Last summer, a thorough analysis revealed the following: psychology today called “Decisive blow” To the myth of the chemical imbalance of depression. The outdated theory that serotonin deficiency causes depression error exposed many times beyond the past decadesbut it clings to the public consciousness, probably mainly because: Pharmaceutical industry propaganda and Oversimplification of media. that’s right, A prominent psychiatrist also claims that The serotonin theory anti-psychiatry conspiracy.
Given such a position, psychiatry would welcome a large-scale review of the evidence on the subject (the largest and most comprehensive one ever undertaken), and the supposed anti-psychiatric propaganda Some might think that it would put an end to Rather, the reaction from psychiatry has been acrimonious to the author.
Researchers who are betting their economic future on the serotonin theory are now collaborating to try to debunk their work. the only problem? According to the original study authors, their concerns are highly technical, contradictory, and in some cases downright erroneous. None of them provide solid or consistent evidence for the role of serotonin in depression.
In fact, petty and paradoxical complaints by various critics, including pharmaceutical company CEOs, are likely to help market new drugs, but cling to outdated theories that are undersupported and controversial. It highlights the reality of industry-funded researchers in the field.
In response to this criticism, the authors of the original study wrote of the serotonin theory that “no one believes it, but no one wants to let it go.”
Critics of the serotonin debunking study and the original authors responded, molecular psychiatry.
The authors of the original paper are Joanna Moncrieff, Ruth E. Cooper, Tom Stockmann, Simone Amendola, Michael P. Hengartner, Martin Plöderl, and Mark A. Horowitz.
To summarize Mr. Horowitz’s criticism: Tweeted:
Some argued that the serotonin hypothesis of depression was long ago dismissed, others still supported it, and some argued both. response was confusing. @joannamoncrieff @hengartnerMP @ploederlM https://t.co/kfd88bqbxw
— Mark Horowitz (@markhoro) June 16, 2023
“Some argued that the serotonin hypothesis of depression was long ago dismissed, others still supported it, and some argued both, so the critics of our paper The response to was extremely confusing.”
Critics include Jacob Jacobsen, founder and CEO of Evecxia Therapeutics, a company he set up to market his serotonin-targeting drugs, and a large group of authors led by Sameer Jauhar. They have a list of financial conflicts of interest. The pharmaceutical industry consists of a few pages in small print. These critics argued that serotonin should be considered the primary cause of depression. Even if we were unable to provide such valid or consistent evidence.
Other critics say that serotonin itself Although not related to depression, serotonin precursor is the cause. They argue that a complex and poorly understood system involving every part of the brain is involved in depression, and that system inevitably includes the serotonin system.
A final critical paper is by Rif S. El-Malak et al., who admit that the serotonin theory of depression has long been false, but argue that the Moncrief et al. theory is false. ing. It is wrong to draw attention to how this undermines the evidence base for antidepressants.
Some critics have therefore written that it is clear that low serotonin is still the cause of depression, despite being unable to provide evidence. Others have written that despite being unable to provide evidence, it is clear that depression is caused by a complex system that we do not understand (although serotonin is certainly involved). Some people write that we know serotonin is irrelevantthe efficacy of the drug should not be doubted on the basis of this regime.
In fact, the defense of SSRI antidepressants seems to be the main concern of critics. For example, Jauhar et al. write, “The demonstrated effectiveness of SSRIs in some people with depression adds credibility.” [to the serotonin imbalance theory]”
In response, Moncrieff et al. write that the efficacy of SSRIs has been rather hotly debated, far from being “proven” as is often the case. Can’t beat placebo For treating depression.Even if they beat the placebo, it small margin it is conceivable Clinically undetectable. This may be due to an enhanced placebo effect, or effects that are not true depression-targeted effects, such as emotional numbing.
Furthermore, just because a drug treats a symptom does not mean that the symptom is caused by a deficiency of that drug. People “self-medicate” with alcohol to relieve mood and anxiety problems, but that doesn’t mean that alcohol deficiency can be successfully treated.
“From a lay person’s perspective, taking drugs that are thought to reverse underlying chemical imbalances and other brain abnormalities is imperfectly known and potentially unpredictable. It’s an entirely different prospect than taking a drug that disrupts brain chemistry in any way possible and whose effects on the brain have not been well studied: moods and behaviors are altered, and emotional numbness manifests itself as an obvious effect. However, this approach of marketing medicines by exploiting the unproven and implausible hypothesis of a single neurotransmitter to provide biological justification for its use is rapidly following. ,” write Moncrief et al.
Perhaps the most unscientific criticism, according to Moncrief and colleagues, is the idea that serotonin is a key link in a complex interlocking brain pattern that we have barely begun to understand. Saying that something must be true because it is too complex to understand does not constitute a valid or testable scientific theory.
“Although it appears scientific, the hypotheses presented are too vague and comprehensive to be fully tested,” Moncrief et al. write.
Other criticisms included controversy over study inclusion and exclusion criteria in the original review by Moncrieff et al., and objections to the type of assessment used to assess study quality. However, Moncrieff et al. responded that their criteria were clearly stated in the original article and that they followed validated guidance on how to use these ratings, and indeed Jauhar et al. ‘s criticism is in fact clearly false.
“It is not true, as claimed by Jauhar et al. used STREGA for genetic studies and GRADE to assess the certainty of findings, all validated and widely used measures.In fact, cited by Jauhar et al. The following are examples of umbrella reviews that use the same quality rating scale, AMSTAR, and a reliability classification similar to GRADE, which includes criteria for sample size and the presence of bias. I have.”
Finally, many critics cited small, biased, non-replicated studies of serotonin-related biological processes to argue that Moncrief et al.’s work was correct. We have handpicked the results in favor of their views. Again, however, the inclusion and exclusion criteria used by Moncrieff et al. These additional studies do not provide convincing evidence for a link between low serotonin and depression, they write. In fact, this is an example of a selection of studies endorsed by critics who have not done a systematic review. their Quarrel.
as moncrief explained on twitter:
In conclusion, Jauhar’s points (which are mostly wrong) do not make any difference between our findings and our conclusions. There is no evidence of decreased serotonin and weak evidence of increased serotonin, which is probably explained by previous drug use. 26/28
— Dr. Joanna Moncrieff (@joannamoncrieff) June 26, 2023
“Jauhar’s points (although most of them are wrong) do not make any difference to our findings or conclusions. Yes, but this is plausibly explained by previous drug use.”
she added,
“Jauhar and his colleagues cannot make a compelling case, but they are desperate to discredit our research to continue perpetuating the myth that depression has an established biological basis. .”
In conclusion, Moncrieff et al. again summarize their research needs.
“The reason our paper is important is that the pharmaceutical industry, like many physicians and academics, is working to justify the use of antidepressants and to overcome resistance in some people. We’ve told the public for decades that it’s caused by psychopathy,” using mood-altering drugs. Our paper debunked this claim. The major research areas do not support the best-known neurochemical hypothesis, the serotonin theory of depression, the idea that depression is caused by low levels or activity of serotonin. “
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Moncrief, J., Cooper, RE, Stockmann, T., Amendola, S., Hengartner, MP, Prudall, M., and Horowitz, MA (2023). The Serotonin Hypothesis of Depression: Long Ignored, Still Supported? molecular psychiatry. Published online June 16, 2023. https://doi.org/10.1038/s41380-023-02094-z (Link)
