leo antidepressantsandthechemicalimbalance ... · levine, 2014). for instance, alan frazer,...

A DECADE AGO, WE PUBLISHED an articlein PLoS Medicine about the serotonin defi-ciency theory of depression (Lacasse & Leo,2005). We transposed the psychiatric liter-ature on serotonin and depression withwhat pharmaceutical companies had beenclaiming in their consumer advertisementsfor years—that a chemical imbalance (sero-tonin deficiency) caused depression andthis imbalance was corrected by selectiveserotonin reuptake inhibitor (SSRI) drugs.For instance, advertisements for fluoxetine(Prozac) had stated:

When you’re clinically depressed, onething that can happen is the level of sero-tonin (a chemical in your body) may drop.So you may have trouble sleeping. Feelunusually sad or irritable. Find it hard toconcentrate. Lose your appetite. Lackenergy. Or have trouble feeling plea-sure…to help bring serotonin levels closerto normal, the medicine doctors now pre-scribe most often is Prozac® (Eli Lilly,1998)

We knew that such advertisements didnot accurately reflect the scientific status ofthe serotonin theory in the psychiatricresearch community (see Table 1; we havemodified the original table to integrate newmaterial that came to our attention since2005). Some advertisements were moretentative or clever in their wording thanothers, but it seemed obvious that the drugcompanies were at least pushing theboundaries. We thought several of themwere going over the line, in plain sight ofthe Food and Drug Administration (FDA),which ostensibly regulates direct-to-con-sumer advertising. Our goal was to illus-trate the clear disconnect between theexisting psychiatric science and what thepublic was being told in these advertise-ments, and we argued that the FDA shouldissue warning letters to pharmaceuticalcompanies (Lacasse, 2005; Lacasse & Leo,2005). Of course, there were ramificationsfor clinicians—if it was illegal to claim thisin advertisements, wasn’t it also an unac-

ceptable thing to be telling vulnerableclients?

After the publication of the paper, wewere interviewed by numerous journalists.Several of them thought our work wasprovocative and that we were “attacking” awell-accepted theory. If it was an attack, itwas an inside job, as our sources includedNIMH-funded scientists, an award-win-ning biological psychiatrist, and a popularpsychiatric textbook. Anyone familiar withthe history of serotonin research wouldfind our argument unremarkable (e.g.,Healy, 1997, 2004; Moncrieff, 2008; Valen-stein, 1998). In the United Kingdom, psy-chiatrist David Healy has been making thispoint for decades (e.g., Healy, 1987, 1997,2004, 2012, 2015). But the questions fromjournalists reminded us that the enormousmarketing campaigns promoting SSRIdrugs (and surely many of the physiciansprescribing them) had convinced the U.S.public that the serotonin theory of depres-sion was firmly grounded in science. Thiswasn’t just an issue of misleading advertis-ing. Instead, the incredulity seemed fueledby the significant number of mental healthclients who had heard the chemical imbal-ance explanation from their prescribers.

We urged these reporters to query theFDA, American Psychiatric Association(APA), NIMH, and other official organiza-tions about the science behind the adver-tisements. New Scientist interviewedWayne Goodman, at the time a Universityof Florida psychiatrist and Chair of theFDA Psychopharmacological Committee.Dr. Goodman called the serotonin theory“a useful metaphor”—but one he neverused when informing his own patients,stating, “I can’t get myself to say that”(Lacasse & Leo, 2006; New Scientist, 2005).One has to expect that patients whose doc-tors had said that found this news upset-ting.

Serotonin imbalance as metaphor isobviously a deep problem for many of thepatients who have heard their physiciansexplain that their depression is caused by achemical imbalance. These patients must

have assumed that they were hearing realscience, and not metaphor. Goodman’spublic statement raised the question: Howare patients with both diabetes and depres-sion who listen to their doctor’s explana-tion of their two conditions supposed toknow that one explanation is based on sci-entific measurement, and one is just ametaphor?

The Problematic AdvertisementsDisappear

In the early 2000s, the serotoninmetaphor of depression was widely adver-tised by the makers of antidepressants,including advertisements for citalopram,escitalopram, fluoxetine, paroxetine, andsertraline (Lacasse & Leo, 2005). In partic-ular, Zoloft (sertraline) advertisements fea-turing the miserable ovoid creature wereunavoidable in U.S. television and maga-zines. An on-line repository of direct-to-consumer advertisements for psychiatricdrugs lists many from 1997–2007 referringto a chemical imbalance, across manydrugs and diagnostic categories (Hansen,2015a, 2015b).

A 2010 study compared on-line drugadvertising of antidepressants regardingthe issue of chemical imbalance in both2004 and 2009 (Lacasse & Hughes, 2010).The number of websites making suchclaims dropped, with some websites goingdark or minimalist as the drug patents ranout. Interestingly, some on-patent drugwebsites had simply removed the chemicalimbalance claims. Newer medications werepromoted as “adjusting” or “affecting”neurotransmitter levels, in contrast to “cor-recting a chemical imbalance.”

From 2014–2015, we collected furtherdata, finding that the simplistic narrative ofchemical imbalance that was so commonin direct-to-consumer advertising in the2000s is not widespread any longer. Con-sumers are no longer informed that antide-pressants will normalize their neurotrans-mitter levels. The Abilify thermostat isgone (Lacasse & Leo, 2006) and drugs arenow advertised as “affecting” neurotrans-mitters. This is mostly true for other classesof medications as well, as advertisementsfor psychostimulants (Leo & Lacasse, 2009)have also moderated their language sub-stantially. While we still see problematicadvertisements, the overall situation hasobviously improved.

There is no public explanation for whythis happened. To our knowledge, FDA hasnever sent a warning letter to a pharmaceu-tical company over claims that antidepres-

Antidepressants and the Chemical ImbalanceTheory of Depression: A Reflection and Updateon the DiscourseJeffrey R. Lacasse, Florida State UniversityJonathan Leo, Lincoln Memorial University

206 the Behavior Therapist

L A C A S S E & L E O

sants correct a chemical imbalance. In ourassessment, the promotion of chemicalimbalance theory in advertisements forSSRI drugs was wildly successful for thedrug companies and the psychiatric profes-sion alike. While it’s difficult to imaginethat they pulled them arbitrarily, we don’tknow why they largely disappeared.

By roughly 2007, anyone who Googled“serotonin and depression” could easilyfind articles explaining the mythical natureof serotonin imbalance, or at least the argu-ment. We don’t claim that our one littlearticle was responsible, or even original(see Breggin, 1998; Glenmullen, 2000;Healy, 1997, 2004). But given that thepublic had accepted the serotonin theory asfact (Pescosolido et al., 2010), the wide-spread public criticism of it and emergingtransparency of information on the Inter-net would obviously create problems, or atleast a dilemma. Below, we highlight a fewexamples of the recent discourse on theseissues (see also Levine, 2014; Lynch, 2015;Whitaker, 2010, 2015; Whitaker & Cos-grove, 2015).

I Don’t Really Believe It,but I Say It to Patients Anyway

Psychiatrist Daniel Carlat is a practicingpsychiatrist, a clinical instructor at TuftsUniversity, and editor of The Carlat Psychi-atry Report, which we have read for years.On July 13, 2010, he appeared on NationalPublic Radio (NPR; Davies, 2010) to pro-mote his book, Unhinged (2010), in whichhe describes psychiatry as a profession incrisis. Carlat had received some attentionin The New York Times, candidly reportinghis experience pitching venlafaxine(Effexor) to other doctors as a paid consul-tant for Wyeth. He found himself “tweak-ing and pruning the truth to stay positiveabout the product” and eventually resigned(Carlat, 2007). We find that Carlat isunusually transparent, providing interest-ing insights into uncomfortable issues.

Carlat was asked what we know aboutpsychiatric medication. He responded:

What we don’t know, is we don’t knowhow the medications actually work in thebrain. . . . I’ll often say something like theway Zoloft works, is, it increases the levelof serotonin in your brain (or synapses,neurons), and, presumably, the reasonyou’re depressed or anxious is that youhave some sort of a deficiency. And I saythat [chuckles] not because I really believeit, because I know the evidence really isn’tthere for us to understand the mecha-

nism—I think I say that because patientswant to know something. And they wantto know that we as physicians have somebasic understanding of what we’re doingwhen we’re prescribing medications. Theycertainly don’t want to know that a psychi-atrist essentially has no idea how thesemedications work. (Davies, 2010)

This is surely a remarkable publicadmission. Carlat continues:

We’re in a paradoxical situation, I think,where we prescribe medications that dowork according to the trials. And yet asopposed to essentially all other branches ofmedicine, we don’t understand the patho-physiology of what generates mental ill-ness and we don’t understand exactly howour medications work. (Davies, 2010)

A practicing psychiatrist could under-standably report that they see the medica-tions working in their practice and findthem useful. Invoking the clinical trials isperhaps a strange direction to go here,because the consistent lack of differencebetween SSRI and placebo in the clinicaltrial literature is one of the most com-pelling arguments against the serotonindeficiency theory. So Carlat is aware of theclinical trials, which essentially refute theserotonin theory, yet still tells patients thatthey have a serotonin imbalance. Andwhile some prescribers of psychiatric med-ication object to misleading SSRI advertise-ments (Rickels, 2006), Carlat sees wide-spread pharmaceutical propaganda as anopportunity:

One thing that has happened is thatbecause there’s been such a vacuum in ourknowledge about mechanism, the drugcompanies have been happy to sort of fillthat vacuum with their own version ofknowledge, that usually if you see a com-mercial for Zoloft on TV, you’ll be hearingthe line about serotonin deficiencies andchemical imbalances, even though wedon’t really have the data to back it up. Itbecomes a very useful marketing line fordrug companies, and then it becomes areasonable thing for us to say to patients togive them more confidence in the treat-ment they’re getting from us—but it maynot be true. (Davies, 2010)

Carlat’s straightforward admissions arelikely to cause reactions, and we think theymostly speak for themselves. It’s worthnoting that he sometimes frames the sero-tonin issue as one of scientific uncertainty:

we “essentially” or “exactly” don’t knowhow SSRI medications work, and the sero-tonin theory “may not be true.” Such state-ments need to be evaluated in light of theexisting literature (see Table 1). In fact, sci-entists have known for a long time that theserotonin theory presented by the drugcompanies and Carlat is not true (seeHealy, 2004, 2012, 2015; Lynch, 2015).Claiming scientific uncertainty about theissue could reflect a lack of familiarity withthe scientific literature, or a need to justifythe use of such statements. In our opinion,neither option is flattering or desirable inan era of shared clinical decision-making.The simple alternative would be to tellpatients the truth—that the pathophysiol-ogy of depression is unknown and that wehave no idea how SSRIs work.

The Positive Aspectsof Misinformed Thinking

On January 23, 2012, NPR MorningEdition aired “When it Comes to Depres-sion, Serotonin Isn’t the Whole Story”(Spiegel, 2012). While Carlat states that theserotonin theory “may not be true,” psychi-atrist Joseph Coyle makes a much clearerstatement: “I don’t think there’s any con-vincing body of data that anybody has everfound that depression is associated to a sig-nificant extent with a loss of serotonin.”Yet part of the segment focuses on the pos-itive aspects of telling patients that a sero-tonin imbalance causes depression (seeLevine, 2014). For instance, Alan Frazer,Professor of Pharmacology and Psychiatry,stated that the serotonin theory allowedpatients to:

Feel better about themselves if there wasthis biological reason for them beingdepressed, some deficiency, and the drugwas correcting it. They had a chemicalimbalance and the drug was correctingthat imbalance . . . yeah it’s like, I havedepression but I have a chemical imbal-ance, and you have hypothyroidism andyou have a chemical imbalance, and mychemical imbalance just happens to affectmy brain. (Spiegel, 2012)

Psychiatrist Pedro Delgado added,“When you feel that you understand it, a lotof the stress levels dramatically arereduced. So stress hormones and a lot ofbiological factors change.”

Not surprisingly, there were manyangry comments on the NPR website.Apparently, many psychiatric patientsnever realized they were hearing a

October • 2015 207

C H E M I C A L I M B A L A N C E

metaphor and not science. They didn’tknow that the chemical imbalancemetaphor was used in an attempt to reducestigma, or stress hormones, rather thanbeing accurate information presented bytheir trusted health-care provider. Sincechemical imbalance is often presented as arationale for taking SSRIs, some suchpatients now understandably feel lied to bytheir clinicians. Levine (2014) calls this“Psychiatry’s Manufacture of Consent.”

The claim that presenting the chemicalimbalance metaphor is in the best interestsof patients needs to be considered in lightof the existing empirical research. This infact is not what the literature shows (e.g.,Deacon & Baird, 2009). For instance, in arare controlled experiment on this topic,one group of depressed students were toldthey had a confirmed serotonin imbalanceunderlying their depression, while a con-trol group was not (Kemp, Lickel, &Deacon, 2014). The group who was toldthey had abnormal serotonin levels foundmedication more credible than psy-chotherapy and expected it to be moreeffective. They also had more pessimismabout their prognosis and a lower per-ceived ability to regulate negative moodstates, yet experienced no reduction in self-blame. These results suggest that the chem-ical imbalance explanation may indeed behelpful in persuading patients to take med-ication but that this is likely accompaniedby undesirable effects. Data such as thisshould be a major part of the conversationregarding informed consent in psychiatry.

The Role of JournalismPerhaps the most interesting part about

both of these NPR pieces is that neitherreporter questioned the experts about theethics of telling a falsehood to patientsbecause you think it is good for them. Incontrast to how, say, a foreign-policyexpert might be grilled on NPR, the tonewas deferential and accepting. We wouldhave liked both reporters to have asked thefollowing questions: (a) Do you believe it isethical to present a falsified scientifictheory as a fact to a patient? (b) What arethe possible negative effects of doing so? (c)Should the information you tell yourpatients be consistent with the psychiatrictextbooks on your shelf? (d) How does itaffect the psychiatrist-patient relationshipwhen your patients look up serotoninimbalance on the Internet and concludethat they have been misled?

It Wasn’t Us, It Wasthe Drug Companies

Ronald Pies is a psychiatrist at TuftsUniversity and served as editor of theprominent trade journal Psychiatric Timesfrom 2007–2010. From 2011 on, heauthored several pieces on the chemicalimbalance issue, which we recommend(Pies 2011a, 2011b, 2014). These are avail-able on the web, cited frequently, and Piesis the most prominent figure in U.S. psy-chiatry to take up this issue publicly. Piesdoesn’t believe that the chemical imbalancemetaphor should be attributed to psychia-try:

. . . opponents of psychiatry . . . menda-ciously attribute the phrase [“chemicalimbalance”] to psychiatrists themselves . . .And yes [it has] been vigorously promotedby some pharmaceutical companies, oftento the detriment of our patient’s under-standing. . . . In truth, the “chemical imbal-ance” notion was always a kind of urbanlegend—never a theory seriously pro-pounded by well informed psychiatrists.(Pies, 2011a)

We suspect that Pies had no idea howmany of his fellow psychiatrists he wasthrowing under the metaphorical bus bymaking this claim. While we don’t knowexactly how many clinicians have told theirpatients they were suffering from a chemi-cal imbalance over the last 25 years, webelieve that the number is significant andconsequential. Among 237 psychology stu-dents, Frances, Lysaker, and Robinson(2007) found that 46% had heard thechemical imbalance explanation from aphysician. Empirical studies report use ofthe chemical imbalance theory by pre-scribers, including psychiatrists (e.g.,Cohen & Hughes, 2011; Schreiber & Har-trick, 2002; see also Acker, 2013). Also,over the years, we’ve been in touch withmany people who reported hearing “it’s achemical imbalance” from psychiatrists:people in our social circles; “consumers” atconferences; our students who work incommunity mental health settings; subjectsin our research (Lacasse, Lietz, Hayes,Rider & Hess, in press); and people whoemailed us in response to our work. And,one of the authors once worked with a tal-ented psychiatrist and heard this explana-tion given weekly. If Pies is correct, that’san awful lot of uninformed clinicians.

A Bumper-Sticker Sloganto Educate Patients

In subsequent articles Pies moderateshis tone and concedes that practicing psy-chiatrists may have used the chemicalimbalance explanation at times (Pies,2011b). He claims that it is the result ofoverbooked clinicians looking for quickexplanations to accompany medication,perhaps to reduce self-blame on the part ofpatients (he acknowledges that this maybackfire). He states:

My impression is that most psychiatristswho use this expression feel uncomfort-able and a little embarrassed when they doso. It’s kind of a bumper-sticker phase thatsaves time, and allows the physician towrite out that prescription while feelingthat the patient has been “educated.” (Pies,2011b)

To us, this sounds similar to what Carlatwas reporting. Pies also notes that acade-mic psychiatry hasn’t done a great job ofcommunicating with Primary Care Physi-cians (PCPs), who write most of the pre-scriptions for SSRIs. This might be seen asa question of priorities, because academicpsychiatry in general has done a highlyeffective job of convincing PCPs to diag-nose and treat depression with antidepres-sants.

Academic Psychiatry as SilentPartner in the Promotion

of Chemical ImbalancePies admits that both he and official

psychiatric associations should have donemore to dispel the chemical imbalancemyth (Pies, 2014). He adds that there “weresincere attempts to do just that, by severalprominent psychiatrists.” Unfortunately,he doesn’t provide any recent examples (hedoes cite Shildkraudtt & Kety, 1967). It iseasy to imagine that a single prominentacademic psychiatrist, authoring an Op-Edin The New York Times, could have set therecord straight on serotonin imbalancedecades ago. Yet, to our knowledge, no onedid so.

We have long been concerned abouthow conflicts-of-interest with the pharma-ceutical industry might shape the behavior(unconsciously or not) of academic psychi-atrists, including the promotion of thechemical imbalance metaphor. In 2009, wewrote about misleading direct-to-con-sumer advertising of psychostimulantssuch as Adderall, where the claims were at



least as misleading as SSRI advertisements(Lacasse & Leo, 2009). Noting the lack ofobjections to these advertisements fromwithin academic psychiatry, we asked, “Is itpossible that the flow of money from thepharmaceutical companies to influentialacademic psychiatrists . . . has brought withit a certain willingness to remain silent?”We doubt Ronald Pies would find this irra-tionally conspiratorial, or a crazy questionto ask—because we published this in Psy-chiatric Times (Editor: Ronald Pies, M.D.).

Thus, while we don’t know why RonaldPies himself didn’t speak out on the chem-ical imbalance issue decades ago, readersshould be aware of his past financial rela-tionship with pharmaceutical companies.He sounds vaguely critical of the drugindustry in his recent articles and neverdiscloses any history of financial conflicts-of-interest. However, Pies has receivedfunding from GlaxoSmithKline, AbbotLaboratories, and Jannsen Pharmaceuti-cals—the makers of Paxil, Wellbutrin,Lamictal, Depakote, and Risperdal (Chau-dron & Pies, 2003; Pies & Rogers, 2005).For years, Paxil and Wellbutrin wereadvertised as correcting a chemical imbal-ance in the brain. These three companieshave recently been fined a combined $6.7billion for illegal marketing of their prod-ucts.1 Pies has also consulted for Apothe-Com, a "Medical CommunicationsAgency” that “provides services to supportthe commercialization of new prod-ucts…[including]….publications plan-ning, [and] promotional communica-tions…” (Pharma Voice Marketplace,2015). While useful context, this isn’tuncommon among academic psychiatrists,and some would say it was par for thecourse in the 2000s. However, in a publicforum, more transparency is preferable.Pies blames the drug companies for run-ning misleading advertisements about

chemical imbalance, belatedly admits heshould have said something sooner, butfails to mention that he was paid to helpthem promote their products at the timethe advertisements were running.

It’s important to realize that organizedpsychiatry doesn’t always remain silent,such as when the interests of psychiatricprescribers and pharmaceutical companiesconverge. In the mid-2000s, press releasesendorsed by some of the most prominentpsychiatrists in the United States wereissued objecting to the FDA black boxwarning on SSRIs (e.g., American Collegeof Neuropsychopharmacology, 2006;Healy, 2012). The APA also issued a pressrelease defending antidepressants (APA,2004; Healy, 2006). This was at a time whenthe chemical imbalance metaphor wasomnipresent in direct-to-consumer adver-tising. While that was seen as a pressingissue to present to the public, misleadingmessages on chemical imbalance were not.

But We Never Promoted the TheoryRemaining silent is one thing, promot-

ing chemical imbalance theory is another.Pies has also stated, “I am not aware of anyconcerted effort by academic psychiatrists,psychiatric textbooks, or official psychi-atric organizations to promote a simplisticchemical imbalance hypothesis of mentalillness” (2014). In the age of the Internet, itdidn’t take long for MadinAmerica.comblogger Philip Hickey (2014) to make himaware of some. We added to the list by con-sulting Lynch (2015, Chapter 5) andsearching the Internet. The resulting list(Table 2) is admittedly incomplete but suf-ficient to address Pies’ point.

Clearly, mainstream psychiatry (includ-ing academic psychiatry and professionalorganizations) has promoted the chemicalimbalance theory. Comparing Table 1 andTable 2, it is apparent that there are often

two different conversations occurring(Whitaker, 2010; Whitaker & Cosgrove,2015). One is the actual scientific discourse,as exemplified in the APA’s Textbook ofPsychiatry (Hales, Yudofsky, & Talbott,1999), which accurately describes theempirical status of serotonin imbalancetheory 16 years ago. The other conversa-tion is between influential psychiatrists andthe public, or between psychiatrists andprimary care physicians. In this secondconversation, the drug company advertis-ing line about SSRIs correcting chemicalimbalances is repeated as fact by psychi-atric authorities, including the APA.

The Chemical Imbalance Theoryas a Little White Lie

Pies started out enthusiastically cri-tiquing the chemical imbalance theory. Weobviously believe he tried to rewrite somehistory along the way. But, by 2014, Piesrefers to the use of the chemical imbalancemetaphor as “a little white lie”2 (Pies, 2014;see also Hickey, 2014). While previouslypsychiatrists who used this language werenot well-trained, or knowledgeable, orwell-informed, now they are just tellingwhite lies—little ones.

We found this disappointing. When ourphysicians are educating us, we prefer theynot tell us any lies, white or otherwise.Unfortunately, characterizing the chemicalimbalance metaphor as a “little white lie”communicates a paternalistic, hierarchicalapproach that sounds suspiciously like thedays of medicine that we thought we hadleft behind. It’s a “little white lie” if you’re apsychiatrist; if you’re a confused, vulnera-ble depressed person who agrees to take anSSRI after hearing it, you might not con-sider it so little. After all, if your trustedphysician tells you that you have a chemicalimbalance in your brain that can be cor-rected with medication, not doing sosounds foolish, if not scary (Lacasse, 2005).How many patients with reservationsabout SSRIs have agreed to take medicationafter being told this “little white lie”?

DiscussionIn the last decade, widespread claims of

chemical imbalance in depression haveessentially been withdrawn by both theprofession of psychiatry and the pharma-ceutical industry. We believe the professionof psychiatry should be strongly critiquedfor withdrawing the serotonin theory belat-edly, long after the science was in, and fornot speaking up while drug advertisements

1We want to be clear that we are not accusing Ronald Pies of anything. Conflicts-of-interest areroutine in academic psychiatry and many of the major pharmaceutical companies have beenfined in the recent past. We do believe that readers deserve to know of his past financial rela-tionships with the drug companies that promoted their products as correcting a chemical imbal-ance. The details of these financial relationships are not publicly available.

2Pies’ (2014) original quote reads as follows: “In the narrative of the antipsychiatry movement, amonolithic entity called 'Psychiatry' has deliberately misled the public as to the causes of mentalillness, by failing to debunk the chemical imbalance hypothesis. Indeed, this narrative insists thatby promoting this little white lie, psychiatry betrayed the public trust and made it seem as if psy-chiatrists had magic bullets for psychiatric disorders.” It’s important to realize that “little whitelies” is Pie’s characterization of chemical imbalance, not how it is presented in the critical narra-tive. Writers like Whitaker (2010) vigorously critique the idea of chemical imbalance exactlybecause they do not see it as a “little white lie.”

October • 2015 209


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

“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, resultsfrom 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 increasedrather 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” (JohnEvenden, Astra pharmaceutical company research scientist, 1990).

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

“…Patients have been diagnosed with ‘chemical imbalances’ despite the fact that no test exists to sup-port such a claim, and there is no real conception of what a correct chemical imbalance would looklike…Yet conclusions such as ‘depression is a biochemical imbalance’ are created out of nothing morethan 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 ofNorthwestern University Hospital, 1996).

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

“The monamine hypothesis…holds that monoamines…such as… [serotonin]…are deficient indepression and that the action of antidepressants depends on increasing the synaptic availability ofthese monoamines….However, inferring neurotransmitter pathophysiology from…[SSRIs]…is simi-lar to concluding that because aspirin causes gastrointestinal bleeding, headaches are caused by toomuch 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, ClinicalInstructor of Psychiatry at Harvard Medical School).

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

“[We must] abandon the simplistic hypotheses of there being either an abnormally high or abnormal-ly low function of a given neurotransmitter” (Avrid Carlson, Nobel Prize winner for his work on theneurotransmitter dopamine, 2002).

“Indeed, no abnormality of serotonin in depression has ever been demonstrated” (Psychiatrist andhistorian David Healy in 2004).

Healy, 2004, p. 12

Lacasse & Gomory, 2003, p. 393

Ives & Heym, 1989, p. 22

Shorter, 2009, p. 204

Healy, 2015

Kaiser, 1996; Lynch, 2015,pp. 31-32.

Valenstein, 1998, p. 100

Dubvosky & Buzan, 1999,p. 516

Glenmullen, 2000, p. 197

Kramer, 2002

CINP Meeting with the Nobels(2003); Shorter, 2009, p. 204

Healy, 2004, p. 12

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

Quote Citation



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

Quote CitationSource

“Celexa helps to restore the brain’s chemical bal-ance by increasing the supply of a chemical mes-senger in the brain called serotonin.”

“Antidepressants may be prescribed to correct im-balances in the levels of chemicals in the brain.”

“Antidepressants…have no effect on normal mood.They restore brain chemistry to normal.”

“[antidepressants work] only if there was a chemi-cal imbalance in the brain that needed fixing”

“While the patient may require a somatic therapyto correct the underlying chemical imbalance, hemay also need psychotherapy…”

“…some depressed patients who have abnormallylow levels of serotonin respond to SSRIs...”

“There is truly a real deficiency of serotonin in de-pressed patients.”

“The physician should stress that depression is ahighly treatable medical illness caused by a chemi-cal imbalance.”

“Patients with neurotransmitter dysregulation mayhave an imbalance of serotonin and norepineph-rine…duloxetine [Cymbalta] may aid in correctingthe imbalance of serotonin and norepinephrineneurotransmission in the brain.”

“Restoring serotonin’s imbalances not only helpsbrighten mood and restore normal sleeping andeating patterns, but it also seems to promote asense of well-being.”

“We now know that mental illnesses—such as de-pression or schizophrenia—are not ‘moral weak-nesses’ or imagined but real diseases caused byabnormalities of brain structure and imbalances inchemicals of the brain….medications and othertreatments can correct these imbalances. Talk ther-apy can directly improve brain functioning.”

“At some time in the course of their illness, mostpatients and families need some explanation ofwhat has happened and why. Sometimes the expla-nation is as simplistic as ‘a chemical imbalance’….”

Celexa website, 2005

Let’s Talk Facts About Depression, a patientinformation leaflet distributed by APA

Nada Stotland, president of the American Psychi-atric Association, 2007-2008

Donald Klein, psychiatrist and psychopharmacolo-gist

Nancy Andreason, psychiatrist and author of TheBroken Brain

Psychiatrist Richard Friedman in The New YorkTimes

Psychiatrist Charles Nemeroff

MacArthur Foundation Depression Education Pro-gram for Primary Care Physicians

Madkur Trivedi, psychiatrist at University of TexasSouthwest Medical School, in The Primary CareCompanion of the Journal of Clinical Psychiatry

Michael Thase, psychiatrist and psychopharmacol-ogy researcher at the University of Pennsylvania,and science writer Susan Lang

Richard Harding, president of the American Psy-chiatric Association, 2000-2001

Robert Freedman, psychiatrist at the University ofColorado

Lacasse & Leo, 2005

American Psychiatric Associa-tion, 2005, p. 2

Stotland, 2001, p. 65

Talan, 1997

Andreason, 1985, p. 258

Friedman, 2007

Nemeroff, 2007

Cole, Raju, Barrett, Gerrity, &Dietrich, 2000, p. 340

Trivedi, 2004, p. 13

Thase & Lang, 2004, p. 106

Harding, 2001, p. 66

Freedman, 2003, as cited byHickey, 2014

October • 2015 211

CH EM I C A L I M B A L A NC E

(and many clinicians) were convincing theAmerican public that the chemical imbal-ance theory was legitimate. We previouslyargued that the propagation of misleadingadvertising “is only possible in the absenceof vigorous government regulation . . . oroutcry from professional associations”(Lacasse & Leo, 2006). That outcry nevercame, and these issues weren’t addressedpublicly until the patents for most block-buster SSRIs had expired, and Big Pharmamoved onto mood stabilizers and atypicalantipsychotics. While we are hesitant tooveremphasize conflicts-of-interest as anexplanation for what has occurred, we can’thelp but notice that the silence of psychia-try regarding chemical imbalance onlyended when the profits had been extractedfrom the SSRI marketplace.

The new narrative will apparently bethat psychiatrists recently discovered thatthe chemical imbalance theory was incor-rect. Psychiatric researchers are changingtheir mind based on data, so the story goes,and it just took a while to let the publicknow. We believe this is empirically incor-rect (Table 1; see Healy, 2015; Shorter,2015). The idea that the withdrawal of thechemical imbalance theory was caused byrecent data should be rejected.

As the theory has been withdrawn and adialogue has taken place, many mentalhealth clients have reacted negatively to thenews that there was never any reason tobelieve that depression was caused by aserotonin imbalance (Healy, 2015). Manymental health clients find it unacceptable,and perhaps a violation of ethical informedconsent, for clinicians to give patientsmetaphorical explanations for their mentalhealth problems and promote them as sci-entific truth. Patients who start an SSRIbecause they have been told it will correcttheir chemical imbalance, that it is like thy-roid medication for hypothyroidism, arelikely to eventually conclude that they havesimply not been told the truth. This obvi-ously creates awkward dynamics inpatient-prescriber relationships and alsorepresents a potential public relationsproblem for the profession of psychiatry.

Previously, we argued that misleadingconsumer advertisements for SSRIs shouldend (Lacasse & Leo, 2005). A decade later,the serotonin theory of depression isacknowledged to be dead, and most SSRIadvertising campaigns are now part of his-tory. We look forward to a day when tellingdepressed patients they have a serotoninimbalance is as anachronistic as the miser-able ovoid creature from the Zoloft adver-tisements of the past, and we believe that

day will come sooner than some might sup-pose. We encourage our colleagues in orga-nized psychiatry to work towards this endby improving medical education and ongo-ing training, by endorsing shared decision-making, and by ensuring that informedconsent is based on the scientific literature.

ReferencesAcker, J. (2013). Influences on social work-

ers’ approach to informed consent regard-ing antidepressant medication. Unpub-lished doctoral dissertation,SUNY-Albany, Albany, NY.

American College of Neuropsychophar-macology. (2006). Preliminary report ofthe task force on SSRIs and suicidalbehavior in youth. Neuropsychopharma-cology, 31, 473-492.

American Psychiatric Association. (2004,October 15). APA responds to FDA’s newwarning on antidepressants. NewsRelease.

American Psychiatric Association (2005).Let's talk facts about depression [patientleaflet].

Andreason, N.C. (1985). The broken brain:The biological revolution in psychiatry.New York: Harper and Row.

Breggin, P.R. (1998). Brain-disabling treat-ments in psychiatry: Drugs, electroshock,and the role of the FDA. New York:Springer.

Carlat, D.J. (2007, November 25). Dr. DrugRep. Retrieved August 13, 2015, fromhttp://www.nytimes.com/2007/11/25/magazine/25memoir-t.html?page-wanted=all

Carlat, D.J. (2010). Unhinged: The troublewith psychiatry – A doctor’s revelationsabout a profession in crisis. New York:Free Press.

Chaudron, L. H., & Pies, R. W. (2003).The relationship between postpartumpsychosis and bipolar disorder: A review.Journal of Clinical Psychiatry, 64(11),1284-1292.

Cohen, D., & Hughes, S. (2011). How dopeople taking psychiatric drug explaintheir “chemical imbalance?” EthicalHuman Psychology and Psychiatry, 13(3),176-189.

Cole, S., Raju, M., Barrett, J., & Gerrity, M.,& Dietrich, A. (2000). The MacArthurFoundation depression education pro-gram for primary care physicians: Back-ground, participant’s workbook, andfacilitator’s guide. General Hospital Psy-chiatry, 22, 299-358.

Davies, D. (2010). A psychiatrist’s prescrip-tion for his profession. [Interview].Retrieved from www.wbur.org/npr/128107547

Deacon, B.J. (2013). The biomedical modelof mental disorder: A critical analysis ofits validity, utility, and effects on psy-chotherapy research. Clinical PsychologyReview, 33(7), 846-861.

Deacon, B.J., & Baird, G.L. (2009). Thechemical imbalance explanation ofdepression: Reducing blame at what cost?Journal of Social and Clinical Psychology,28(4), 415-435.

CINP Meeting with the Nobels. (2003).Speakers notes: Dr. Avrid Carlson (June25, 2002). Collegium InternationaleNeuro-Psychopharmacologicum Newslet-ter, 5.

Dubvosky, S., & Buzan, R. (1999). Mooddisorders. In R. Hales, S.C. Yudofsky, &J.A. Talbott (Eds.)., Textbook of Psychia-try (3rd ed., pp. 479-565). Washington,DC: American Psychiatric Association.

Eli Lilly (1998, January). Prozac advertise-ment. People Magazine, 40.

Frances, C.M., Lysaker, P.H., & Robinson,R.P. (2007). The “chemical imbalance”explanation for depression: Origins, layendorsement, and clinical implications.Professional Psychology: Research andPractice, 38(4), 411-420.

Friedman, R.A. (2007). On the horizon,personalized depression drugs. Retrievedfrom http://www.nytimes.com/2007/06/19/health/psychology/19beha.html? pagewanted=print&_r=0 onAugust 15, 2015.

Glenmullen, J. (2000). Prozac backlash.New York: Simon and Schuster.

Hales, R., Yudofsky, S.C. & Talbott, J.A.(Eds.), Textbook of psychiatry (3rd ed.,pp. 479-565). Washington, DC: Ameri-can Psychiatric Association.

Hansen, B. (2015a). Depression madesimple. Retrieved August 27, 2015, fromhttps://web.archive.org/web/20150827093803/http://www.bonkersinstitute.org/simpledepress.html.

Hansen, B. (2015b). Anxiety and panicmade simple. Retrieved on August 27,2015, from https://web.archive.org/web/20150827094057/http://www.bonkersin-stitute.org/simpleanxiety.html.

Harding, R. (2001, November 20).Unlocking the brain’s secrets. FamilyCircle.

Healy, D. (1987). The structure of psy-chopharmacological revolutions. Psychi-atric Developments, 5(4), 349-376.

Healy, D. (1997). The antidepressant era.Cambridge, MA: Harvard University.

Healy, D. (2004). Let them eat Prozac: Theunhealthy relationship between the phar-maceutical industry and depression. NewYork: New York University.

Healy, D. (2006). The antidepressant tale:Figures signifying nothing? Advances inPsychiatric Treatment, 12,(5), 320-328.



Healy, D. (2012). Pharmageddon. Berke-ley: University of California.

Healy, D. (2015). Serotonin and depres-sion. BMJ, 350, h1771.

Hickey, P. (2014). Psychiatry DID promotethe chemical imbalance theory. RetrievedAugust 13, 2015, from http://www.madi-namerica.com/2014/06/psychiatry-pro-mote-chemical-imbalance-theory/.

Ives, J.L., & Heym, J. (1989). Antidepres-sive agents. Annual Reports in MedicinalChemistry, 24, 21-29.

Kaiser, D. (1996). Against biologic psychi-atry. Psychiatric Times, 8(12).

Kemp, J.J., Lickel, J.J., & Deacon, B.J.(2014). Effects of a chemical imbalancecausal explanation on individual’s per-ceptions of their depressive symptoms.Behaviour Research and Therapy, 56, 47-52.

Kramer, P. (2002, July 7). Fighting thedarkness in the mind. New York Times,8, 4.

Lacasse, J.R. (2005). Consumer advertisingof psychiatric medications biases thepublic against non-pharmacologicaltreatment. Ethical Human Psychologyand Psychiatry, 7(3), 175-179.

Lacasse, J.R., & Gomory, T. (2003). Isgraduate social work education promot-ing a critical approach to mental healthpractice? Journal of Social Work Educa-tion, 39(3), 383-408.

Lacasse, J.R., & Hughes, S. (2010, January).Discordance between evidence-based neu-roscience and direct-to-consumer adver-tising of antidepressants on the WorldWide Web: A five-year follow-up. Paperpresented at the 14th Annual Conferenceof the Society for Social Work andResearch, San Francisco.

Lacasse, J.R., & Leo, J. (2005). Serotoninand depression: A disconnect betweenthe advertisements and the scientific lit-erature. PLoS Medicine, 2(12), 101-106.

Lacasse, J.R., & Leo, J. (2006). Question-able advertising of psychotropic medica-tions and disease mongering. PLoS Medi-cine, 3(7), 1192.

Lacasse, J.R., & Leo, J. (2009). Consumeradvertisements for psychostimulants: Along record of misleading promotion.Psychiatric Times, 26(2). RetrievedAugust 25, 2015, from http://www.psychiatrictimes.com/articles/consumer-advertisements-psychostimulants-united-states.

Lacasse, J.R., Lietz, C.A., Hayes, M., Rider,A., & Hess, J.Z. (in press). The clientexperience of psychiatric medication: Aqualitative study. Social Work in MentalHealth.

Leo, J., & Lacasse, J.R. (2009). The manip-ulation of data and attitudes aboutADHD: A study of consumer advertise-

ments. In S. Tamimi & J. Leo (Eds.),Rethinking ADD: From brain to culture(pp. 287-312). New York: PalgraveMacmillan.

Levine, B. (2014, May 14). Psychiatry’smanufactured of consent. RetrievedAugust 15, 2015, from http://www.counterpunch.org/2014/05/14/psychiatrys-manufacture-of-consent/.

Lynch, T. (2015). Depression delusion:Themyth of the chemical imbalance. Limer-ick, Ireland: Mental Health Publishing.

Moncrieff, J. (2008). The myth of the chem-ical cure: A critique of psychiatric drugtreatment. New York: Palgrave-MacMil-lan.

Nemeroff, C.B. (2007). Advances in thebiology and treatment of depression.Retrieved August 15, 2015, fromhttp://www.medscape.org/viewarticle/553319.

New Scientist. (2005, 12 November). Tele-vision adverts for antidepressants causeanxiety. www.newscientist.com

Pescosolido, B. A., Martin, J. K., Long, J. S.,Medina, T. R., Phelan, J. C., & Link, B. G.(2010). A disease like any other? Adecade of change in public reactions toschizophrenia, depression, and alcoholdependence. The American Journal ofPsychiatry, 167, 1321–1330.

Pharma Voice Marketplace. (2015).ApotheCom entry. Retrieved September1, 2015, from http://www.pharmavoice-marketplace.com/view.php?com-pany=75506.

Pies, R.W. (2011a). Psychiatry’s new brain-mind and the legend of “Chemical Imbal-ance.” Retrieved August 13, 2015, fromhttp://www.psychiatrictimes.com/blogs/couch-crisis/psychiatry-new-brain-mind-and-legend-chemical-imbalance.

Pies, R.W. (2011b). Doctor, is my mooddisorder due to a chemical imbalance?Retrieved August 13, 2015, fromhttp://psychcentral.com/blog/archives/2011/08/04/doctor-is-my-mood-disorder-due-to-a-chemical-imbalance/

Pies, R.W. (2014). Nuances, narratives,and the “Chemical Imbalance” debate.Retrieved August 13, 2015, fromhttp://www.medscape.com/viewarticle/823368.

Pies, R.W., & Rogers, D. (2005). The recog-nition and treatment of depression: Areview for the primary care clinician.Retrieved September 3, 2015, fromhttp://www.medscape.org/viewprogram/4572.

Rickels, K. (2006). Consumer advertisingcan be misleading. PLoS Medicine, 3(2),e119.

Schreiber, R., & Hartrick, G. (2002). Keep-ing it together: How women use the bio-

medical explanatory model to managethe stigma of depression. Issues in MentalHealth Nursing, 23(2), 91-105.

Shorter, E. (2009). Before Prozac: The trou-bled history of mood disorders in psychia-try. New York: Oxford.

Shorter, E. (2015, April 27). The comingbattle over serotonin and depression. Howeveryone became depressed [PsychologyToday blog]. Retrieved August 25, 2015,from https://www.psychologytoday.com/blog/how-everyone-became-depressed/201504/the-coming-battle-over-serotonin-and-depression.

Spiegel, A. (2012). When it comes todepression, serotonin isn’t the whole story[NPR Morning Edition]. Retrieved fromhttp://www.npr.org/sections/health-shots/2012/01/23/145525853/when-it-comes-to-depression-serotonin-isnt-the-whole-story

Stotland, N.L. (2001, November 20).About depression in women. FamilyCircle.

Talan, J. (1997, November 17). The prolif-eration of Prozac. Los Angeles Times.Retrieved September 1, 2015, fromhttp://articles.latimes.com/1997/nov/17/health/he-54682/2.

Thase, M.E., & Lang, S.S. (2004). Beatingthe blues: New approaches to overcomingdysthymia and chronic mild depression.New York: Oxford.

Trivedi, M.H. (2004). The link betweendepression and physical symptoms. Pri-mary Care Companion of the Journal ofClinical Psychiatry, 6 [suppl. 1], 12-16.

Valenstein, E. (1998). Blaming the brain:The truth about drugs and mental health.New York: Free Press.

Whitaker, R. (2010). Anatomy of an epi-demic: Magic bullets, psychiatric drugs,and the astonishing rise of mental illnessin America. New York: Crown.

Whitaker, R. (2015). Chemical imbalances:The making of a societal delusion. In S.Olfman (Ed.)., The science and pseudo-science of children’s mental health (pp.11-22 ). Santa Barbara, CA: Praeger.

Whitaker, R., & Cosgrove, L. (2015). Psy-chiatry under the influence: Institutionalcorruption, social injury, and prescrip-tions for reform. New York: Palgrave-Macmillan.

. . .

Correspondence to Jeffrey R. Lacasse, [email protected]

October • 2015 213



neuroimaging biomarkers to achieveunprecedented levels of precision in pre-dicting individual patient outcomes follow-ing CBT (Doehrmann et al., 2013; Siegle etal., 2012). These are just a few examples ofan ongoing and iterative process of discov-ery in which neuroscience and clinical psy-chological science inform one another andcreate avenues for continuing to improveon the valuable tools psychologists alreadyhave at their disposal.

We enthusiastically welcome any of thecontributors to the special issue, as well asany readers who find the topic engaging, toattend our SIG meeting which occursannually at the ABCT convention. Themeeting will serve as a useful launchingpoint for ABCT members from all back-grounds to learn more about the possibili-ties our SIG members envision for transla-tional and neurocognitive research and toengage in an open dialogue around theseissues. We hope and expect that ABCT willcontinue to be a place where individualsutilizing diverse methodologies can learnfrom one another, united in the goal ofrelieving the suffering caused by psycho-logical conditions.

ReferencesDeacon, B., & McKay, D. (Eds.). (2015).

The biomedical model of psychologicalproblems [Special issue]. the BehaviorTherapist, 38(7).

De Raedt, R., Vanderhasselt, M. A., &Baeken, C. (2015). Neurostimulation asan intervention for treatment resistantdepression: From research on mecha-nisms towards targeted neurocognitivestrategies. Clinical Psychology Review, 41,61-69.

Doehrmann, O., Ghosh, S. S., Polli, F. E.,Reynolds, G. O., Horn, F., Keshavan, A.,. . . Gabrieli, J. D. (2013). Predicting treat-ment response in social anxiety disorderfrom functional magnetic resonanceimaging. JAMA Psychiatry, 70(1), 87-97.

Mohlman, J., Deckersbach, T., & Weiss-man, A. S. (Eds.). (2015). From symptomto synapse: A neurocognitive perspectiveon clinical psychology. New York, NY:Routledge.

Ressler, K. J., Rothbaum, B. O., Tannen-baum, L., Anderson, P., Graap, K.,Zimand, E., Hodges, L., & Davis, M.(2004). Cognitive enhancers as adjunctsto psychotherapy: Use of D-cycloserinein phobic individuals to facilitate extinc-tion of fear. Archives of General Psychia-try, 61, 1136-1144.

Rothbaum, B. O., Kearns, M. C., Price, M.,Malcoun, E., Davis, M., Ressler, K. J.,Lang, D., & Houry, D. (2012). Earlyintervention may prevent the develop-ment of posttraumatic stress disorder: Arandomized pilot civilian study withmodified prolonged exposure. BiologicalPsychiatry, 72(11), 957-963.

Schiller, D., Kanen, J. W., LeDoux, J. E.,Monfils, M. H., & Phelps, E. A. (2013).Extinction during reconsolidation ofthreat memory diminishes prefrontalcortex involvement. Proceedings of theNational Academy of Sciences, 110(50),20040-20045.

Siegle, G. J., Thompson, W. K., Collier, A.,Berman, S. R., Feldmiller, J., Thase, M. E.,& Friedman, E. S. (2012). Towards clini-cally useful neuroimaging in depressiontreatment: Is subgenual cingulate activityrobustly prognostic for depression out-come in Cognitive Therapy across stud-ies, scanners, and patient characteristics?Archives of General Psychiatry, 69(9),913-924.

. . .

Correspondence to Rebecca B. Price, Ph.D.,University of Pittsburgh, Department of Psy-chiatry, 3811 O'Hara St., Pittsburgh, PA15213; [email protected]

FOR THE PAST 33 YEARS as a psychiatrist,teacher, and writer, I have advocated acomprehensive, “biopsychosocial” modelof mental illness and its treatment. Indeed,my 1994 textbook was titled ClinicalManual of Psychiatric Diagnosis and Treat-ment: A Biopsychosocial Approach. There isoverwhelming evidence that biological andgenetic factors contribute to the risk ofdeveloping some psychiatric disorders,including but not limited to major depres-sive disorder (MDD) (Gold et al., 2015);however, psychological, social, and culturalfactors are also involved in the genesis ofmany psychiatric disorders, includingMDD (Compton & Shim, 2015). Hence, apurely “chemical imbalance theory” ofdepression or any mental disorder is sim-plistic, incomplete, and unhelpful when it

implies that psychosocial factors are unim-portant.

Unfortunately, in recent years, antipsy-chiatry bloggers have argued that “psychia-try”—in some broad, institutional sense—has promoted a “chemical imbalancetheory” of mental illness in general. I haveargued that there has been no such general“theory” propounded by academic psychi-atrists, psychiatric textbooks, or officialpsychiatric organizations, such as theAmerican Psychiatric Association. I standby that claim. On the other hand, most psy-chiatrists would acknowledge that the bio-genic amine hypothesis of affective disor-ders (Schildkraut & Kety, 2015) has indeedled many physicians to use the unfortunate,shorthand expression “chemical imbal-ance” to explain how antidepressants maywork. I have repeatedly pointed out that

this expression, even if intended to reducethe stigma associated with psychiatric ill-ness, is still misleading (Pies, 2011; Pies,2014a). I have also acknowledged that inthe 1990s, there was an overemphasis onthe role of serotonin in the etiology ofdepression (Pies, 2015b).

Unfortunately, the article by Drs.Lacasse and Leo (2015) in the October spe-cial issue of the Behavior Therapist (Deacon& McKay, 2015) misrepresents my views inthe matter of the so-called “chemicalimbalance theory” (CIT) and insinuatesthat I have acted in bad faith, owing toalleged “conflicts of interest.” These asper-sions seem based, in part, on the false claimthat I consider use of the chemical imbal-ance metaphor as merely “a little white lie”;and on the equally false claim that I was“paid to help [drug companies] promotetheir products.” Specifically:

• Lacasse and Leo (2015) mistakenlyimply that I either originated, orendorse, the phrase “little white lie” inreference to the CIT. In truth, I havenever applied that expression to, forexample, a clinician's telling a patient,“Your emotional problem is due simply

LETTER TO THE EDITOR

Response to Lacasse and Leo (2015)Ronald W. Pies, SUNY Upstate Medical University

P I E S

Winter • 2015 261

to a chemical imbalance.” I wouldregard such a statement as simplisticand reductionistic, and would nevershrug it off—as Lacasse and Leoimply—as “a little white lie.” Lacasseand Leo may have made an innocentmistake in attributing this expression tome, owing to two online versions of my“Nuances” article (2014a, 2014b).However, had they investigated care-fully, they would have seen that it wasjournalist Robert Whitaker who firstemployed the “little white lie” expres-sion in the context of the CIT (Levine,2014), and that my subsequent use ofthat phrase (Pies, 2014b) was in refer-ence to Whitaker’s comments in hisinterview with Bruce E. Levine. Unfor-tunately, in the Medscape version of my“Nuances” paper—which originallyappeared in Psychiatric Times (Pies,2014a)—I did not put Whitaker’sphrase in quotes, for which omission Itake responsibility. However, I couldeasily have cleared up any confusion onthis point, had Drs. Lacasse and Leo dis-cussed the matter with me, before writ-ing their article.

• Citing papers I co-authored in 2003 and2005—in which I disclosed havingreceived occasional speaking honorariafrom three pharmaceutical compa-nies—as well as my consulting workwith the medical communications com-pany Apothecom (2001–2006), Lacasseand Leo assert that “. . . he [Pies] waspaid to help [drug companies] promotetheir products at the time [their drug]advertisements were running” (p. 209).Lacasse and Leo reach this conclusionwithout any direct knowledge of formalarrangements or agreements I may havenegotiated in the years 2003–2005, or atany other time.

Let me be clear: never, in any lecture Idelivered that was underwritten by a phar-maceutical company, did I ever agree to“promote” a particular product; nor did Iever use slides or material provided by suchcompanies, or have any personal contactwith anyone representing the sponsoringcompany. I estimate that, in toto, I deliv-ered 5 to 6 lectures, over a 30-year period,that were underwritten to some extent bypharmaceutical companies—with which Ihad no ongoing financial relationships.

As for my part-time consulting rolewith Apothecom, all stipends came solelyfrom Apothecom and were paid to me onan ad hoc (hourly) basis. At no time did I

agree to “promote” any drug company’sproduct, nor was I induced or expected todo so by anyone at Apothecom. Of course,I am aware that “conflicts of interest” maysometimes arise inadvertently, even whenphysicians are not conscious of them, and Ihave written extensively on this issue (Pies,2013). Furthermore, by 2007, when Ibecame Editor-in-Chief of PsychiatricTimes (2007–2010), I no longer acceptedany lecture invitations (e.g., from varioushospitals) that were supported by pharma-ceutical companies.

As for Lacasse and Leo's (2015) allega-tion that I “. . . didn’t speak out on thechemical imbalance issue decades ago” (p.209)—for example, with an op-ed in theNew York Times—there is a straightfor-ward explanation for this. In my more than30 years in psychiatry, I never once heardany of my colleagues or teachers propounda simplistic “chemical imbalance theory” ofmental illness—or even of depression. Ibegan addressing this issue in 2011, as Ibecame increasingly aware of antipsychia-try bloggers using the “chemical imbal-ance” canard as a cudgel against psychiatry.

More substantively: Lacasse and Leo’s(2015) article ignores the critical distinc-tion between a hypothesis and a theory—thelatter being an integrated constellation ofvalidated hypotheses (Understanding Sci-ence, 2015). Specifically, they fail to distin-guish between the biogenic amine hypothe-sis of affective illness (which was indeedpropounded by some psychiatrists, ongood evidence) and a general, comprehen-sive theory that “mental illness is caused bya chemical imbalance”—which has neverbeen the position of any professional psy-chiatric organization, or of most academicpsychiatrists. Lacasse and Leo's confusionis highlighted in their quite unconvincingTable 2 (p. 211), which cites precisely 9 psy-chiatrists (out of over 36,000 in the U.S.!)who refer in some fashion to a “chemicalimbalance,” chiefly in the context of depres-sion; or with respect to an antidepressant’sputative mechanism of action—not as acausal theory of “mental illness” in general.

Moreover, Lacasse and Leo’s (2015)paper obscures the difference between aputative mechanism of action of a drug (e.g.,serotonin reuptake inhibition) and a causaltheory of mental illness (the focus of mywritings). To say that a drug “corrects achemical imbalance”—as, indeed, somepsychiatrists have stated—is not to claimthat the illness being treated is caused bythat imbalance. Many drugs work viamechanisms that are helpful for symptomsof a disease without addressing or revers-

ing the numerous (and often unknown)“causes” of that disease. For example, betablockers are used to treat some cardiacarrhythmias, but nobody infers from thisthat the arrhythmia is caused by a defi-ciency of beta-receptor blockade. (Nor, forthat matter, do cardiologists routinelyexplain to patients the mechanism ofaction of the medications they prescribe.)Of note: the most recent publicly availableinformation from the American Psychi-atric Association does not use the expres-sion “chemical imbalance” in discussingrisk factors for depression or the rationalefor antidepressant treatment (What IsDepression, 2015).

Finally: If there is anything resemblingan “official” psychiatric position on thecauses of mental disorders, it is the 1978statement from the American PsychiatricAssociation—which, unlike off-hand com-ments from one or another former APApresident, was approved by the APA Boardof Trustees, and is available online to thisday:

“Psychiatric disorders result from thecomplex interaction of physical, psycho-logical, and social factors and treatmentmay be directed toward any or all three ofthese areas.”

And this is precisely what most of my aca-demic colleagues and I have been teach-ing—and telling our patients—for the pastthree decades (Pies, 2015a).

ReferencesAmerican Psychiatric Assocation. (1979).

Position statement on active treatment.Retrieved from http://www.psychiatry.org/File%20Library/Learn/Archives/Position-1978-Active-Treatment.pdf

Compton, M. T., & Shim, R. S. (Eds.).(2015). The social determinants of mentalhealth. Washington, DC: American Psy-chiatric Publishing.

Deacon, B., & McKay, D. (Eds.). (2015).The biomedical model of psychologicalproblems [Special issue]. the BehaviorTherapist, 38(7).

Gold, P. W., Machado-Vieira, R., & Pavla-tou, M. (2015). Clinical and biochemicalmanifestations of depression: Relation tothe neurobiology of stress. Neural Plastic-ity, 2015. doi: 10.1155/2015/581976

Lacasse, J. R., & Leo, J. (2015). Antidepres-sants and the chemical imbalance theoryof depression: A reflection and update onthe discourse. the Behavior Therapist, 38,206-213.

R E S P O N S E T O T H E S P E C I A L I S S U E | B I O M E D I C A L M O D E L


Levine, B. E. (2014). Psychiatry nowadmits it's been wrong in big ways—Butcan it change? Retreived fromhttp://www.truth-out.org/news/item/22266-psychiatry-now-admits-its-been-wrong-in-big-ways-but-can-it-change-a-conversation-with-investigative-reporter-

Pies, R. (2011). Doctor, is my mood disor-der due to a chemical imbalance? PsychCentral. Retrieved from http://psych-central.com/blog/archives/2011/08/04/doctor-is-my-mood-disorder-due-to-a-chemical-imbalance/

Pies, R. (2013). Conflicts of interest: Con-cepts, conundrums, and course of action.Medscape, Nov. 11, 2013. http://www.medscape.com/viewarticle/813912

Pies, R. (2014a). Nuances, narratives, andthe “chemical imbalance” debate. Psychi-atric Times. April 11, 2014.http://www.psychiatrictimes.com/couch-crisis/nuances-narratives-chemical-imbalance-debate

Pies, R. (2014b). Nuances, narratives, andthe “chemical imbalance” debate. Med-scape. April 15, 2014. http://www.med-scape.com/viewarticle/823368_3

Pies, R. (2015a). Psychiatry’s solid center.Psychiatric Times, Oct. 7, 2015.http://www.psychiatrictimes.com/blogs/psychiatrys-solid-center

Pies, R (2015b). Serotonin: How psychiatrygot over its “high school crush.” Psychi-atric Times, Sept. 15, 2015.http://www.psychiatrictimes.com/blogs/couch-crisis/serotonin-how-psychiatry-got-over-its-high-school-crush#sthash.cB5eHgSR.dpuf

Schildkraut, J. J., & Kety, S. S. (1967). Bio-genic amines and emotion. Science, 156,21-37.

Understanding Science. (2015). Under-standing science: How science reallyworks. [Web page.] Retrieved fromhttp://undsci.berkeley.edu/article/how-scienceworks_19

What Is Depression. (2015). What isdepression? [Web page.] Retrieved fromhttp://www.psychiatry.org/patients-families/depression/what-is-depression

. . .

Correspondence to Ronald W. Pies, M.D.,SUNY Upstate Medical University; ClinicalProfessor of Psychiatry,Tufts UniversitySchool of Medicine; [email protected]

IN THEIR RECENT ARTICLE, Drs. Lacasseand Leo (2015) continue an important dis-cussion about the use of overly simplisticexplanations of antidepressant actions.They argue that drug companies have usedsuch explanations to market their drugs,and that psychiatrists have often been com-plicit—or at least silent—partners in thispromotional technique.

In one section of the article, they accuseme of making deceptive statements to mypatients about how antidepressants work. Ideny this accusation. In talking to patientsI simplify neurobiological concepts, usinga shorthand to describe, in a simplistic way,some common theories of mental illness. Ido this to enhance the placebo effect—which accounts for a significant portion ofthe overall effectiveness of antidepressants.Two of the most crucial components of theplacebo effect are fostering positive expec-tations of success and reinforcing the med-ical ritual of pill-taking (Kaptchuk et al.,2010; Leuchter, 2014). In order to augmentmy patients’ response to antidepressants, Iwill say something like, “This is a very effec-tive medication, you should take this pillevery morning, and you will begin to feelbetter within a couple of weeks.” If a patientasks me how the medication works, I willrespond with, “We’re not completely sure,but it has something to do with increasinglevels of neurotransmitters like serotoninor norepinephrine—basically, these pillsrebalance certain chemicals in the brain.”

There is nothing deceptive about suchstatements. While we don’t understandexactly what serotonin’s role is, we havesome educated hypotheses. A recentreview of serotonin and depression identi-fies 14 known serotonin receptor subtypes.When antidepressants bind to these recep-tors, a variety of chemical processes unfold,affecting levels of dopamine, norepineph-rine, acetylcholine, cortisol—and yes, sero-tonin. While it isn’t clear exactly how thesechemical cascades alleviate depression oranxiety, it is clear that effective antidepres-sants exert their actions via shifts in thebrain’s biochemical milieu—and that sero-tonin is one of the central players in thedrama (Kohler et al., 2015).

The authors, unfortunately, do notseem to be interested in scientific evidence.

In their role as the serotonin thoughtpolice, they brook no uncertainty: the sero-tonin theory is discredited, full stop. Tosupport this conviction, they refer to a tableentitled, “Evidence the Chemical Imbal-ance Theory of Depression Is Not Valid:Selected Quotations” (p. 210). But the tablepresents no “evidence” as we normallythink of the term. Instead, it is a list of 12statements made by various psychiatristsreflecting their personal opinions about thechemical imbalance theory. But justbecause smart people say something does-n’t make it true. If it did, then their Table 2,“Promotion of the Chemical ImbalanceTheory of Depression as Valid: SelectedQuotations” (p. 211) would be an effectiverefutation of their entire article.

Lost in their polemic is the fact that asmental health clinicians, we are fortunateto be able to offer very effective treat-ments—both psychotherapeutic and psy-chopharmacologic—for our patients.There is much we don’t understand, andwe can do better. But mean-spirited attackson colleagues are not going to help furtherthe field.

ReferencesKaptchuk, T. J., Friedlander, E., Kelley, J.

M., Sanchez, M. N., Kokkotou, E., Singer,J. P., . . . Lembo, A. J. (2010). Placeboswithout deception: A randomized con-trolled trial in irritable bowel syndrome.PLoS One, 5(12), e15591.

Kohler, S., Cierpinsky, K., Kronenberg, G.,& Adli, S. (2015). The serotonergicsystem in the neurobiology of depres-sion: Relevance for novel antidepres-sants. Journal of Psychopharmacology.doi: 10.1177/0269881115609072

Lacasse, J.R., & Leo, J. (2015). Antidepres-sants and the chemical imbalance theoryof depression: A reflection and update onthe discourse. the Behavior Therapist,38(7), 206-213.

Leuchter, A. F., Hunter, A. M., Tartter, M.,& Cook, I. A. (2014). Role of pill-taking,expectation and therapeutic alliance inthe placebo response in clinical trials formajor depression. British Journal of Psy-chiatry, 205(6), 443-449.

. . .

Correspondence to Daniel J. Carlat, M.D.,Tufts University School of Medicine;[email protected]


Response to Lacasse and Leo (2015)Daniel J. Carlat, Tufts University School of Medicine

C A R L A T

Winter • 2015 263

Response to Daniel Carlat (2015)In our recent article (Lacasse & Leo,

2015), we transcribed public statementsmade by Dr. Carlat on National PublicRadio (NPR). Dr. Carlat disclosed that heused content similar to the Zoloft market-ing campaign (Lacasse, 2005) to explainantidepressants to patients:

I’ll often say something like the wayZoloft works, is, it increases the level ofserotonin in your brain (or synapses,neurons), and, presumably, the reasonyou’re depressed or anxious is that youhave some sort of a deficiency. And I saythat [chuckles] not because I reallybelieve it . . . I think I say that becausepatients want to know something . . . .They certainly don’t want to know thata psychiatrist essentially has no ideahow these medications work. (Davies,2010)

Despite Dr. Carlat’s allegation, we arenot the serotonin thought police, ticketingoffenders that violate our sensibilities. But,we don’t believe we’re alone in thinking it’sobjectionable to tell patients somethingyou don’t believe yourself. To say thingslike this publicly and not expect criticismseems naïve. We are not cherry-pickinghere, as Dr. Carlat has a history of such dis-closures:

While it is true that most of our drugsaffect neurotransmitters in variousways, when psychiatrists start usingwhat I call neurobabble, beware,because we rarely know what we aretalking about. I fall into this habit withpatients all the time. When I find myselfusing phrases like “chemical imbalance”and “serotonin deficiency,” it is usuallybecause I’m trying to convince a reluc-tant patient to take a medication . . .(Carlat, 2010, p. 75; see pp. 74–83 for

published content similar to thatreported in the NPR interview)

We don’t think scientific truth is soflexible, and disagree with shaping it forpurposes convenient to the prescriber (e.g.,to get patients to take medication, or toreassure the patient of the prescriber’sexpert knowledge). Dr. Carlat also writesthat he boosts the placebo effect by tellingpatients that SSRIs are “a very effectivemedication” (Carlat, 2015; this issue, p.262). Fournier et al. (2010) demonstrateda Number-Needed-to-Treat (NNT) of 11for severely depressed patients. In otherwords, when prescribing to 11 severelydepressed patients, a prescriber wouldexpect 1 to have an impressive short-termresponse as compared to placebo. Giventhe existence of such data, we question theaccuracy of claiming that antidepressantsare “very effective” (see also Weitz et al.,2015).

Response to Ronald Pies (2015)On the “Little White Lie” of ChemicalImbalance

In his reply, Dr. Pies (2015; this issue)states that he does not endorse calling thechemical imbalance a “little white lie,” andthat he was referencing Mr. RobertWhitaker when he used this phrase. Wetake his word on this, appreciate that heacknowledges his editorial error, and apol-

ogize for the confusion. We are glad thatwe and Dr. Pies have this opportunity tocorrect the record.1 We note that a correc-tion has been made to Dr. Pies’ originalarticle as of November 4, 2015 (Pies, 2014).

On Promotion of Psychiatric DrugsLike many, we believe that academic

psychiatrists have been too closely alignedwith the pharmaceutical companies (e.g.,Healy, 2004). In our article, we hypothe-sized, as we had before (Lacasse & Leo,2009), that the flow of money from drugcompanies to academic psychiatry mightbe partially responsible for the resoundingsilence in academia regarding misleadingadvertising of psychiatric drugs. Dr. Pieshad himself argued that pharmaceuticalcompanies were responsible for spreadingthe chemical imbalance metaphor. Whilewe agreed that this was part of the problem(Lacasse & Leo, 2005), we saw some ironyin the fact that he had received fundingfrom GlaxoSmithKline, among the worstoffenders in our opinion when it came tomisleading consumer advertising. Wenever accused Dr. Pies of acting in badfaith, and in fact wrote, “We want to beclear that we are not accusing Dr. Pies ofanything” and that entanglements withdrug companies aren’t “uncommonamong academic psychiatrists, and somewould say it was par for the course in the2000s” (Lacasse & Leo, 2015, p. 209). How-ever, Dr. Pies strongly objects to our asser-tion that he has been involved in the pro-motion of psychiatric drugs, and so we willreluctantly respond.

How Psychiatric Drugs Are PromotedAs background, it is useful to under-

stand the strategies that pharmaceuticalcompanies use to promote2 their products.They often contract with “medical com-munications companies,” which specializein “publication planning” and employmedical writers who contribute to (or evenauthor or co-author) peer-reviewed arti-cles (Lacasse & Leo, 2010), usually withacademics listed as authors on the byline


Response to Daniel Carlat (2015)and Ronald Pies (2015)Jeffrey R. Lacasse, Florida State University

Jonathan Leo, Lincoln Memorial University–deBusk College ofOsteopathic Medicine

1In his 2014 article, Dr. Pies begins a paragraph by citing an interview of Mr. Robert Whitaker(Levine, 2014; Pies, 2014). Dr. Pies then writes about the “antipsychiatry movement.” In thesesentences there are no quotations and no citations; they consist of Dr. Pies’ own interpretations.He mentions chemical imbalance, writing that “by promoting this little white lie…” Mr.Whitaker had used quotation marks around the phrase as editorial comment, but Dr. Pies didnot. 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-tion from Dr. Pies in a footnote, commenting on this exact issue (Lacasse & Leo, 2015, p. 209). Acorrection to the article (Pies, 2014) was made in November of 2015, after our article was pub-lished. Rather than clarifying where the phrase “little white lie” came from, Dr. Pies removed itand replaced it with “simplistic formulation.” Interestingly, Mr. Whitaker did not characterizechemical imbalance as “simplistic” (Levine, 2014).


(Sismondo, 2009; Sismondo & Doucet,2010). Unrestricted educational grants areanother strategy used by pharmaceuticalcompanies, as they are “. . . a well-estab-lished tool that all of the major pharmaceu-tical manufacturers use to disseminateinformation to the medical community. . . .The off-label promotion risk of educationalgrants appears to pose the greatest threat tothe Federal health care programs and ben-eficiaries, but it is also the most difficult todemonstrate conclusively”3 (U.S. SenateCommittee on Finance, 2007). Nonethe-less, the legal complaint against Glaxo-SmithKline for illegal marketing of drugslike Paxil and Lamictal (which was eventu-ally settled for 3 billion dollars; Departmentof Justice, 2012) described the following:

GSK’s [GlaxoSmithKline’s] extremelyaggressive off-label marketing cam-paigns for Lamictal included spendinglarge sums of money in the form ofunrestricted grants, membership onadvisory boards and speaker’s fees onphysicians and researchers who servedas “national thought leaders.” (UnitedStates of America v. GlaxoSmithKline,2012)

Certainly many professors believe theyare being hired to share their expert opin-ion, but in the eyes of pharmaceutical andmedical communications companies, aca-demics are clearly being paid because theiropinions are helpful in the promotion ofthe drug company’s product.4 At the risk ofstating the obvious, from the companies’point of view, it would make no sense topay psychiatrists or medical writers if theydidn’t have positive things to say about theproduct. From their point of view, the ideal

academic would be someone who believesthat grants, payments, or the assistance ofmedical writers have no effect on theirobjectivity. In fact, academics receivingfunding from drug companies or proxiesmay be genuinely unaware that they havebeen retained because their opinions havepromotional value (e.g., Carlat, 2007). Wedo not believe that academics agree to justsay anything the companies want in returnfor compensation, and we never assertedthat Dr. Pies was a “hired gun.” We sharethe views of Dr. David Healy (2012), whoargues that pharmaceutical companies seekout academics who already share theirviews.

Our ClarificationFirst of all, our statements were not

based on any direct or firsthand knowledgeof any verbal or written agreement that Dr.Pies had with Apothecom, or any othercorporate entity. We were trying to bebrief, and so we wrote that Dr. Pies “fails tomention that he was paid to help them[drug companies] promote their products”(Lacasse & Leo, 2015, p. 209). In retrospect,we could have written more clearly andspecifically, and we therefore correct thissection to read as follows:

Dr. Pies blames the drug companies forrunning misleading advertisements aboutchemical imbalance, belatedly admits heshould have done something sooner, butfails to mention his involvement with thepharmaceutical industry. In 2005, he dis-closed that “he has consulted for an inde-pendent medical education company thatinvolves work with pharmaceutical com-pany clients” (Pies & Rogers, 2005).5 As of2003, Dr. Pies disclosed that he was a recip-ient of “ad hoc stipends from Abbott,

Jannsen, GlaxosmithKline, and other phar-maceutical or related corporate entities”(Chaudron & Pies, 2003, p. 1284). In thissame 2003 article, Dr. Pies disclosed that hewas a consultant for Apothecom (Chau-dron & Pies, 2003), a medical communica-tions agency listed in the Top-100 agenciesby Medical Marketing and Media (Frank,2015). The Apothecom website boasts thatthey are a “communications powerhouse”employing “130 scientific storytellers” andthat they do “scientific branding . . . publi-cations planning, delivery and maximizing. . .” (Apothecom.com, 2015). Dr. Piesreports working with Apothecom from2001–2006 (Pies, 2015). As of 2003,Apothecom listed the pharmaceuticalcompanies Abbott, Sepracor, and Glaxo-smithKline among their clients (Lieber-man, 2003).

From 2002–2006, Dr. Pies was authoror co-author of articles funded throughunrestricted educational grants from Glaxo-SmithKline (makers of the anticonvulsantdrug Lamictal). These include an articleentitled “The 'Softer' End of the BipolarSpectrum” (Pies, 2002a); a 2002 article oncombining lithium with anticonvulsantssuch as Lamictal in bipolar disorder (Pies,2002b); a review article on “Matching theBipolar Patient and the Mood Stabilizer”(Gelenberg & Pies, 2003); a 2003 article onpostpartum psychosis and bipolar disorderstating that Lamictal “. . . also not FDA-approved for treatment of bipolar disorder,does appear especially useful for bipolardepression” (Chaudron & Pies, 2003, p.1289);6 a review article focused on treat-ment of bipolar disorder with co-occurringsubstance use (Albenese & Pies, 2004); anda 2006 article recommending Lamictal foruse in maintenance treatment of bipolardisorder (Marken & Pies, 2006). Another2006 article funded by GlaxoSmithKlinestated that “lamotrigine [Lamictal] mayalso have benefits in borderline personalitydisorder” (MacKinnon & Pies, 2006, p. 8),with the co-authors disclosing that “Theauthors of this paper do not have any com-mercial associations that might pose a con-flict of interest in connection with thismanuscript” (MacKinnon & Pies, 2006, p.1). Dr. Pies was also co-author of a reviewarticle on treatments for insomnia whichhighlights the potential benefits of Lunesta,and acknowledges the assistance of Sepra-cor, Inc. (makers of Lunesta) in the prepa-ration of the manuscript (Winkelman &Pies, 2005);7 and co-author of a 2007 arti-cle on insomnia in which the authorsacknowledge “that they received compen-sation from Sepracor for services they pro-

2The Oxford Dictionary defines promote as “...Further the progress of (something, especially acause, venture or aim); support or actively encourage... Give publicity to (a product, organization,or venture) so as to increase sales or public awareness...”. The word “promotion” by itself doesnot imply that the information is biased, inaccurate or deceptive, nor is it intrinsically negative.Products can be honestly and enthusiastically promoted. This point may have been overlooked bysome readers of our original article. Sismondo (2009) describes a balance between marketing andscience among publication planners.3One reason that it so difficult to demonstrate this conclusively, as the Senate notes, is because inmany cases the money trail is complicated and difficult to sort out from the outside.4Like our original article and the rest of this response, this paragraph reports our academic opin-ion on these issues.5This is seemingly Apothecom, but Dr. Pies did not disclose the name of the company.6Ghaemi, Shirzadi, and Filkowski (2008) examined GlaxoSmithKline’s unpublished negative stud-ies and wrote: “[Lamictal] has very limited, if any, efficacy in acute bipolar depression and rapid-cycling bipolar disorder, areas in which practicing clinicians, as well as some academic leaders,have supported its use.”7In an Op-Ed in the New York Times, Dr. Daniel Carlat critiqued an arguably similar article as aform of pharmaceutical company marketing (Carlat, 2006).



Winter • 2015 265

vided in support of the development of thismanuscript” (Roth, Roehers, & Pies, 2007,p. 77). Several of the above-listed articlesacknowledge editorial assistance and/orcontent contribution from medical writerswithout listing their company affiliation orwho paid them for their work; the onlineresume of one such medical writer listsApothecom as her employer at the time.Dr. Pies wrote that his relationship withApothecom took place from 2001–2006(Pies, 2015). In 7 of the 8 journal publica-tions discussed above, Dr. Pies does notdisclose a relationship with Apothecom.

DiscussionWhile we are pleased to make these

clarifications, we think the primary issueremains the use of the chemical imbalancemetaphor in clinical interactions with vul-nerable patients. We find Dr. Pies’ argu-ments unconvincing, and it is obvious to usthat the chemical imbalance theory wasindeed embraced by the field of psychiatry(Whitaker, 2015), and that the explanationis still used by prescribers to this day. Wehave wondered what has motivated Dr.Pies’ shifting positions and arguments onthis topic (Lacasse & Leo, 2015; Whitaker,2015), and in his reply, we think he gave ananswer. Dr. Pies writes, “I began address-ing this issue in 2011, as I became increas-ingly aware of antipsychiatry bloggersusing the 'chemical imbalance' canard as acudgel against psychiatry” (Pies, 2015, thisissue, p. 261). We think this is useful con-text to guide interpretation of his argu-ments. Dr. Pies is apparently defending hisguild against outside attack (Whitaker,2015; Whitaker & Cosgrove, 2015). Read asa sustained, political defense of his profes-sion, we think his writings on chemicalimbalance make perfect sense.

We are not part of this guild, so we havea different point of view. We think theseissues are deeply important, not becausepsychiatry is under attack, but because webelieve many depressed and anxiouspatients have been hurt by being told thatthey have a chemical imbalance in theirbrain that is corrected by psychiatric med-ication. We think calling this “misleading”is an understatement—and that learningnow that chemical imbalance is only ametaphor (Lacasse & Leo, 2006) could wellbe traumatic. This is true both for the pre-scribers who were taught to use thismetaphor, as well as for the patients whoheard it from their physicians and believedit to be a scientific fact. As anyone who hasdealt with trauma knows, the first step is toacknowledge what happened. Insisting that

it never occurred, or was less severe thanperceived, or was unsanctioned by author-ities, will inevitably cause negative reac-tions—especially so when these claims arenot quite true.

We think it is in the best interests of thepsychiatric profession to look closely athow the chemical imbalance metaphor hasbeen used over the last 25 years. This is noeasy task (Tavris & Aronson, 2008). Itrequires putting ego aside, listening care-fully rather then lecturing, and a willing-ness to be open-minded and nondefensive.Rather than obfuscating the issue, ordemonizing those delivering the bad newsas “antipsychiatry,” the profession willeventually need to admit that patients weremisinformed and harm was done. Oncethis step is taken, perhaps psychiatry canrecapture the public’s trust and move for-ward.

ReferencesAlbanese, M. J., & Pies, R. (2004). The

bipolar patient with comorbid substanceuse disorder. CNS Drugs, 18(9), 585-596.

Carlat, D. (2006). Generic smear campaign.New York Times. http://www.nytimes.com/2006/05/09/opinion/09carlat.html?pagewanted=print&_r=0

Carlat, D.J. (2007, November 25). Dr. DrugRep. New York Times. http://www.nytimes.com/2007/11/25/magazine/25memoir-t.html?pagewanted=all

Carlat, D.J. (2010). Unhinged: The troublewith psychiatry – A doctor’s revelationsabout a profession in crisis. New York:Free Press.

Carlat, D. (2015). Response to Lacasse andLeo. the Behavior Therapist, 38, 262.

Chaudron, L. H., & Pies, R. W. (2003). Therelationship between postpartum psy-chosis and bipolar disorder: A review.The Journal of Clinical Psychiatry, 64(11),1284-1292.

Davies, D. (2010). A psychiatrist’s prescrip-tion for his profession. [Interview].Retrieved from www.wbur.org/npr/128107547

Department of Justice. (2012). Settlementagreement with GlaxoSmithKline.http://www.justice.gov/sites/default/files/opa/legacy/2012/07/02/plea-ex-b.pdf

Fournier, J. C., DeRubeis, R. J., Hollon,S.D., Dimidjian, S., Amsterdam, J. D.,Shelton, R. C., & Fawcett, J. (2010). Anti-depressant drug effects and depressionseverity: A patient-level meta-analysis.JAMA, 303, 47-53.

Frank, J. (2015). Top-100 agencies 2015:ApotheCom. Medical Marketing andMedia. http://www.mmm-online.com/top-100-agencies/top-100-agencies-

2015-the-apothecom-group/arti-cle/422897/

Gelenberg, A. J., & Pies, R. (2003). Match-ing the bipolar patient and the mood sta-bilizer. Annals of Clinical Psychiatry,15(3-4), 203.

Ghaemi, S.N., Shirzadi, A.A., & Filkowski,M. (2008). Publication bias and the phar-maceutical industry: The case of lamotrig-ine in bipolar disorder. Medscape.http://www.medscape.com/viewarticle/579046

Healy, D. (2004). Let them eat Prozac: Theunhealthy relationship between the phar-maceutical industry and depression. NewYork: New York University.

Healy, D. (2012). Pharmageddon. Berke-ley: University of California.

Hickey, P. (2014). Psychiatry DID promotethe chemical imbalance theory.http://www.madinamerica.com/2014/06/psychiatry-promote-chemical-imbal-ance-theory/

Lacasse, J.R. (2005). Consumer advertisingof psychiatric medications biases thepublic against non-pharmacologicaltreatment. Ethical Human Psychologyand Psychiatry, 7(3), 175-179.

Lacasse, J.R., & Leo, J. (2005). Serotoninand depression: A disconnect betweenthe advertisements and the scientific lit-erature. PLoS Medicine, 2(12), 101-106.

Lacasse, J.R., & Leo, J. (2006). Question-able advertising of psychotropic medica-tions and disease mongering. PLoS Medi-cine, 3(7), 1192.

Lacasse, J.R., & Leo, J. (2009). Consumeradvertisements for psychostimulants: Along record of misleading promotion.Psychiatric Times, 26(2). http://www.psychiatrictimes.com/articles/consumer-advertisements-psychostimulants-united-states

Lacasse, J.R., & Leo, J. (2010). Ghostwrit-ing at elite academic medical centers inthe United States. PLoS Medicine.doi:10.1371/journal.pmed.1000230

Lacasse, J.R., & Leo, J. (2015). Antidepres-sants and the chemical imbalance theoryof depression: A reflection and update onthe discourse. the Behavior Therapist,38(7), 206-213.

Levine, B. (2014). Psychiatry now admitsit’s been wrong in big ways—But can itchange? Truthout. http://www.truth-out.org/news/item/22266-psychiatry-now-admits-its-been-wrong-in-big-ways-but-can-it-change

Lieberman, M. (2003, August 1). Medicaleducation review: MM&M’s annualsurvey of medical education companiesfinds a bullish business outlook, with anoverwhelming majority of companies pre-dicting increases in worldwide businessvolume [Medical education survey/direc-


tory]. Medical Marketing and Media.https://web.archive.org/web/20151107180330/http://www.highbeam.com/doc/1G1-106941989.html

MacKinnon, D. F., & Pies, R. (2006).Affective instability as rapid cycling: The-oretical and clinical implications for bor-derline personality and bipolar spectrumdisorders. Bipolar Disorders, 8(1), 1-14.

Marken, P. A., & Pies, R. W. (2006).Emerging treatments for bipolar disor-der: Safety and adverse effect profiles.Annals of Pharmacotherapy, 40(2), 276-285

Pies, R. (2002a). The “softer” end of thebipolar spectrum. Journal of PsychiatricPractice, 8(4), 189-195.

Pies, R. (2002b). Combining lithium andanticonvulsants in bipolar disorder: Areview. Annals of Clinical Psychiatry,14(4), 223-232.

Pies, R. (2006). Prenatal antidepressantuse: Time for a pregnant pause? Psychi-atric Times. http://www.psychiatric-times.com/depression/prenatal-antide-pressant-use-time-pregnant-pause/page/0/1

Pies, R.W. (2011). Doctor, is my mood dis-order due to a chemical imbalance?http://psychcentral.com/blog/archives/2011/08/04/doctor-is-my-mood-disorder-due-to-a-chemical-imbalance/on August13, 2015

Pies, R.W. (2014). Nuances, narratives,and the “Chemical Imbalance” debate.

Medscape Psychiatry. http://www.med-scape.com/viewarticle/823368

Pies, R. (2015). Response to Lacasse andLeo (2015). the Behavior Therapist, 38,260-262.

Pies, R., & Rogers, D. (2005). The recogni-tion and treatment of depression: Areview for the primary care clinician.Medscape. http://www.medscape.org/viewprogram/4572 [‘Faculty and Disclo-sures”]

Roth, T., Roehrs, T., & Pies, R. (2007).Insomnia: Pathophysiology and implica-tions for treatment. Sleep MedicineReviews, 11(1), 71-79.

Sismondo, S. (2009). Ghosts in themachine: Publication planning in themedical sciences. Social Studies of Sci-ence, 39(2), 171-198.

Sismondo, S., & Doucet, M. (2010). Publi-cation ethics and the ghost managementof medical publication. Bioethics, 24(6),273-283.

Tavris, C., & Aronson, E. (2008). Mistakeswere made (but not by me): Why we jus-tify foolish beliefs, bad decisions, andhurtful acts. Orlando, FL: Harcourt.

U.S. Senate Committee on Finance.(2007). Use of educational grants by phar-maceutical manufacturers. http://www.finance.senate.gov/newsroom/chair-man/download/?id=9789677a-58eb-42bd-bba1-142d08083a7e

United States of America v. SmithKlineBeecham/GlaxoSmithKline. (2012).http://www.quitam-lawyer.com/sites/

quitam-lawyer.com/files/02.03.12%20-%20GSK%20-%207th%20Amended%20Complaint.pdf

Weitz, E. S., Hollon, S. D., Twisk, J., vanStraten, A., Huibers, M. J., David, D., ...Cuijpers, P. (2015). Baseline depressionseverity as moderator of depression out-comes between cognitive behavioraltherapy vs pharmacotherapy: An individ-ual patient data meta-analysis. JAMAPsychiatry, 72,1102-1109. doi:10.1001/jamapsychiatry.2015.1516

Whitaker, R. (2015). Ronald Pies doublesdown (And why we should care).Retrieved November 1, 2015, fromhttp://www.madinamerica.com/2015/09/ronald-pies-doubles-down-and-why-we-should-care/

Whitaker, R., & Cosgrove, L. (2015). Psy-chiatry under the influence: Institutionalcorruption, social injury, and prescrip-tions for reform. New York: Palgrave-Macmillan.

Winkelman, J., & Pies, R. (2005). Currentpatterns and future directions in thetreatment of insomnia. Annals of ClinicalPsychiatry, 17(1), 31-40.

. . .

Correspondence to Jeffrey R. Lacasse,Ph.D., Florida State University College ofSocial Work; [email protected]

■ CLASSIFIED

FELLOWSHIPS IN ADVANCEDCOGNITIVE THERAPY FOR SCHIZ-OPHRENIA WITH AARON T. BECK.We offer an exciting opportunity forpostdoctoral applicants in the Aaron T.Beck Psychopathology Research Centerat the University of Pennsylvania.Specifically, our mission is to developprofessionals who will become leaders inthe field of psychological approachesthat promote recovery for individualswith schizophrenia. Under the directionof Aaron T. Beck, M.D., our programincludes basic research in schizophrenia,clinical trials of innovative treatmentsfor the disorder, and dissemination andimplementation of these treatment pro-tocols into community mental healthcenters and psychiatric hospitals. Wehave been recognized for our cuttingedge work in this field. For more infor-mation, see http://aaronbeckcenter.org

Applicants who have earned an M.D.,Ph.D., Psy.D., or equivalent in psycholo-gy or other related field and have hadprevious training in cognitive therapy,severe mental illness, or recovery- ori-ented services are encouraged to apply.Bilingual candidates are especiallyencouraged to apply.

Please send a curriculum vita with acover letter and two letters of recom-mendation via email to Aaron T. Beck,M.D., at [email protected].

The University of Pennsylvania is anEqual Opportunity/Affirmative ActionEmployer. Applications will be accepteduntil January 1, 2016.

Anne Marie Albano

P. Michael Apolito

John Grebe

Lisa Hale

B. Linnea Lindholm

Matthew Pearson

Tom Olson

David Roll

Ei leen Senior

On behalf of ABCT, President JonathanS. Abramowitz warmly thanks all whohave generously supported our mission

with a voluntary personaldonation in 2015.

Voluntary Contributors



leo antidepressantsandthechemicalimbalance ... · levine, 2014). for instance, alan frazer,...

Documents