NOTAssir Ghaemi, professor of psychiatry at Tufts, recently responded to a systematic review we conducted of the evidence supporting the common claim that lithium prevents suicide.
The content and style of Ghaemi’s article, which is more of a diatribe than a scientific commentary, suggest that he was extremely upset that this cherished belief had been challenged (Ghaemi, 2022). The manner in which it was published in the Journal of Psychopharmacology This implies that he was not alone. As such, the article offers an interesting insight into the importance of the medical or disease model in addressing the identity of professional psychiatry.
Ghaemi, along with the reviewers and editors, seems compelled to defend the reputation of psychiatric drugs as sophisticated, targeted agents and to silence any idea that they are not so special. The article illustrates the desperate lengths to which some will go to defend this view and the way in which a group of biological psychiatrists exerts its influence on the scientific literature.
Our review of data from randomized trials was the largest to date and failed to support the claim that people treated with lithium have lower rates of suicide or suicide attempts than people treated with placebo (Nabi et al., 2022).
One of us (Joanna Moncrieff) designed this study because the belief that lithium prevents suicide is widespread and influential. The main evidence cited to support this belief came from a meta-analysis published in 2013, which excluded a large proportion of trials on the grounds that no suicides occurred (Cipriani et al, 2013). The technique of excluding trials with ‘zero events’ is problematic, however, because it excludes a lot of relevant data and makes suicide appear more common than it actually is. This technique was popular mainly because older statistical methods of meta-analysis could not accommodate such trials. So initially we planned to do a simple analysis, combining the data from each trial as if it were a single trial. Then Martin Plöderl joined the team and brought his expertise in the new statistical methods of meta-analysis that have been developed to handle ‘zero event’ trials. So we also applied them.
In a previous article, Ghaemi stated that lithium “is the only drug in psychiatry that has been shown to be disease-modifying,” meaning that it affects the pathophysiology of the disease process and the course of the disease, including suicide mortality. In contrast, according to Ghaemi, other psychiatric treatments are nonspecific, “symptomatic” treatments that have no effect on the underlying disease (Ghaemi, 2022).
Ghaemi’s classification of drugs is misleading. Symptomatic treatments may, however, target the physiological processes that produce symptoms. In fact, most medical treatments affect the mechanisms of symptoms rather than the ultimate pathology of a disease. There is, however, little evidence that psychiatric drugs do this. As one of us (Joanna Moncrieff) has explained in numerous publications and conferences (including one at which Ghaemi was a co-presenter), psychiatric drugs can modify the manifestations of mental disorders by altering normal biological processes (the drug-centric model). There is little justification for assuming that they have any additional impact on the hypothesized mechanisms that produce the feelings and behaviors we call symptoms of mental illness (the illness-centric model) (e.g., Moncrieff, 2008; Moncrieff, 2018). These mechanisms are not established and probably never will be, because mental illness typically consists of complex situations that are unlikely to be explained by a deterministic, mechanistic model of causation (Moncrieff, 2020).
So when Ghaemi claims that psychiatric drugs target symptoms rather than modify diseases, he is not saying anything that is inconsistent with the conventional medical model of psychiatric treatment.
But Ghaemi wants to argue that lithium is special: that it does more than target the mechanisms of symptoms, it modifies the disease process that underlies bipolar disorder.
Ghaemi is original in suggesting that only lithium affects the disease itself, but he joins the crowd of psychiatrists who regularly and authoritatively proclaim that we know the biological basis of major mental pathologies. Regarding bipolar disorder, Ghaemi states that “the basic pathophysiology is known to involve the biology of recurrence,” which he suggests involves systems affected by lithium (Ghaemi, 2022).
While most biological psychiatrists admit that we do not understand the biological basis of bipolar disorder (Harrison et al, 2018) or the mechanism of action of lithium (Chokhawala et al, 2024), they regularly make similar arguments to justify the disease-modifying effects of other drugs. Psychiatrists who protested the comprehensive study of serotonin and depression conducted by one of us (Moncrieff et al, 2022) insisted that there was no link between serotonin and depression. East There is some evidence of a link, although the overall picture is inconsistent and unconvincing (Jauhar et al., 2023), and others have used alternative theories to argue for disease-targeted effects of antidepressants and other drugs introduced to treat depression (such as esketamine) (Belko, 2024). At the recent annual conference of the Royal College of Psychiatrists, it was firmly stated that schizophrenia is linked to dopamine dysfunction, which would therefore respond to dopamine-blocking drugs.
Ghaemi believes that glutamate is responsible for schizophrenia, which is not affected by antipsychotics (Ghaemi, 2022). Coupled with his proposals about the foundations of bipolar disorder, this allows him to differentiate between lithium and antipsychotics in terms of their relationship to the hypothesized underlying illness.
But Ghaemi’s argument for lithium’s special status as a curative agent also rests on his claim that lithium reduces mortality, including suicide. It is therefore understandable that he would want to challenge our systematic review. It is less clear why he felt the need to be so pejorative and unprofessional in his response. We will describe some of the derogatory comments he makes, and then briefly provide a rebuttal of his substantive arguments, most of which were made in another, more civilized response to our review (Bschor et al, 2022) to which we responded (Moncrieff et al, 2022).
The title of Ghaemi’s recent article, “The Pseudoscience of Lithium and Suicide: Reanalysis of a Misleading Meta-Analysis,” is an insult before we even get to the text. The first sentence of the introduction repeats the claim that our analysis is “pseudoscience” and accuses us of spreading falsehoods and using “meta-analysis as a tool to deceive ourselves and others” (Ghaemi, 2024).
Ghaemi then explains the meaning of pseudoscience, for those who may not be familiar with it, and the process by which “pseudoscientists” deceive people:
“Pseudoscientists deceive themselves by adhering to a set of immutable beliefs. They can then deceive honestly, based on their own self-deception. Self-deception is a prerequisite for deception.”
In contrast, Ghaemi seems to present himself as the real scientist, claiming that “science is a much more difficult task than pseudoscience, just as refuting its beliefs is much more difficult than confirming them.”
In his conclusion, he hammers the point home further: “This kind of paper is not ‘research’ in the sense of new knowledge: it has produced no new data of fact. It is social activism disguised as science. It uses scientific journals as a public relations tool, lending a veneer of respectability to explicit opinion-based propaganda on the Internet and social media.” The fact that we may disagree with his views is presented as evidence that even if we “believe” we are doing science, we are “doing the exact opposite of science.” In doing so, “pseudoscientists first deceive themselves, and then seriously impose their false beliefs on others.” Ghaemi disabuses people of our misleading propaganda. “It takes a bit of attention to understand why their meta-analysis was wrong,” he explains, “but it is worth it if one seeks knowledge instead of deceiving oneself.”
Ghaemi was not, however, solely responsible for the tone of his paper. One of us was asked to review the initial version he had submitted to the journal. Instead of reviewing it, we suggested that we be invited to provide a response that would be published alongside the paper. This recommendation was also made by the Committee on Publication Ethics (COPE), whose role is to publicize the results of the study. Journal of Psychopharmacology We committed to doing so. Although we were initially informed that we would be invited to do so, we were ultimately not invited. Instead, the editor and reviewers not only facilitated the unscientific tone of the article, but also failed to correct obvious misrepresentations of our study.
In the original version of the article that was sent for review, the title was “Lithium and suicide: a critique and reanalysis of a recent systematic review.” The article mentioned pseudoscience, but very briefly. In the published version, the title was changed to include the charge of pseudoscience, and two new entire sections on “pseudoscience” were added to the text, one in the introduction and one at the end. Most of the explanations of our supposed misleading practices, criticisms of our scientific credentials, and pejorative language, such as references to “social activism,” “opinion-based propaganda,” and “questioning their beliefs,” were added later. These changes likely reflect suggestions from the reviewers or editors of the journal. The lead editors and editorial board include several biological psychiatrists who have spoken out against other work that challenges biological theory…
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