What the advertisements said, and what the literature said

Nobody reading this was foolish for believing it. The sentence was everywhere, it was usually said kindly, and it came from sources people had every reason to trust.

Significant findings

In 2005 Jeffrey Lacasse and Jonathan Leo published an essay in PLoS Medicine that set the advertisements next to the literature. A Pfizer television advertisement for Zoloft, March 2004: "While the cause is unknown, depression may be related to an imbalance of natural chemicals between nerve cells in the brain. Prescription Zoloft works to correct this imbalance." A GlaxoSmithKline advertisement for Paxil in Newsweek, October 2001, said the drug "works to correct the chemical imbalance believed to cause the disorder." An Eli Lilly advertisement for Prozac in People, January 1998: "When you're clinically depressed, one thing that can happen is the level of serotonin (a chemical in your body) may drop."

Against that, their reading of the science: "there is no scientifically established ideal 'chemical balance' of serotonin, let alone an identifiable pathological imbalance", and "to our knowledge, there is not a single peer-reviewed article that can be accurately cited to directly support claims of serotonin deficiency in any mental disorder". They also record something the argument usually leaves out. The approved prescribing information for paroxetine made no such claim. The label and the advertisement did not say the same thing.

Regulators mostly did not intervene. The essay counts ten warning letters sent by the FDA to antidepressant manufacturers since 1997, and says none of them cited this claim. The exception it records is Irish: it reports that the Irish Medical Board banned GlaxoSmithKline from claiming that paroxetine corrects a chemical imbalance, even in patient information leaflets.

Whether the profession itself taught this is genuinely disputed, and this trail does not settle it. The psychiatrist Ronald Pies wrote in 2011 that the chemical imbalance "was always a kind of urban legend - never a theory seriously propounded by well-informed psychiatrists" (Psychiatric Times, 11 July 2011 - a trade publication, not peer-reviewed). In 2014 he added that "some psychiatrists did hold a purely biocentric view" and "some undoubtedly used the expression". Against him, Ang, Horowitz and Moncrieff examined 30 highly cited reviews of the causes of depression, 30 highly cited serotonin papers and a set of influential textbooks from 1990 to 2010, and reported that most reviews supported the theory and "all textbooks supported the theory, at least in some sections" (doi:10.1016/j.ssmmh.2022.100098). Pies and a co-author replied in the same journal (doi:10.1016/j.ssmmh.2022.100133).

Worth asking

Where the sentence reached people is measurable. In a 2007 survey of 262 US undergraduates, 92% had previously seen or heard depression described as a chemical imbalance - and of those who said where, 46% named a physician or other medical professional. If you were told it, the question worth carrying is not whether you were misled. It is the plain one: what would my prescriber say today about why this medication, for me?