On November 8, 2022, the New York Times published “Antidepressants Don’t Work the Way Many People Think,” noting the following: “A paper published earlier this year made headlines for presenting several decades’ worth of evidence that people with depression don’t have less serotonin than people who are not depressed.” The “paper” referred to is a comprehensive review of the research, published in Molecular Psychiatry in July 2022, lead-authored by psychiatrist Joanna Moncrieff, co-chairperson of the Critical Psychiatry Network, who concluded that there is no evidence for the serotonin imbalance theory of depression.
The Times article uncritically reported the responses of leading figures in psychiatry to Moncrieff’s review. They asserted: (1) her conclusions are not news, as the serotonin imbalance theory of depression is an “old theory” that has long been discarded by psychiatry; and (2) it does not matter that antidepressants do not work to correct a chemical imbalance because antidepressants are very effective.
These responses should have resulted in at least two questions for serious journalists and their editors: (1) If the serotonin imbalance theory of depression—an idea which convinced many people to take selective serotonin reuptake inhibitors (SSRIs) such as Prozac, Zoloft, and Celexa so as to correct this imbalance—has long been discarded by psychiatry, why has Moncrieff’s findings, as the Times put it, “made headlines”? (2) Given that antidepressants lack a neurobiological rationale of correcting a chemical imbalance, what is the evidence that antidepressants are scientifically effective (i.e., more effective than a placebo, and more effective than the simple passage of time)?
With regard to the issue of why so many people were unaware that psychiatry has long known that the serotonin imbalance theory of depression was untrue, the Times did not investigate whether psychiatry authorities had continued asserting this theory after research had disproven it. Others have investigated this issue (more later on this).
With regard to the second issue of antidepressant effectiveness, the Times article included a section titled “What do we know about antidepressant effectiveness?” While noting the significance of the placebo effect in outcome studies, the Times focused primarily on one study, the “Sequenced Treatment Alternatives to Relieve Depression” (STAR*D), and the Times uncritically accepted its sources’ assertion that STAR*D had clearly proven the effectiveness of antidepressants. The Times did not mention that the STAR*D remission rate had been criticized even within the psychiatry establishment as greatly inflated, and that other researchers have concluded that an analysis of the STAR*D data points to “real-world” ineffectiveness of antidepressants.
The STAR*D Study
Funded by the National Institute of Mental Health (NIMH) in the early 2000s, STAR*D results were reported on in 2006. Its goal was to assess antidepressant effectiveness in the “real world”—where depressed patients who don’t remit with one antidepressant are prescribed another. Thus, there were four treatment stages in STAR*D, each lasting three months. In the first stage, all depressed patients received the SSRI antidepressant Celexa, and these Celexa-treated patients who failed to have remission of depression symptoms were then, in a second three-month stage, assigned to several other treatment modes, including the substitution of Celexa with other antidepressants. Depressed patients who continued to be non-remitters after these first two stages were encouraged to enter a third stage which included other types of antidepressants; and for those who continued to be non-remitters; there was a fourth stage of other antidepressants.
The Times, uncritically repeating the STAR*D authors’ claim, reported that “nearly 70 percent of people had become symptom-free by the fourth antidepressant.” Unreported by the Times was this glaring conflict of interest: In the 2006 STAR*D report, at its end in small print, are the details of the financial relationships of the two lead STAR*D investigators (psychiatrists A. John Rush and Madhukar H. Trivedi) with multiple pharmaceutical companies, including the manufacturers of several of the antidepressants used in STAR*D, such as Forest Pharmaceuticals (Celexa), Wyeth-Ayerst Laboratories (Effexor), GlaxoSmithKline (Wellbutrin), and Pfizer (Zoloft). Also detailed were the financial relationships of the several other STAR*D investigators with drug companies.
The Times article did report one obvious problem with STAR*D, “One critique of the STAR*D trial is that it didn’t compare the medications against a placebo.” This failure to include a control group is only the tip of a large iceberg of STAR*D methodological problems, obfuscations, and deceptions that went unreported by the Times.
Before examining the STAR*D study issues that render its “nearly 70 percent” (more precisely, 67 percent) remission rate statistic meaningless, it is important to keep in mind that even if that 67 percent rate was valid, such a year-long cumulative remission rate is not evidence of antidepressant effectiveness. Unreported by the Times was another 2006 NIMH-funded study, “The Naturalistic Course of Major Depression in the Absence of Somatic Therapy,” that found 85 percent of the non-medicated patients recovered within a year, and the authors concluded: “If as many as 85% of depressed individuals who go without somatic treatments [which include antidepressants] spontaneously recover within one year, it would be extremely difficult for any intervention to demonstrate a superior result to this.”
Returning to STAR*D’s reported 67 percent remission rate, even within the psychiatry establishment, this rate was disputed as soon as it was published. The first critique of it appeared as an editorial in the same 2006 issue of the American Journal of Psychiatry that the STAR*D study had been reported. In this critique, “The STAR*D Study: A Four-Course Meal That Leaves Us Wanting More,” psychiatrist J. Craig Nelson notes that 67 percent remission rate did not account for relapse, nor for patients who discontinued treatment. Nelson stated the following: “Among those achieving remission, relapse rates [in Step 1 thru Step 4] were 33.5%, 47.4%, 42.9%, and 50.0% . . . . If the goal of treatment is sustained recovery, relapse should be considered. I found a cumulative sustained recovery rate of 43% after four treatments, using a method similar to the authors but taking relapse rates into account.”
When researchers outside of the psychiatry establishment began looking under the STAR*D hood, their conclusions about antidepressant effectiveness in the real world were the opposite of the STAR*D authors. One critique was authored by psychologists Allan Leventhal and David Antonuccio, published in 2009 in Ethical Human Psychology and Psychiatry; another was lead-authored by psychologist Edmund Pigott, published in 2010 in Psychotherapy and Psychosomatics (which was also reported on in 2010 by Medscape Medical News).
Among their most devastating STAR*D revelations was the uncovering 0f the following: Of the initial STAR*D cohort of 4,041 patients who started on Celexa, 370 dropped out within 2 weeks (foregoing $25 payments for future assessments); and from the remaining 3,671 patients, only 108 of them—or approximately 3%— had a “sustained remission” (in other words, they had remitted, stayed well, and did not drop out but remained in the trial for follow up).
Also uncovered in the STAR*D study were egregious methodological issues, including: inflating remission rates by, after the study began, switching from the pre-specified primary outcome measure (the HRSD) to another scale (QIDS-SR) as the primary outcome measure, a switch that inflated the remission rate; and including in the total remission rate those patients who remitted but weren’t depressed enough at baseline to meet study criteria.
What other antidepressant studies, unexamined by the Times, might have interested its readers? A 2022 large study, lead-authored by Marc Stone at the FDA’s Center for Drug Evaluation and Research, examined 232 randomized, double blind, placebo controlled trials on antidepressants (submitted by drug companies to the FDA between 1979 and 2016). Even in these drug-company studies, Stone and his co-researchers found that only “15% of participants have a substantial antidepressant effect beyond a placebo effect.” Moreover, drug company antidepressant trials submitted to the FDA are routinely short-term studies, usually around six weeks. In 2017, “Poorer Long-Term Outcomes among Persons with Major Depressive Disorder Treated with Medication,” published in Psychotherapy and Somatics, foundthat controlling for depression severity, the outcomes of 3,294 subjects over a nine-year period showed that antidepressants may have had an immediate, short-term benefit for some people, but at the nine-year follow-up, antidepressant users had significantly more severe symptoms than those individuals not using antidepressants.
Yet if all one knew about antidepressants was from the November 9, 2022 New York Times article, one would believe that in the real world, antidepressants are scientifically effective, and that “nearly 70 percent of people had become symptom-free by the fourth antidepressant.”
Psychiatry and the Widespread Belief in the Chemical Imbalance Theory
Furthermore, if all one knew about the serotonin imbalance theory of depression was from that November 9, 2022 New York Times article, one would believe that psychiatry has long known it was untrue but is not responsible for the fact that much of the general public has been unaware that it was disproven decades ago.
The Times reported that “starting in the 1990s, researchers began to understand that depression was much more complicated, and that serotonin played only a nominal role.” In response to Moncrieff’s review that concluded no evidence for the serotonin imbalance theory of depression, the Times quoted Daniel Iosifescu, a professor of psychiatry at N.Y.U. Langone Health, “To me, that is an old theory for depression. That was already invalidated 20 years ago, so we’re just essentially putting the nail in the coffin, so to speak.”
The Times uncritically accepted psychiatry’s claim that it is not their fault that the chemical imbalance theory of depression has continued to have widespread belief by the general public. The Times explained the theory’s persistence this way: “This so-called ‘chemical imbalance’ theory gained a foothold in the cultural psyche and was promoted by ads for the medications.” While Big Pharma certainly had a major role in maintaining the disproven chemical imbalance theory, the reality is that so too did psychiatry at its highest levels.
Journalist Robert Whitaker investigated whether or not psychiatry officialdom had proclaimed this chemical imbalance theory to be true long after the research had rejected it. In his August 2022 “Psychiatry, Fraud, and the Case for a Class-Action Lawsuit,” published in the webzine Mad in America, he documents the evidence that contradicts psychiatry’s claim. One of several examples he provides that contradicts this claim is the American Psychiatric Association (APA), in its 2005 publication for the general public, “Let’s Talk Facts about Depression,” stated: “Antidepressants may be prescribed to correct imbalances in the levels of chemicals in the brain”; and this claim continued to be stated for the next 16 years until 2021, when psychiatrist Ronald Pies reported that he managed to get the APA to delete that message.
Psychologist Philip Hickey’s 2014 review “Psychiatry DID Promote the Chemical Imbalance,” published in Mad in America, documents how prominent mental illness consumer organizations—with scientific advisory councils made up of the leading figures in psychiatry—continued to proclaim the chemical imbalance theory as fact after it had been disproven. Hickey documents that one the most well-know of these organizations, the National Alliance on Mental Illness (NAMI), stated in 2014 (since deleted): “Scientists believe that if there is a chemical imbalance in these neurotransmitters [norepinephrine, serotonin, dopamine], then clinical states of depression result.”
Whitaker notes that, “While many consumer organizations have now scrubbed such claims from their sites, they have not disappeared altogether,” offering the example of the Child Mind Institute, founded by prominent child psychiatrist,Harold Koplewicz, longtime editor-in-chief of the Journal of Child and Adolescent Psychopharmacology. Remaining on the Child Mind Institute website in “Medication for Kids with Depression,” it is stated: “Antidepressants usually work by balancing the levels of neurotransmitters—chemicals that send signals between neurons—in the brain. These chemicals include serotonin, dopamine, and norepinephrine. Higher levels of these chemicals usually correspond with lower levels of depression.”
STAR*D, Chemical Imbalances, and WMDs
What caused the New York Times to uncritically accept its sources’ claim that STAR*D is evidence of antidepressant real-world effectiveness? What caused the Times to uncritically accept the narrative that psychiatry has no responsibility for the public continuing to believe in the serotonin chemical imbalance theory of depression after it had been disproved? One reason appears to be the same reason that the Times famously got it wrong in its 2002 and 2003 reporting of weapons of mass destruction (WMDs) in Iraq.
On May 26, 2004, New York Times editors published an acknowledgement of failing their journalistic responsibility with respect to reporting about dangers posed by Saddam Hussein and WMDs (one of many such examples, its September 8, 2002 lead article headlined “U.S. Says Hussein Intensified Quest for A-Bomb Parts”). Below is an excerpt from this acknowledgement that is relevant to the Times recent report of psychiatry’s disproven claims:
“In some cases, information that was controversial then, and seems questionable now, was insufficiently qualified or allowed to stand unchallenged. . . . The problematic articles . . . . depended at least in part on information from a circle of Iraqi informants, defectors and exiles bent on ‘regime change’ in Iraq, people whose credibility has come under increasing public debate in recent weeks. . . . . Complicating matters for journalists, the accounts of these exiles were often eagerly confirmed by United States officials convinced of the need to intervene in Iraq. . . . Some critics of our coverage during that time have focused blame on individual reporters. Our examination, however, indicates that the problem was more complicated. Editors at several levels who should have been challenging reporters and pressing for more skepticism were perhaps too intent on rushing scoops into the paper.”
While readers of the New York Times assume that skeptical reporters and even more skeptical editors are zealously considering the motives and conflicts of interest of their sources, the fact of the matter, acknowledged by the Times, is that a lack of such skepticism resulted in the Times being used by those intent on regime change in Iraq.
The New York Times on November 8, 2022, in its “Antidepressants Don’t Work the Way Many People Think,” repeated the same mistake of a lack of skepticism about the motives and conflicts of interest of its sources.
For serious journalists and editors, it should be obvious that the institution of psychiatry was put into a difficult position by the widespread public attention of Moncrieff’s review that concluded no evidence for the serotonin imbalance theory of depression, and that the psychiatry establishment had a strong need for damage control to its credibility. And it should also be obvious that psychiatry, as an institution, has a powerful motive for declaring antidepressants to be very effective regardless of the lack of a neurobiological rationale of correcting a chemical imbalance—the rationale that has convinced so many people to use SSRI antidepressants.
Sadly, the New York Times, once again, evidenced no skepticism about declarations from sources with powerful motives to persuade the public to believe a self-serving narrative that is disputed by the evidence.