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Antidepressants and the Chemical Imbalance have assumed that they were hearing real
science, and not metaphor. Goodman’s
Theory of Depression: A Reflection and Update public statement raised the question: How
are patients with both diabetes and depres-
on the Discourse sion who listen to their doctor’s explana-
tion of their two conditions supposed to
know that one explanation is based on sci-
Jeffrey R. Lacasse, Florida State University entific measurement, and one is just a
Jonathan Leo, Lincoln Memorial University metaphor?
Table 1. Evidence the Chemical Imbalance Theory of Depression Is Not Valid: Selected Quotations
Quote Citation
“By 1970…[biochemist and Nobel Prize Winner Julius] Axelrod had concluded that, whatever was Healy, 2004, p. 12
wrong in depression, it was not lowered serotonin.”
“I spent the first several years of my career doing full-time research on brain serotonin metabolism, Lacasse & Gomory, 2003, p. 393
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 sero-
tonin research in the 1970s).
“Tianeptine is an interesting compound with antidepressant activity thought to be related to increased Ives & Heym, 1989, p. 22
rather than decreased 5HT [serotonin] uptake” [meaning, in 1989 it was known to be an antidepres-
sant that depletes, not increases, serotonin].
“The simplistic idea of the ‘5-HT [serotonin]’ neurone does not bear any relation to reality” (John Shorter, 2009, p. 204
Evenden, Astra pharmaceutical company research scientist, 1990).
“In the 1990s…No one knew if SSRIs raised or lowered serotonin levels; they still don’t know…There Healy, 2015
was no evidence that treatment corrected anything.”
“…Patients have been diagnosed with ‘chemical imbalances’ despite the fact that no test exists to sup- Kaiser, 1996; Lynch, 2015,
port such a claim, and there is no real conception of what a correct chemical imbalance would look pp. 31-32.
like…Yet 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 any-
thing now that has the stamp of approval of medical science” (Psychiatrist David Kaiser of
Northwestern University Hospital, 1996).
“Although it is often stated with great confidence that depressed people have a serotonin or norepi- Valenstein, 1998, p. 100
nephrine deficiency, the evidence actually contradicts these claims” (Neuroscientist Elliot Valenstein).
“The monamine hypothesis…holds that monoamines…such as… [serotonin]…are deficient in Dubvosky & Buzan, 1999,
depression and that the action of antidepressants depends on increasing the synaptic availability of p. 516
these monoamines….However, inferring neurotransmitter pathophysiology from…[SSRIs]…is simi-
lar to concluding that because aspirin causes gastrointestinal bleeding, headaches are caused by too
much blood…Additional experience has not confirmed the monoamine depletion hypothesis.”
(American Psychiatric Association Textbook of Psychiatry, 1999).
“A serotonin deficiency for depression has not been found” (Psychiatrist Joseph Glenmullen, Clinical Glenmullen, 2000, p. 197
Instructor of Psychiatry at Harvard Medical School).
“…I wrote that Prozac was no more, and perhaps less, effective in treating major depression than Kramer, 2002
prior medications….I argued that 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).
“[We must] abandon the simplistic hypotheses of there being either an abnormally high or abnormal- CINP Meeting with the Nobels
ly low function of a given neurotransmitter” (Avrid Carlson, Nobel Prize winner for his work on the (2003); Shorter, 2009, p. 204
neurotransmitter dopamine, 2002).
“Indeed, no abnormality of serotonin in depression has ever been demonstrated” (Psychiatrist and Healy, 2004, p. 12
historian David Healy in 2004).
Table 2. Promotion of the Chemical Imbalance Theory of Depression as Valid: Selected Quotations
“Celexa helps to restore the brain’s chemical bal- Celexa website, 2005 Lacasse & Leo, 2005
ance by increasing the supply of a chemical mes-
senger in the brain called serotonin.”
“Antidepressants may be prescribed to correct Let’s Talk Facts About Depression, a patient American Psychiatric
imbalances in the levels of chemicals in the brain.” information leaflet distributed by APA Association, 2005, p. 2
“Antidepressants…have no effect on normal Nada Stotland, president of the American Stotland, 2001, p. 65
mood. They restore brain chemistry to normal.” Psychiatric Association, 2007-2008
“[antidepressants work] only if there was a chemi- Donald Klein, psychiatrist and psychopharmacol- Talan, 1997
cal imbalance in the brain that needed fixing” ogist
“While the patient may require a somatic therapy Nancy Andreason, psychiatrist and author of The Andreason, 1985, p. 258
to correct the underlying chemical imbalance, he Broken Brain
may also need psychotherapy…”
“…some depressed patients who have abnormally Psychiatrist Richard Friedman in The New York Friedman, 2007
low levels of serotonin respond to SSRIs...” Times
“There is truly a real deficiency of serotonin in Psychiatrist Charles Nemeroff Nemeroff, 2007
depressed patients.”
“The physician should stress that depression is a MacArthur Foundation Depression Education Cole, Raju, Barrett, Gerrity, &
highly treatable medical illness caused by a chemi- Program for Primary Care Physicians Dietrich, 2000, p. 340
cal imbalance.”
“Patients with neurotransmitter dysregulation may Madkur Trivedi, psychiatrist at University of Trivedi, 2004, p. 13
have an imbalance of serotonin and norepineph- Texas Southwest Medical School, in The Primacy
rine…duloxetine [Cymbalta] may aid in correct- Care Companion of the Journal of Clinical
ing the imbalance of serotonin and norepineph- Psychiatry
rine neurotransmission in the brain.”
“Restoring serotonin’s imbalances not only helps Michael Thase, psychiatrist and psychopharmacol- Thase & Lang, 2004, p. 106
brighten mood and restore normal sleeping and ogy researcher at the University of Pennsylvania,
eating patterns, but it also seems to promote a and science writer Susan Lang
sense of well-being.”
“We now know that mental illnesses—such as Richard Harding, president of the American Harding, 2001, p. 66
depression or schizophrenia—are not ‘moral Psychiatric Association, 2000-2001
weaknesses’ or imagined but real diseases caused
by abnormalities of brain structure and imbal-
ances in chemicals of the brain….medications and
other treatments can correct these imbalances.
Talk therapy can directly improve brain function-
ing.”
“At some time in the course of their illness, most Robert Freedman, psychiatrist at the University of Freedman, 2003, as cited by
patients and families need some explanation of Colorado Hickey, 2014
what has happened and why. Sometimes the
explanation is as simplistic as ‘a chemical imbal-
ance’….”
LET TER TO THE EDITOR ogize for the confusion. We are glad that
we and Dr. Pies have this opportunity to
Response to Daniel Carlat (2015) correct the record.1 We note that a correc-
tion has been made to Dr. Pies’ original
and Ronald Pies (2015) article as of November 4, 2015 (Pies, 2014).
On Promotion of Psychiatric Drugs
Jeffrey R. Lacasse, Florida State University Like many, we believe that academic
psychiatrists have been too closely aligned
Jonathan Leo, Lincoln Memorial University–deBusk College of with the pharmaceutical companies (e.g.,
Healy, 2004). In our article, we hypothe-
Osteopathic Medicine sized, as we had before (Lacasse & Leo,
2009), that the flow of money from drug
companies to academic psychiatry might
Response to Daniel Carlat (2015) published content similar to that be partially responsible for the resounding
reported in the NPR interview) silence in academia regarding misleading
In our recent article (Lacasse & Leo,
advertising of psychiatric drugs. Dr. Pies
2015), we transcribed public statements
We don’t think scientific truth is so had himself argued that pharmaceutical
made by Dr. Carlat on National Public flexible, and disagree with shaping it for companies were responsible for spreading
Radio (NPR). Dr. Carlat disclosed that he purposes convenient to the prescriber (e.g., the chemical imbalance metaphor. While
used content similar to the Zoloft market- to get patients to take medication, or to we agreed that this was part of the problem
ing campaign (Lacasse, 2005) to explain reassure the patient of the prescriber’s (Lacasse & Leo, 2005), we saw some irony
antidepressants to patients: expert knowledge). Dr. Carlat also writes in the fact that he had received funding
that he boosts the placebo effect by telling from GlaxoSmithKline, among the worst
I’ll often say something like the way patients that SSRIs are “a very effective offenders in our opinion when it came to
Zoloft works, is, it increases the level of medication” (Carlat, 2015; this issue, p. misleading consumer advertising. We
serotonin in your brain (or synapses, 262). Fournier et al. (2010) demonstrated never accused Dr. Pies of acting in bad
neurons), and, presumably, the reason a Number-Needed-to-Treat (NNT) of 11 faith, and in fact wrote, “We want to be
you’re depressed or anxious is that you for severely depressed patients. In other clear that we are not accusing Dr. Pies of
have some sort of a deficiency. And I say words, when prescribing to 11 severely anything” and that entanglements with
that [chuckles] not because I really depressed patients, a prescriber would drug companies aren’t “uncommon
believe it . . . I think I say that because expect 1 to have an impressive short-term among academic psychiatrists, and some
patients want to know something . . . . response as compared to placebo. Given would say it was par for the course in the
They certainly don’t want to know that the existence of such data, we question the 2000s” (Lacasse & Leo, 2015, p. 209). How-
a psychiatrist essentially has no idea ever, Dr. Pies strongly objects to our asser-
accuracy of claiming that antidepressants
how these medications work. (Davies, tion that he has been involved in the pro-
are “very effective” (see also Weitz et al.,
2010) motion of psychiatric drugs, and so we will
2015).
reluctantly respond.
Despite Dr. Carlat’s allegation, we are Response to Ronald Pies (2015) How Psychiatric Drugs Are Promoted
not the serotonin thought police, ticketing As background, it is useful to under-
offenders that violate our sensibilities. But, On the “Little White Lie” of Chemical
stand the strategies that pharmaceutical
we don’t believe we’re alone in thinking it’s Imbalance companies use to promote2 their products.
objectionable to tell patients something In his reply, Dr. Pies (2015; this issue) They often contract with “medical com-
you don’t believe yourself. To say things states that he does not endorse calling the munications companies,” which specialize
like this publicly and not expect criticism chemical imbalance a “little white lie,” and in “publication planning” and employ
seems naïve. We are not cherry-picking that he was referencing Mr. Robert medical writers who contribute to (or even
here, as Dr. Carlat has a history of such dis- Whitaker when he used this phrase. We author or co-author) peer-reviewed arti-
closures: take his word on this, appreciate that he cles (Lacasse & Leo, 2010), usually with
acknowledges his editorial error, and apol- academics listed as authors on the byline
While it is true that most of our drugs
affect neurotransmitters in various 1 Inhis 2014 article, Dr. Pies begins a paragraph by citing an interview of Mr. Robert Whitaker
ways, when psychiatrists start using (Levine, 2014; Pies, 2014). Dr. Pies then writes about the “antipsychiatry movement.” In these
what I call neurobabble, beware, sentences there are no quotations and no citations; they consist of Dr. Pies’ own interpretations.
because we rarely know what we are He mentions chemical imbalance, writing that “by promoting this little white lie…” Mr.
talking about. I fall into this habit with Whitaker had used quotation marks around the phrase as editorial comment, but Dr. Pies did
patients all the time. When I find myself not. Without quotation marks or citation, we took this as we did his other writing in this section,
as his opinion (we aren’t the first to do so; see Hickey, 2014). We reproduced the entire quota-
using phrases like “chemical imbalance”
tion from Dr. Pies in a footnote, commenting on this exact issue (Lacasse & Leo, 2015, p. 209). A
and “serotonin deficiency,” it is usually correction to the article (Pies, 2014) was made in November of 2015, after our article was pub-
because I’m trying to convince a reluc- lished. Rather than clarifying where the phrase “little white lie” came from, Dr. Pies removed it
tant patient to take a medication . . . and replaced it with “simplistic formulation.” Interestingly, Mr. Whitaker did not characterize
(Carlat, 2010, p. 75; see pp. 74–83 for chemical imbalance as “simplistic” (Levine, 2014).
■ CLASSIFIED
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FELLOWSHIPS IN ADVANCED Applicants who have earned an M.D.,
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includes basic research in schizophrenia, Equal Opportunity/Affirmative Action
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