“Depression has acted as the template for the creeping medicalization of a widening array of life problems,” contends Joanna Moncrieff in her startling and insightful new book, Chemically Imbalanced: The Making and Unmaking of the Serotonin Myth, published today in the United Kingdom by Flint Books at The History Press.
By carefully unpicking what sociologist Nikolas Rose called the “psychiatric re-shaping of discontent,” a transformation that began in the 1950s but accelerated in the 1970s and late 1980s, Moncrieff shows how the framing of depression and its treatment evolved from a “drug-centered” to a “disease-centered” model, with significant implications for how we think about the condition, even before we set about treating it.
From the 1950s on, the “drug-centered” focus took a precautionary line on foreign chemical substances. It highlighted their psychoactive, brain-modifying properties, including the risk of adverse effects and longer-term harms. The second, “disease-centered” model helped psychiatrists and other prescribers overcome that concern by cementing the idea that depression is a biological phenomenon, and antidepressants are allegedly the most effective way to target its underlying mechanisms.
That is where the serotonin hypothesis of depression comes in, as the central platform for a broader “chemical imbalance” theory of depression, anxiety, and mood disorders. As Moncrieff puts it, the serotonin hypothesis—the idea that low serotonin is the predominant cause of depression—“forms the principal justification for the use of antidepressants.”
Without that justification, much of the pressure and urgency to prescribe—to correct a biological anomaly or neurochemical deficiency—vanishes.
But as we learn from Moncrieff’s riveting account of how she briefly became its victim, the construct itself doesn’t thereby disappear. Discredited theories aren’t simply removed from circulation, as if by fiat or fast-established consensus. Especially if they have been publicized over many years by drug makers and influential figures, they can quickly assume new life. Indeed, the book confirms that if enough trust is placed in the construct, even its most discredited parts can be revived on merely the promise of future-confirming data.
International news, then a campaign to discredit
When Moncrieff led a systematic review of meta-studies on the relationship between serotonin and depression, her team—involving five other top UK and European specialists—determined from all relevant published studies that “there is no evidence of a connection between reduced serotonin levels of activity and depression.”
They found, as well, that there is “little evidence that antidepressants have substantially greater effects in people with more severe depression.” And, even more, they found that “well-conducted studies indicate that differences between the brains of depressed patients and healthy individuals are ‘remarkably small’ and that ‘similarity’ predominates.”
Professor of psychiatry at University College London and author of The Myth of the Chemical Cure, among other books and studies, Moncrieff began work as a medical researcher, then as a junior doctor and psychiatrist in the UK’s National Health Service when a series of rolling scandals over barbiturates, then benzodiazepines, followed by opioids fostered deep-seated skepticism about drug-centered treatment, including its adverse and potential long-term harms.
Published in Molecular Psychiatry and read by more than one million, the review attracted international coverage, sent shockwaves through academic psychiatry, and caused something of a furor over SSRI and SNRI antidepressants. With almost 20 percent of the adult UK population currently taking antidepressants for depression, questions quickly intensified over the risk of overprescribing and whether the public had been misled over their efficacy and mechanism of function. (Some of the controversy was reported here.)
The majority of clinics and institutes continued to promote the chemical imbalance hypothesis without regard. Several academic psychiatrists acknowledged that the chemical “metaphor” had, to them, become acceptable “shorthand” for drug effects they still could not explain but believed future studies would.
But the problem for those seeking to discredit Moncrieff’s systematic review—including, we learn, largely because of its findings—is that she brings receipts every time. Example after example of misreported or overinflated data makes it near-impossible to dispute her contention that the “scientific literature is … misleading and frequently overstates its findings.”
Whereas re-examination of the STAR-D clinical trial data revealed that the efficacy of SSRIs had been significantly overinflated, in the notorious “Study 329” trial, the drug-maker sponsoring the research was later found, in Moncrieff’s words, to have “fiddled the data, replacing the originally designated primary outcome measure, which showed a negative result, with one that was positive.” With outsized chutzpah, they went on to market the drug producing the negative data (paroxetine) as showing “REMARKABLE safety and efficacy.” It had in fact shown nothing of the kind.
Moncrieff asks with disarming bluntness: “What are we to make of the fact that antidepressants, among the most commonly used drugs of modern times, have not been convincingly shown to be beneficial, either in the short term or the long term? How is it possible that doctors, policy-makers, the media, and the public have carried on as if they do?”
The fiction of the chemical imbalance
One conclusion drawn from a now almost-impassable gulf between scientific evidence and popular understanding of antidepressants is that the “chemical imbalance” metaphor has served several interests, one of them to delay professional reckoning over the evidence itself.
“Many leading psychiatrists were perfectly happy for people to go on believing in the fiction of the chemical imbalance,” Moncrieff observes; they “not only failed to stop the industry from spreading the myth about the chemical imbalance, frequently they joined in, because despite knowing the theory was unproven, they desperately wanted to believe it themselves.”
That would account for some of the hostility to Moncrieff’s and her team’s findings, including that discrediting the theory supposedly wouldn’t matter if the drugs still “work.” But, obviously, it does matter that patients receive reliable, accurate information about antidepressants, including so they can make informed decisions about whether to take them.
It also matters if a psychoactive compound with well-known adverse effects generates an “amplified” placebo response only marginally superior to that of a sugar pill. As Harvard scholar Irving Kirsch underlined in 2011, that would strongly indicate that the “antidepressant” effect wasn’t chiefly pharmacological but drawn more from hope or expectation of the depression lifting.
Regarding our “disease-centered” model of depression, Chemically Imbalanced argues that “the process of medicalization only makes things worse. It gives people false hope and leads to the over-prescription of potentially harmful drugs that, at best, offer ways to stifle uncomfortable feelings. We have to find better ways to help people.”
Better ways, according to Moncrieff, would include framing the treatment of depression as “first and foremost about helping people to address the problems in their lives.” Whether through problem-solving therapy or psychotherapy; changes in sleep routine, diet, and exercise; or major life changes aimed at tackling long-standing problems, those using treatments that bypass psychiatric drugs describe recovery from depression as involving “changing their circumstances but also changing fundamental aspects of themselves—what they valued and how they lived.”
Authoritative and well-researched, Chemically Imbalanced documents the overinflation of antidepressant efficacy, where the false scientific information repeated is altogether misleading.
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