, 2007.


"The physician should stress that depression is a highly treatable medical illness caused by a chemical imbalance." Source: MacArthur Foundation Depression Education Program for Primary Care Physicians. Citation Cole, Raju, Barrett, Gerrity and Dietrich 2000.


"Patients with neurotransmitter dysregulation may have an imbalance of serotonin in norepinephrine… duloxetine [Cymbalta] may aid in correcting the imbalance of serotonin and norepinephrine neurotransmission in the brain." Source: Makur Trivedi, Psychiatrist at University of Texas Southwest medical School, in the primary-care companion in the Journal of clinical psychiatry. Citation: Trivedi 2004.


"Restoring serotonin's imbalances not only helps brighten mood and restore normal sleeping and eating patterns, but it also seems to promote a sense of well-being." Source: Michael Thase, Psychiatrist and psychopharmacology researcher at the University of Pennsylvania, and science writer Susan Lang. Citation: Thase and Lang, 2004.


"We now know that mental illnesses – such as depression or schizophrenia – are not moral weaknesses or imagined but real diseases caused by abnormalities of brain structure and imbalance in chemicals of the brain… Medications and other treatments can correct these imbalances. Talk therapy can directly improve brain functioning." Source: Richard Harding, President of the American Psychiatric Association, 2000 – 2001.


"At some time in the course of their illness, most patients and families need some explanations of what has happened and why. Sometimes the explanation is as simplistic as 'a chemical imbalance'…" Source: Robert Friedman, Psychiatrist at the University of Colorado. Citation: Friedman, 2003 as cited by Hickey, 2014.

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I guarantee you that if you scratch the sources of Table 2 hard enough you'll find a mind boggling array of conflicts of interest.


I wonder how Richard Friedman is measuring these 'abnormally' low levels of serotonin? [or any level for that matter!]


What is incredibly tragic is that people like Hickey  in 2014 are citing this nonsense.


But Hickey is not alone ....in 2015 Lieberman (a former president of the APA (2014) and current director of a NY Psychiatric Institute) was cheer-leading this balony as well with an 'insulin for diabetics' inference...when criticizing Whitaker on a radio interview.


Lieberman: “Is [Whitaker] wrong? What he says is preposterous. He’s a menace to society because he’s basically fomenting misinformation and misunderstanding about mental illness and the nature of treatment. What he just said in that clip you ran about, if you’re taking an antidepressant and you go off it and you get sick again… the same thing could be said about insulin for diabetes and asthma medication… Whitaker, he ostensibly considers himself to have been a journalist, God help the publication that employed him, but he has an ideological grudge against psychiatry for whatever reason and there’s no, what he calls research is simply his opinion and his construction of information."
Enright: "What about his contention that the unmedicated patients did better than the medicated patients?"
Lieberman: "I’d say that’s absolutely wrong. If you do a controlled study with various illnesses, whether it’s schizophrenia, depression, bipolar disorder, obsessive compulsive disorder, and you do a randomized study, assign one group to receive whatever the state of the art is in psychiatry including medication and you assign the other to some innocuous, non-medical type of supportive therapy or whatever, and you follow the people for a period of time the outcomes will be extraordinarily superior in the treated group. The magnitude of the difference we can sort of quibble about, but there’s no doubt about it."
Jeffrey A. Lieberman, MD, is the Lawrence C. Kolb Professor and Chairman of Psychiatry at the Columbia University College of Physicians and Surgeons and Director of the New York State Psychiatric Institute. Formerly the President of the American Psychiatric Association, in 2000 was elected to the National Academy of Sciences Institute of Medicine. He lives with his wife and two sons in New York City.



In 2014 Jeffrey Lieberman, APA President at the annual meeting had this to say  (speech excerpt)...


"We have been waiting, many of us our whole lives, for the chance to change the way the world thinks of psychiatry and the way we think of ourselves as psychiatrists. Let's use the momentum we have to plunge ahead into the next year with our confidence brimming, our energy renewed, and our sights set high… this is our opportunity to change the practice and perception of psychiatry for the better and as never before. Last year, standing on the stage in San Francisco, I told you that "our time has come." Today, I say to you that our future is now! "


Cant help but be reminded of a few other famous speeches...


 “Our enemies are innovative and resourceful, and so are we. They never stop thinking about new ways to harm our country and our people, and neither do we.”                    President George W. Bush, August 5th, 2004.


"Intelligence is our first line of defence." President George W.Bush


[perhaps Jeffrey is using denial as his first line of defence... ]


"Sometimes people don't want to hear the truth because they don't want their illusions destroyed." Frederick Nietzsche


"Everything was perfectly normal and healthy here in Denial land."  Jim Butcher


Jeffery you may well be suffering I.E.D.

Any of those in the DSM?


'Impervious to Evidence Disorder' you do not listen to disconforming evidence and you respond to criticism like an I.E.D. !

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NZ11 - who is "Hickey"?

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He is an author(?) in table 2 referencing mythical beliefs -see last line


oops maybe Hickey is one of the good guys pointing out the bad guys.....just found this article looks like a long read...im all read out at the moment but feel free to peruse this.



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