So Long, and Thanks for All the Serotonin

David Healy, MD
11
1006

Editorial Note:

“So Long, and Thanks for All the Serotonin,”
(the original title of this article), appears as
an editorial in the British Medical Journal
as “Serotonin and Depression

The serotonin reuptake inhibiting (SSRI) group of drugs came on stream in the late 1980s, nearly two decades after first being mooted. The delay centred on finding an indication. They did not have hoped-for lucrative antihypertensive or antiobesity profiles. A 1960s idea that serotonin concentrations might be lowered in depression1 had been rejected,2 and in clinical trials the SSRIs lost out to the older tricyclic antidepressants as a treatment for severe depression (melancholia).3-5

When concerns emerged about tranquilliser dependence in the early 1980s, an attempt was made to supplant benzodiazepines with a serotonergic drug, buspirone, marketed as a non-dependence producing anxiolytic. This flopped.6 The lessons seemed to be that patients expected tranquillisers to have an immediate effect and doctors expected them to produce dependence. It was not possible to detoxify the tranquilliser brand.

Instead, drug companies marketed SSRIs for depression, even though they were weaker than older tricyclic antidepressants, and sold the idea that depression was the deeper illness behind the superficial manifestations of anxiety. The approach was an astonishing success, central to which was the notion that SSRIs restored serotonin levels to normal, a notion that later transmuted into the idea that they remedied a chemical imbalance. The tricyclics did not have a comparable narrative.

Serotonin Myth

In the 1990s, no academic could sell a message about lowered serotonin. There was no correlation between serotonin reuptake inhibiting potency and antidepressant efficacy. No one knew if SSRIs raised or lowered serotonin levels; they still don’t know. There was no evidence that treatment corrected anything.7

The role of persuading people to restore their serotonin levels to “normal” fell to the newly obligatory patient representatives and patient groups. The lowered serotonin story took root in the public domain rather than in psychopharmacology. This public serotonin was like Freud’s notion of libido—vague, amorphous, and incapable of exploration—a piece of biobabble.8 If researchers used this language it was in the form of a symbol referring to some physiological abnormality that most still presume will be found to underpin melancholia—although not necessarily primary care “depression.”

The myth co-opted the complementary health market. Materials from this source routinely encourage people to eat foods or engage in activities that will enhance their serotonin levels and in so doing they confirm the validity of using an antidepressant.9 The myth co-opts psychologists and others, who for instance attempt to explain the evolutionary importance of depression in terms of the function of the serotonin system.10 Journals and publishers take books and articles expounding such theories because of a misconception that lowered serotonin levels in depression are an established fact, and in so doing they sell antidepressants.

Above all the myth co-opted doctors and patients. For doctors it provided an easy short hand for communication with patients. For patients, the idea of correcting an abnormality has a moral force that can be expected to overcome the scruples some might have had about taking a tranquilliser, especially when packaged in the appealing form that distress is not a weakness.

Costly Distraction

Meanwhile more effective and less costly treatments were marginalised. The success of the SSRIs pushed older tricyclic antidepressants out of the market. This is a problem because SSRIs have never been shown to work for the depressions associated with a greatly increased risk of suicide (melancholia). The nervous states that SSRIs do treat are not associated with increased risk of suicide.11 The focus on SSRIs also coincided with the abandonment of the pursuit of research into established biological disturbances linked to melancholia (raised cortisol); the SSRIs are ineffective in mood disorders with raised cortisol.12

Over two decades later, the number of antidepressant prescriptions a year is slightly more than the number of people in the Western world. Most (nine out of 10) prescriptions are for patients who faced difficulties on stopping, equating to about a tenth of the population.13,14 These patients are often advised to continue treatment because their difficulties indicate they need ongoing treatment, just as a person with diabetes needs insulin.

Meanwhile studies suggesting that ketamine, a drug acting on glutamate systems, is a more effective antidepressant for melancholia than SSRIs cast doubt on the link between serotonin and depression.15-17

Serotonin is not irrelevant. Just as with noradrenaline, dopamine, and other neurotransmitters, we can expect it to vary among individuals and expect some correlation with temperament and personality.18 There were pointers to a dimensional role for serotonin from the 1970s onwards, with research correlating lowered serotonin metabolite levels with impulsivity leading to suicidality, aggression, and alcoholism.19 As with the eclipse of cortisol, this research strand also ran into the sand; SSRIs lower serotonin metabolite levels in at least some people, and they are particularly ineffective in patient groups characterised by impulsivity (those with borderline personality traits).20

This history raises a question about the weight doctors and others put on biological and epidemiological plausibility. Does a plausible (but mythical) account of biology and treatment let everyone put aside clinical trial data that show no evidence of lives saved or restored function? Do clinical trial data marketed as evidence of effectiveness make it easier to adopt a mythical account of biology? There are no published studies on this topic.

These questions are important. In other areas of life the products we use, from computers to microwaves, improve year on year, but this is not the case for medicines, where this year’s treatments may achieve blockbuster sales despite being less effective and less safe than yesterday’s models. The emerging sciences of the brain offer enormous scope to deploy any amount of neurobabble.21 We need to understand the language we use. Until then, so long, and thanks for all the serotonin.

Competing interests: I declare I am a founder member of RxISK, which works to raise the safety profile of medicines and is on the advisory board of the Foundation for Excellence in Mental Health Care. I have acted as an expert witness in cases relating to suicide and violence and SSRIs.

* * * * *

References:

1. Ashcroft GW, Sharman DF. 5-Hydroxyindoles in Human Cerebrospinal Fluids. Nature 1960;186:1050-1.

2. Ashcroft GW. The receptor enters psychiatry. In: Healy D, ed. The Psychopharmacologists. Vol 3. Arnold, 2000:189-200.

3. Danish University Antidepressant Group. Citalopram: Clinical Effect Profile in Comparison with Clomipramine. A Controlled Multicentre Study. Psychopharmacology 1986;90:131-8.

4. Danish University Antidepressant Group. Paroxetine. A Selective Serotonin Reuptake Inhibitor Showing Better Tolerance but Weaker Antidepressant Effect than Clomipramine in a Controlled Multicenter Study. Journal of Affective Disorders 1990;18:289-99.

5. Healy D. The Antidepressant Era. Harvard University Press, 1997.

6. Lader M. Psychopharmacology: clinical and social. In: Healy D, ed. The Psychopharmacologists. Vol 1. Chapman and Hall, 1996:463-82.

7. Healy D. Let Them Eat Prozac. New York University Press, 2004.

8. Healy D. Unauthorized Freud:Doubters Confront a Legacy. British Medical Journal 1999;318:949.

9. Ross J. The Mood Cure. Penguin, 2002.

10. Andrews PW, Bharwani A, Lee KR, Fox M, Thomson JA. Is Serotonin an Upper or a Downer? The Evolution of the Serotonergic System and its Role in Depression and the Antidepressant Response. Neuroscience and Biobehavior Reviews 2015;51:164-88.

11. Boardman A, Healy D. Modeling Suicide Risk in Affective Disorders. European Psychiatry 2001;16:400-5.

12. Shorter E, Fink M. Endocrine Psychiatry. Oxford University Press, 2010.

13. Healy D, Aldred G. Antidepressant Drug Use and the Risk of Suicide. Int Rev Psychiatry 2005;17:163-72.

14. Spence R, Roberts A, Ariti C, Bardsley M. Focus on: Antidepressant Prescribing. Trends in the Prescribing of Antidepressants in Primary Care. Health Foundation, Nuffield Trust, 2014.

15. Berman RM, Capiello A, Anand A. Antidepressant effects of ketamine in depressed patients. Biological Psychiatry 2000;47:351-4.

16. Murrough JW. Ketamine as a Novel Antidepressant: From Synapse to Behavior. Clinical Pharmacology Therapeutics 2012;91:303-9.

17. Atigari OV, Healy D. Sustained antidepressant response to ketamine. British Medical Journal Case Reports 2013. doi:10.1136/bcr-2013-200370.

18. Cloninger CR. A Systematic Method for Clinical Description and Classification of Personality Variants: a Proposal. Archives of General Psychiatry 1987;44:573-88.

19. Linnoila M, Virkkunen M. Aggression, Suicidality and Serotonin. Journal Clinical Psychiatry 1992;53(suppl):46-51.

20. Montgomery DB, Roberts A, Green M, Bullock T, Baldwin D, Montgomery S. Lack of efficacy of fluoxetine in recurrent brief depression and suicide attempts. European Archives of Psychiatric Clinical Neuroscience 1994;244:211-5.

21. Delamothe T. Very Like a Fish. British Medical Journal 2011;343:d4918.

11 COMMENTS

  1. A few things. First of all, thank you for acknowledging the fraudulent history of psychiatry, including the deceptive “chemical imbalance” hypothesis. This is a surface level myth that is still very powerful, and it needs to be debunked regularly and publicly, especially by those who claim to be doctors or medical professionals.

    Second, we need a little more honesty concerning the use of the terms “effective” and “ineffective.” We also need a little more honesty about terms like “treatment,” and “medicine.” When “effective” means “creating chemical lobotomies” or “inducing a stupor of sedation,” then we know that there is something wrong with our use of the words “medicine” and “treatment.” Pay attention to what these drugs actually are, and note the actual damage that they cause to the brain.

    Third, underneath all of the psychobabble and biobabble runs a current of scientism, or in other words, a reductionist paradigm in which human beings are regarded as nothing more than complex biological machines or conglomerations of particles, atoms and molecules. Such a narrow view of history (and a simplistic view of science) confines us to a shallow post-modern paradigm, inuring us with a false security that the “emerging sciences of the brain” hold the answers to questions that have plagued philosophers for millennia.

    These surface level conundrums must be addressed, and these hackneyed hypotheses must be laid to rest. But we need vibrant thinkers who see through the shallowness of our time, and beyond the chaos of a few decades.

    Of course the author cannot possibly address all of these concerns in one article, but if anything, this is a plea for those who claim to be doctors and scientists to study a little history and a little philosophy. There should not be a medical student allowed to graduate who does not understand something of the long history of medicine, including the long history of the abuses of “medicine,” up to the post-modern period of the psychopharmaceutical industrial complex and the therapeutic state. Medical students should be required to think, to reason, and to discern truth from error. By doing so, they would certainly avoid embroiling themselves in the pseudo-scientific field of psychiatry, and many of them would probably abandon the medical profession in search of ways to truly serve and bless their fellow man.

    The really smart ones would begin to realize that what they are taught to practice is not medicine at all, but a ritualistic implementation of cultish dogmas rooted in the mistaken notions of relativistic, post Enlightenment creedalism.

    Since it is unlikely that modern medicine will wise up, perhaps our only hope is to educate the masses in order that they take responsibility for their own health rather than yielding their liberties to a priestly class of medical elite.

    “We need to understand the language we use.”

    Unfortunately there is hardly a self proclaimed doctor or medical professional alive who understands where our language really comes from. When everything has been detached from the King’s English as set in motion by the likes of Tyndale with his Bible and Shakespeare with his works, we are destined to be mired down in an oozing sludge of pseudo-scientific post-modern vocabulary that postures as “evidence-based medicine.”

    While it is important to debunk the false hypotheses surrounding the “chemical imbalance” myth, and to pick apart the pseudo-scientific dogmas of psychiatry, it is more essential to see through the larger myth of “mental illness.” Foucault, Szasz, Breggin, Whitaker and others have done a lot of the spade work already, but we need fresh, vibrant articulators of truth to step forward and seize history from the grimy clutches of psychiatric apologists.

    As Szasz clairvoyently observed so long ago: “In the animal kingdom, the rule is, eat or be eaten; in the human kingdom, define or be defined.”

  2. You mention anxiety. Anxiety can drive a person into a mental hospital but there are very good straightforward ways of dealing with it. Like gradually reducing worry periods and recognising how worries become less important as a result. But I think the old rule applies concerning tranquillizers – that anything taken as an easy option will make the problem worse in the long term. I know lots of people suffering now from terminal withdrawal syndrome as a result of SSRI s (and long term psychiatric).

  3. Thank you, as always, for speaking the truth, Dr. Healy.

    “In other areas of life the products we use, from computers to microwaves, improve year on year, but this is not the case for medicines, where this year’s treatments may achieve blockbuster sales despite being less effective and less safe than yesterday’s models.”

    Perhaps as a world we need to somehow break up the pharmaceutical cartel into many smaller companies, so we can bring about some actual competition, thus hopefully better products. Obviously, the current non-competitive nature of the pharmaceutical industry is not benefitting humanity as a whole.

  4. The assertion that they had ruled out low serotonin – as if they were somehow lofty experts – is invalidated by these people’s scientific and Medical integrity. Psychopharmacologists and the APA, NIMH, NAMI Nosologic-name-labeling-as-diagnosis- Drug-Shock-Psychosurgery as therapy” chjild poisoners for profit… have no integrity.

    Prozac the first “SRI” in the USA, as we know because of Baum Hedlund Law Firm, was known in house to cause suicide… known before 1986.

    Planned lies was their response.

    They create pro-forma “Reports” for the ersatz “Professional Peer-Review Journals.

    Because of Robert Whitaker we know the faking of the “atypicals.”

    Because of David Horrobin and <acolm Peet we know that clozapine did have a novel unexpected form of action (instead of being a Thorazine Me-too).

    Since 1973 Fraud has been all of NAMI, APA, NIMH "Psychiatry."

    THe only science they have had since 1973 is propaganda.

    ____________________

    With Donald F. Klein, M.D. at the leadership of Chemotherapy in Psychiatry and Max Fink at the helm of Electroshock Treatment – they forged the fraud.

    With the DSM-3 Fraud and Donalds professional publications they made the show where-in diagnosis would be by naming (selection, Doctors as authority selectors) and therapy would be chemotharapy with patented prescription centrally acting drugs, exclusively. (Plus Electroshock and Psychosurgery the other academic and treatment modality wings of the new Psychiatry.

    Trillions of dollars in blood money.

    ___________________________________________

    Evelyn Pringle – The Antipsychiatry Movement
    http://www.lawyersandsettlements.com/…/drug…

    PsycheTruth – The Antipsychiatry Movement
    ADHD Drugs vs. Possible Cures – Nutrition by Natalie
    ADHD Warning – Nutrition by Natalie – YouTube
    https://www.youtube.com/watch?v=GPBo2cstNMI

    Anti Psychiatry Movement ! ! "Medical" Psychiatry is Fraud with its Chemotherapies. The MOTHERS Act (included inside Obama Care ) is a "GAME" to increase PATENT DRUG Sales by Targeting OUR Women and Toddlers.

    John Breeding, PhD Psycholgist, Amy Philo and The Bitter Pill, Evelyn Pringle
    https://www.youtube.com/watch?v=tzb2gD1fWpE

    Psychiatry's Patented Drug version of Chemotherapy in Psychiatry/ Psychology became out-and-out INTENTIONAL FRAUD between 1954 and 1967. By 1970 there entire Fraud Program had been planned.

    Abram Hoffer, M.D. created the modern chemotherapy in Psychiatry. The researchers of his kind were Intentionally Suppressed by the NIMH/APA/Drug Companies in 1973 (with the publication of the 58 page Task Force #7 Report of the American Psychiatric Association.

    Likewise the creation of NAMI was intentional planned Fraud.

    And the writing of DSM3, "the DSM3 project" published in 1980.

    After already being joined by the premere Biochemist of the USA – Linus Pauling – Abram Hoffer, M.D., Ph.D. and fellow legit real doctors and biochemists were suppressed with the fraudulent 1973 peer-review TF7.

    Here Abram Hoffer states how Psychiatry was overwhelmed by the drug companies tranquiller profits between 1956 to 1958

    IFM Interview: Dr. Abram Hoffer and Dr. Jeffrey Bland
    https://www.youtube.com/watch?v=RE2rpITjlhI

    Dame Judi Dench, Peter Defazio and others discuss
    CODEX – The War on Health Freedoms, The Human Right to Health, Food, Real Information, Life

    We Become Silent – The Last Days of Health Freedom
    https://www.youtube.com/watch?v=Qjd7b4lHRl8

    The same baby and pregnant women poisoning snakes of "psychiatry" with their propaganda based fraud version of chemotherapy in Psychiatry are the same people of Quackwatch, they are the same as E. Fuller Torrey and DJ Jaffe, they are Sceptical Enquired, they are Codex, they are Merke, they are the vaccine merchants, they are the Codex Alimentarius people, they are Monsanto, they are capitalism that has left ethics and morality behind and become CRIMINAL.

    Daniel Burdick "Michael Valentine Smith" S.E.A. – Springfield Eugene Antipsychiatry April 2015

    341 East 12th Avenue
    Eugene Oregon, 97401

    ______________________________________

  5. The two questions

    Does a plausible (but mythical) account of biology and treatment let everyone put aside clinical trial data that show no evidence of lives saved or restored function?

    Yes, it has done that. The plausible serotonin deficiency theory (which no one has ever stated, advocated, or believed), is a placeholder in the public discourse. Even after hearing that was abandoned a long time, that just sounds like it was the wrong theory of a biological basis for MDD. So even though the plausible myth is gone, another one will come down the pike.

    Biological (chemical) treatment went large with Prozac’s portrait on the cover of Time. That is the day the (plausible, mythical) stigma of seeking mental health services took a big old
    Nembutal and took to its bed.

    With the two pillars, biologic theories and chemical treatments, set deep in bedrock, immune to stigma, and questioned at the moment by just a handful of public figures (plus alt media, a layer of bloggers, and layer of commenters and forum posters), why would anyone bother to examine clinical trial data? With the peristance and expanded reach of antidpressants, stimulants, APs, etc, why would a regular person believe the FDA approved them based on trials that were weak or fraudulent? No reason.

    Which reminds me. I just took a hard look at a trial of Vortioxetine the other day (Brintellix). It simply cannot have used human subjects. I have just a sliver of the people who try it able to tolerate the side effects, or getting any benefit. They rarely last more than a few weeks on it, per my extensive searches of the main drug forums, which are mainly pro drug and pro polydrug in tone, the results are not easy to accept. A confound is that lots of the threads I follwed were by polydruggers adding it to cocktails.

  6. 2. Do clinical trial data marketed as evidence of effectiveness make it easier to adopt a mythical account of biology? There are no published studies on this topic.

    I assume that the question refers to TV ads that might cite findings like:

    “Patients taking Agitraton 300kg/day were four times more likely to experience reductions in the severity of the four primary symptoms of major depressive disorder compared to patients taking Pharmatrol .5mg/day.

    Patients on Agitraton were significantly less likely to report serious adverse events (89%) than were patients taking Pharmatrol (100%).”

    Ads like that would be accepted without question by a lot of viewers who have been primed to believe the plausible/mythical theory.

    Would they cause someone who was unaware of the plausible/mythical bio explanation of depression deduce it from the trial data? Maybe.

    No, not if they believe antidepressants are happy-pills like Ecstasy and stimulants.

    and

    Yes, if they have been told that antidepressants correct a deficiency just like iron supplements do. The Party Line and maybe the original message I heard about Prozac when it was new was a version of the plausible/mythical account of depression. People were worried that Prozac was a happy pill, and thought that taking it was a cop-out. No, we were assured. All prozac does is is restore your available brains serotonin to an optimal level.

    In that case, the plausible/ mythical cause for depression is fortified by the “scientific” research.

  7. I discussed this with a concerned journalist colleague, who recommended that I and other psychiatrists who have some expertise in this area nominate ourselves upon the Science Media Centres in our respective countries so as to provide a more measured, scientifically grounded, perspective upon stories such as these.

    There is a Science Media Centre of the United States, website here http://www.sciencemediacenter.org/usa/ , which has links to the Science Media Centres of Australia, Canada, New Zealand, Japan and United Kingdom.

    If you are a psychiatrist or pharmacologist reading this list post please consider nominating yourself as an expert to the Science Media Centre in your relevant country so as to provide a more grounded, measured, scientifically focused perspective upon stories such as these.