A while back I posted about how the “chemical imbalance theory” was a meme that originated in pharmaceutical advertising and all of the evidence to support that observation. This post is about whether that was really a trope and also why psychiatrists should not do too deep of a dive into the neurobiology of medications as a reaction. My concern about the deep dive came from something I saw on LinkedIn, that made the mistake of taking chemical imbalance quite literally rather than the rhetoric commonly used by the detractors of psychiatry. The suggested strategy was outlining the known neurobiology of antidepressants – a strategy I do not favor.
First things first.
The difference between a meme and a trope has always seemed poorly
delineated. Richard Dawkins is credited
with defining a meme as a unit of cultural transmission for
evolutionary purposes. Common modern
usage is that it is an image, piece of text, or video that spreads rapidly on
the internet and is adapted by various users.
A famous example is the Bernie Sanders
mitten meme. A trope is a recurring theme or literary device used in
storytelling that audiences immediately recognize. It is a figure of speech. In advertising the tropes may be less
explicit. Some examples include a white
coat expert speaking authoritatively about a product, the
suggestion that a product either directly or indirectly makes you more
attractive or successful, or the suggestion that a product makes you more
savvy or competent.
Here is a direct comparison between memes and tropes across
key cultural and linguistic dimensions (1).
Considering all of the dimensions and
definitions the chemical imbalance theory is possibly one of the most
effective advertising tropes ever used. At
the time that the first SSRIs and SNRIs were approved by the FDA, all of the
companies involved were focused on this trope.
From my original post the chemical imbalance theory was also
referred to when bupropion was marketed in the negative sense that it was
“non-serotonergic” and had “minimal risk of sexual dysfunction”. Some of the ads included a rough scorecard of
receptor activity. These medications
were being marketed like potential customers were neurochemists and the
mechanism of action of the medications were known. As noted in the core definition in the
above table, the figurative language of chemical imbalance is a shortcut
to bypass a very complex process.
An additional consideration of an
advertising trope is that it can also be turned into a meme and I think this
occurred. In those pre-Internet days, early SSRI advertising overlapped with
National Depression Screening Day. Exposure of attendees and physicians at that
screening was thorough and people in the community were being exposed to the
same trope in TV and magazine ads. It
was not long before I started to encounter patients in the late 1990s that
wanted to know if they had a chemical imbalance.
The academic literature at the time did
not reflect the term and has not ever since.
The originators
of the monoamine hypothesis of depression were much more circumspect –
considering depression to be a complex multifactorial disorder that could not
be explained by a simple change in monoamines. Since that era there have been
over 100 hypotheses about depression with many carried forward to current
times. The serotonin
based theories of depression have faded rapidly over the past 2 decades
even though serotonergic systems are important for brain function and
sophisticated in vivo monitoring has shown that antidepressants of
several classes all
increase extraneuronal serotonin levels.
As noted in the above link, Charney and Nestler’s text currently
aggregates depression hypotheses under neurotrophic, immune, and neuroendocrine
headings. The specifics at this point
are lacking and since depression is a heterogenous condition with multiple
known medical and substance induced etiologies it will take subtypes that are
clearly defined by more than written criteria.
At some point I hope to provide a more detailed map, but for now I will get
back to the trope rather than the science.
The detractors of psychiatry can always
be counted upon to throw a trope at the wall and see what sticks. What better trope to use than a wildly
successful one from Pharma marketing?
Just add that psychiatrists are intellectually dishonest and are just
selling pharmaceuticals like drug companies and pretending to know the cause of
depression and the mechanism of action of antidepressants. You might even
extend that rhetoric to suggest that psychiatrists need to cling to that
certainty in order to legitimize themselves in medicine.
Is any of that rhetoric legitimate?
First, all FDA approved package inserts have a Mechanism of Action
section. For many medications that
section has a complete or provisional statement about the mechanism of action
being unknown (14-18). In the case of antidepressants,
the mechanism of action is generally listed as involving monoaminergic
transporters or receptors at some level.
Second, in reviews of drug targets in general antidepressant and
antipsychotic medications are listed with respective targets like most other
medications in clinical use (19). Third,
and most importantly – there is a tendency to think of rhetoric, memes, tropes,
and metaphor as being limited to arts and literature. Cognitive scientists and linguists view these
dimensions as the foundational mechanics of human communication and there is
ample evidence that they are used in every discipline – including medicine and
science.
At least part of the issue is that
tropes, memes, and metaphors are not really part of the mainstream of medical
or scientific literature. Nothing will be found in neurology, psychiatry, or
even neuroscience texts. It is generally
covered by linguists or researchers who identify as both linguists and
cognitive psychologists. That literature is useful to read because of the
overlap with cognitive psychology and also how these foundational mechanics of
language are used on a daily basis. It
provides an additional dimension for analysis of the literature in your primary
field. It goes beyond language disorders and aphasias noted in medical
practice.
The following table is a compilation of
the current theories of metaphor – since that is the basis for many (but not
all) tropes. It shows how metaphors are
theoretically more or less efficient and the main mechanism of action. Interestingly the suggested mechanisms are
basically processing metaphors. In
reading about modern theories of metaphors, it is clear that the landscape has
changed to one that sees much human communication as being dependent on
metaphors and the line between literal and figurative language as being much less
clear. Beyond that metaphors are seen as
foundational cognitive mechanisms rather than just linguistic or literary
devices.
In Conceptual Metaphor Theory (CMT) the mapping is a simplified or mechanistic view of the brain is mapped onto a complex (multifactorial/multidimensional) emotional state. Once that is established the result is reasoning from that state suggests that correcting the imbalance with correct the associated stated. The cognitive load is decreased because thinking about all of the real neuroanatomy and neurophysiology is not necessary. The reasoning is more like keeping your car full of gas or oil to keep it running.
Categorization Theory (CT) states that
two unlike categories are not mapped but instead a new superordinate category
is created. The example in this case
would be the category of things with mechanical or material deficiencies. This
category includes things that are depleted and in need of repair like broken automobiles
or vitamin deficiencies. The brain and
the car both do not work because of a material deficiency and once that is
identified they can be repaired.
Career of Metaphor Theory (COMT) says
that metaphors shift over time as they become more familiar. They start out as active comparisons as
suggested in the first two theories but eventually become their own
categorizations as dead metaphors.
A dead metaphor no longer requires the active comparison. For example,
early in the course chemical imbalance could be compared with another
deficiency diseases like diabetes, but as time goes on and it is more accepted
chemical imbalance is accepted as equivalent to depression without any imagination
of the chemistry involved.
Deliberate Metaphor Theory (DMT) draws
a distinction between metaphors that are used unconsciously and those that are introduced
deliberately. The intentional metaphors are more often used rhetorically. In this case, chemical imbalance was used
intentionally as a marketing device to explain or legitimize the use of
antidepressants. It also shifts
explanatory power away from environmental of psychological causes to biological
ones.
As I read about these theories, I
recalled the first time I was confronted with the chemical imbalance theory back in the 1980s. It was presented to
me by two pharmaceutical representatives. As a guy with considerable biochemistry and
chemistry experience my reaction was: “It sounds like you are saying the brain
is just a bag of chemicals.” They were
not very happy with me. But this
approach and the theory did not have any traction with me. There is concern within the science community
about the use of metaphor and the possible inadequacies. With chemical imbalance theory there are
several including: it does not adequately describe the level of complexity
involved, it does not accurately reflect the scientific literature, it creates
a level of certainty that does not exist, and it has led to a trope where it is
accepted at a political rather than a scientific level.
For all of these reasons, no
psychiatrist should be using this trope clinically. In the general population it is pervasive to
the point that I have talked with patients who tell me how they are trying to
correct their chemical imbalance. The people I am referring to have never seen a
psychiatrist and are trying to correct that imbalance by using street
drugs. They often have an elaborate schema
about how they can selectively increase various neurotransmitters to get
certain effects. They were shocked when I advised them that things don’t work
that way.
Returning to the reason for this post,
what is necessary to say to most people for adequate and ethical informed
consent. I have reviewed this in several
posts on this blog (20-26). Informed consent about both the diagnosis and
treatment intervention is critical and it needs to be adapted for the abilities
and preferences of every patient. When I
saw the reaction to the problems of the chemical imbalance trope being
countered by the suggestion that psychiatrist present more detailed neurobiological
information – I thought it reflected a lack of understanding of clinical reality
and here is why:
1:
It does not reflect what most people want. People come in to see psychiatrists at the
last possible moment. The people I saw over the course of my career had already
seen primary care physicians and therapists.
They were seeing me because nothing has worked. In some cases, they had specific concerns
about treatments or medications and wanted those concerns addressed initially. That is often the easiest unasked question.
2:
Discussing alternate treatments and a no treatment option. In the process I clarify my role as providing
the best possible advice based on current science.
3:
In the case of medications – discussing my experience with the
recommended medication including time course of response, typical side effects,
rare but serious side effects, and indications to call me. I also included a statement that most people
to wait too long to call or decide that they might “get used to” a side effect
but that I prefer they call me about it.
4:
A discussion of the therapeutic alliance, how that works, and the informed
consent aspects. This is often referred
to as “shared decision-making” these days.
I will always prefer the models of therapeutic alliance and informed consent
as a better fit for psychiatric practice.
5:
A discussion of other metaphors and tropes. There are many more out there today due to
the internet and popular science sites promoting them. Just a few examples – “rewiring your brain”, “neuroplasticity”,
“cleaning/cleansing your brain”, “reprogramming your brain”, brain as a "switchboard", brain regions as an "orchestra", need for brain "reset", brain as "hardware" amd mind as "software".etc. They are often used as a reason for diet, exercise,
branded psychotherapies, self help, etc. As far as I know none are used rhetorically and repeatedly
by antipsychiatry.
Effective treatment should be what the
informed consent decision is based on and that does not require that everyone
become a neuroscientist any more than receiving dental care requires everyone
to become an expert in teeth.
This post has been an interesting
excursion into linguistics, cognitive psychology, and rhetoric. I discovered and entire field of metaphorical
linguistics that I was unaware of.
Metaphor and simile are concepts right out of freshman English
composition – but the idea that metaphor is a cognitive process is much more
current. The progression of metaphors
over time is consistent with the conversion of episodic memory into semantic
memory. I have not been able to confirm
whether any of the metaphor theorists believe that at this point or whether it
has been written down anywhere. I do encourage
caution in using metaphors in psychiatry and agree with Kendler’s
thesis that we do not need to avoid biological reality in discussions with
patients. At the same time Kendler saw the need for metaphorical brain talk as arising
out of the need for a brain focus combined with an explanatory gap, status
anxiety over a clear underlying pathology, and a wish that we may eventually
get to the deeper understanding of the brain that we all seek. This missing piece is from linguistic theory
that metaphor is a basic cognitive mechanism that we all use and the evidence
is all of the depression tropes well beyond chemical imbalance at this
point.
In conclusion, meme, trope or metaphor chemical
imbalance has utility from a linguistic perspective and that may be why it
persists at a rhetorical level today.
There is also overlap with the goals of that rhetoric as pejorative and
I would argue it has attained dead metaphor status in that regard and therefore
not a term any psychiatrist should use.
George Dawson, MD, DFAPA
Supplementary 1:
If you are a cognitive psychologist or linguist - I am interested in references that you would consider state of the art about the role of metaphor in cognition.
Supplementary 2:
This post reminded me that as a senior psychiatry resident, I was fortunate enough to have and office down the hall from two speech and language pathologists. We had many great discussions about language, speech, and cognition. That happened at the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin.
References:
1:
Animétudes. Postmodern Media :
Memes and Database Consumption. May 3,
2020: https://animetudes.com/2020/05/03/postmodern-media-memes-and-database-consumption/
2: Kole M. Science fiction tropes: a guide for
writers. Good Story Company. October 2019:
https://www.goodstorycompany.com/science-fiction-tropes
3:
Everywriter R. 100 science
fiction tropes. Everywriter May4, 2024: https://www.everywritersresource.com/100-science-fiction-tropes/
4:
TV Tropes. Science fiction: https://tvtropes.org/pmwiki/pmwiki.php/Main/ScienceFiction
5:
Taylor C, Dewsbury BM. On the problem and promise of metaphor use in
science and science communication. Journal of microbiology & biology
education. 2018 Mar;19(1):10-128.
6:
Bradie M. Science and metaphor. Biology and Philosophy. 1999
Apr;14(2):159-66.
7:
Reynolds AS. Understanding metaphors in the life sciences. Cambridge
University Press; 2022 Apr 28.
8:
Mahootian F. Metaphor in chemistry: An examination of chemical metaphor.
In: Philosophy of Chemistry: Growth of a New Discipline 2014 Oct 19 (pp.
121-139). Dordrecht: Springer Netherlands.
9:
Muller CH, Rau MA. Instructional analogies dominate, domain-inherent
metaphors are overlooked: A systematic review of metaphorical mappings in
chemistry education. Journal of Chemical Education. 2025 Jun 6;102(7):2576-91.
10:
Rodriguez X, Arroyo-Santos A. The function of scientific metaphors: An
example of the creative power of metaphors in biological theories. InThe paths
of creation. Creativity in science and art 2011 Jan (Vol. 9, pp. 81-96). Peter
Lang Publishing Group Bern.
11:
Swiatczak B. Understanding life through metaphors: Andrew S. Reynolds:
Understanding metaphors in the life sciences. Cambridge: Cambridge University
Press, 2022, xx+ 200 pp,£ 11.99 PB.
12:
Veit W, Ney M. Metaphors in arts and science. European Journal for
Philosophy of Science. 2021 Jun;11(2):44.
CT doesn’t mean all metaphors in science are legitimate.
Just like some metaphors in artistic works are bad in various ways – bland,
tasteless, confusing,etc. – some in science might be bad. Neither does it imply
that the same criteria need to be used in evaluating metaphors in science as in
the arts.
13:
Fernyhough C. Metaphors of the
mind. British Psychological
Society. The Psychologist. June 18, 2006: https://www.bps.org.uk/psychologist/metaphors-mind
14:
FDA Package Insert: nortriptyline.
The mechanism of mood elevation by tricyclic
antidepressants is at present unknown. Pamelor is not a monoamine oxidase
inhibitor. It inhibits the activity of such diverse agents as histamine,
5-hydroxytryptamine, and acetylcholine. It increases the pressor effect of
norepinephrine but blocks the pressor response of phenethylamine. Studies
suggest that Pamelor interferes with the transport, release, and storage of
catecholamines.
15:
FDA Package Insert: fluoxetine.
Although the exact mechanism of PROZAC is unknown, it is
presumed to be linked to its inhibition of CNS neuronal uptake of serotonin.
16:
FDA Package Insert: venlafaxine.
The exact mechanism of the antidepressant action of
venlafaxine in humans is unknown, but is thought to be related to the
potentiation of serotonin and norepinephrine in the central nervous system,
through inhibition of their reuptake. Non- clinical studies have demonstrated
that venlafaxine and its active metabolite, ODV, are potent and selective
inhibitors of neuronal serotonin and norepinephrine reuptake and weak
inhibitors of dopamine reuptake.
17:
FDA Package Insert: bupropion.
The exact mechanism of the antidepressant action of
bupropion is not known, but is presumed to be related to noradrenergic and/or
dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the
neuronal reuptake of norepinephrine and dopamine, and does not inhibit the
reuptake of serotonin. Bupropion does not inhibit monoamine oxidase.
18:
FDA Package Insert: vortioxetine.
The mechanism of the antidepressant effect of vortioxetine
is not fully understood, but is thought to be related to its enhancement of
serotonergic activity in the CNS through inhibition of the reuptake of
serotonin (5-HT). It also has several other activities including 5-HT3 receptor
antagonism and 5-HT1A receptor agonism. The contribution of these activities to
vortioxetine’s antidepressant effect has not been established.
19:
Santos R, Ursu O, Gaulton A, Bento AP, Donadi RS, Bologa CG, Karlsson A,
Al-Lazikani B, Hersey A, Oprea TI, Overington JP. A comprehensive map of
molecular drug targets. Nat Rev Drug Discov. 2017 Jan;16(1):19-34. doi:
10.1038/nrd.2016.230. Epub 2016 Dec 2. PMID: 27910877; PMCID: PMC6314433.
20:
The Spectrum of Caring About Medication Information: https://real-psychiatry.blogspot.com/2014/05/the-spectrum-of-caring-about-medication.html
21:
Vigilance Is Required for Adequate Informed Consent: https://real-psychiatry.blogspot.com/2019/04/vigilance-is-required-for-adequate.html
22:
The New Black Box Warning on Benzodiazepines: https://real-psychiatry.blogspot.com/2021/03/the-new-black-box-warnings-on.html
23:
The Problem of Antidepressant Discontinuation: https://real-psychiatry.blogspot.com/2018/06/the-problem-of-antidepressant.html
24:
2000 Words About the Last Ten Minutes of a Psychiatric Evaluation: https://real-psychiatry.blogspot.com/2019/07/2000-words-about-last-ten-minutes-of.html
25:
Therapeutic Alliance - A Better Diagram:
https://real-psychiatry.blogspot.com/2017/09/therapeutic-alliance-better-diagram.html
26: Components of Patient Outcome: https://real-psychiatry.blogspot.com/2018/10/components-of-patient-outcome.html
