Doctors respond to criticism of study re: so-called low serotonin in depression

From Mad in America:

 

 

"Response to Criticism of Our Serotonin Paper

By Joanna Moncrieff, MD & Mark Horowitz - July 28, 2022

 

https://www.madinamerica.com/2022/07/response-criticism-serotonin-paper/

 

We recently published a paper finding that the serotonin hypothesis of depression (the idea that depression is caused by low serotonin or reduced serotonin activity) is not supported by scientific studies that have been conducted over the last few decades. The serotonin hypothesis was communicated to the public as the “chemical imbalance” theory of depression. In surveys, 85 to 90% of people in western countries report believing that depression is caused by a chemical imbalance.

 

We suggest that the idea that depression is caused by low serotonin or a chemical imbalance should no longer be communicated to patients as it is not supported by research.

 

This also brings into question what antidepressants are doing: if they are not correcting an underlying chemical problem, as people are often told (“like insulin for diabetes”), then other ways of understanding what they are doing, such as providing hope (the placebo effect) or numbing emotions (a common report by patients) may be more accurate descriptions.

 

Psychiatrists in Britain, some of them with career-long relationships with the pharmaceutical industry, responded to our paper’s findings and its implications here, which were then reported in several media pieces covering our paper. We would like to respond to these criticisms.

 

We would like to say first that no one should stop their antidepressant medication abruptly—this can be dangerous and is known to cause withdrawal effects, which can be severe and long-lasting in some people, especially those using the medications long-term. If anyone is considering this choice, we advise you to discuss it with your doctor and, if you go ahead, to undertake a gradual and supported reduction as advised by recent Royal College of Psychiatry guidance.

 

Contradictory responses—the serotonin imbalance theory was both never supported and also is still supported

 

There are a few remarkable aspects of the criticisms to note before we address specific critiques. The first is that the criticisms of our paper were contradictory, with some prominent psychiatrists saying that there was nothing new in our review (“really unsurprising,” “not news”) as it was already understood that depression was not caused by low serotonin. However, other psychiatrists said it was “premature” to dismiss the serotonin hypothesis and that further studies are required (despite this hypothesis having been studied for more than 50 years now). The existence of contradictory viewpoints reveals the cognitive dissonance in the field.

 

Disconnect between the public and psychiatrists

 

The second notable fact is how disparate the response was from psychiatrists and the public, with most psychiatrists shrugging off the finding as a straw man by saying “I don’t think I’ve ever met any serious scientists or psychiatrists who think that all cases of depression are caused by a simple chemical imbalance of serotonin” and that they are “broadly in agreement with the authors’ conclusion about our current efforts.”

 

In contrast there has been an avalanche of interest from the public—with more than a million reads on The Conversation, and widespread media coverage, so that our paper is now amongst the top 600 papers ever shared (out of 21 million papers that have been tracked). This interest likely stems from how widespread the message is that depression is caused by a chemical imbalance and that antidepressants work by fixing this imbalance. Many people, including journalists, have been shocked to find out this is not true, with one presenter commenting “it blows your mind.”

 

It may well be the case that psychiatrists have a more “sophisticated” understanding of the role of serotonin than the lay public, but psychiatrists have failed to correct this misunderstanding. Several academics have said that “we never told anybody this explanation.” However, the public clearly is being given this explanation: in England last week, a doctor on BBC radio told the public that in depression “there is a chemical imbalance and antidepressant given at the right time will help with that chemical imbalance.” The same message was given to the public on a leading UK morning television programme earlier in the year by another doctor. It is not surprising that the vast majority of the general public (as shown in surveys) believe this message to be an established scientific fact.

 

We know from our analysis of textbooks and journal articles that the idea of low serotonin (the “chemical imbalance”) was widespread in medical literature and remains so in many current textbooks. It was only recently that the Royal College of Psychiatrists in Britain removed its reference to chemical imbalances, describing the theory as an “oversimplification,” but without explaining that there is no proof for low serotonin levels, or indeed for any other neurochemical theory of the causes of depression. The American Psychiatric Association continues to tell the public that “differences in certain chemicals in the brain may contribute to symptoms of depression.”

 

Psychiatrists fail to appreciate the enormous impact for patients of being told that depression is caused by a chemical problem in the brain and that antidepressants can fix this problem. Skating over this issue to turn to alternative hypotheses about the cause of depression or the mechanism of action of antidepressants neglects to address the fact that patients have been misled. It is alarming to hear that there is a problem in your brain and it is misleading to suggest that we know there are drugs which can fix it.

 

This narrative strongly encourages people to take antidepressants because it seems wholly rational to take a drug which reverses an underlying chemical problem; indeed, it seems irresponsible not to do so. What is being dismissed as trivial semantics by experts has had consequences for the life choices and self-perception of hundreds of millions of patients worldwide. Imagine being told that you had a major problem in your heart that required medication to fix—only to find out that that problem was not truly there.

 

For the public, the chemical imbalance has been no straw man or semantic approximation, but something that has guided the direction of their lives, choices, and health. We know that believing that your depression is caused by a chemical imbalance tends to make people more pessimistic about recovery (seeing their symptoms as more chronic and intractable), leads them to believe they have less ability to regulate their moods, and also leads them to believe that medication is a more credible solution than therapy. We should actively counter this myth and remove it from medical information conveyed to patients because it is not supported by evidence.

 

The mechanism of action of antidepressants does not matter, as we know that they work

 

The other argument raised by critics was that even if antidepressants are not rectifying an underlying chemical problem, they can still be effective by modifying neurotransmitters—and we use many medications whose mechanism we don’t understand. Some critics have said “Many of us know that taking paracetamol can be helpful for headaches and I don’t think anyone believes that headaches are caused by not enough paracetamol in the brain. The same logic applies to depression and medicines used to treat depression.”

 

First of all, the analogy is misleading because we know that paracetamol works by targeting the mechanisms that produce pain, and it does not produce an alteration in normal emotions and mental experience. With antidepressants, we do not have evidence that they target the underlying biological basis of depressive symptoms, and they do produce mental and emotional changes which can account for their effects.

 

Secondly, we would suggest that how a drug works, or what exactly it does, is crucially important in evaluating whether it is useful or not. With a drug that modifies brain chemistry in ways we do not fully understand, it would be wise to take a cautious approach and be wary of using it for long periods of time on a continuous daily basis. This is a very different proposition from taking a drug that reverses an underlying deficiency.

 

With antidepressants, we are looking for heuristics, or rules of thumb, to make sense of what these medications are doing in the context of short-term randomised trials that show marginal differences from placebo (with the vast majority of studies lasting less than 12 weeks). The idea that medications work by rectifying an underlying imbalance is very reassuring. Indeed, who would decline such a “lock and key” treatment? And this seemed to have been the marketing strategy of drug companies in propagating this line. For instance, we are not overly worried about long-term use of insulin in diabetes because supplementing a naturally occurring chemical back to normal levels seems unlikely to be a harmful approach.

 

However, if the approach to treatment is now reframed as altering brain chemistry in a system that has no underlying detectable problem (or involves a complex and nuanced alteration of serotonin as yet poorly understood) then we are faced with a very different proposition. The human brain has evolved over millions of years and involves thousands of inter-dependent chemical systems to regulate processes in the body and brain. It is a valid question to ask: what is the effect on the brain of modifying the action of a neurotransmitter in this complex, inter-dependent system, especially in the long term?

 

We may be guided in answering this question by the effects of other substances that affect mental processes such as thoughts and feelings, including recreational drugs like alcohol. These tend to cause tolerance from repeated use, and withdrawal effects when they are stopped; this combination is usually termed physical dependence (a state distinct from addiction). Most such drugs also have detrimental effects on things like concentration and memory when they are used frequently or continuously. We know that these theoretical concerns are borne out in practice with the use of antidepressants: there are withdrawal effects—which can be severe and long-lasting in some people—and negative impacts on memory, concentration and sleep, not to mention sexual and other physical adverse effects.

 

 

 

The paper continues, and the full paper can be viewed at the link:

 

https://www.madinamerica.com/2022/07/response-criticism-serotonin-paper/

It looks like that paper ruffled some feathers, GOOD! Thanks Lapis2, excellent work as usual.

It looks like that paper ruffled some feathers, GOOD! Thanks Lapis2, excellent work as usual.

 

It certainly did, Pamster! I think this rebuttal article is fantastic, though. I highly recommend that people read the whole thing. So well written and so illuminating. I do hope the doctors' detractors take a few minutes to read it.

I don't know why doctors find this study surprising or controversial. Anyone reading these drug studies and paying attention would have long suspected that low serotonin isn't the sole (or even major) cause of depression.

 

How many studies of SSRIs and SNRIs do you have to read where the active arm of the study just barely outperforms the placebo arm till you question whether the low serotonin = depression theory is correct?

 

I don't know why doctors find this study surprising or controversial. Anyone reading these drug studies and paying attention would have long suspected that low serotonin isn't the sole (or even major) cause of depression.

 

How many studies of SSRIs and SNRIs do you have to read where the active arm of the study just barely outperforms the placebo arm till you question whether the low serotonin = depression theory is correct?

 

I think that's the key point there Nathan, how many doctors do you think actually read studies? Most have been taught that antidepressants treat depression, and that's that. I read 1 psychiatrist say, "it doesn't change the fact that they help people". So still, they are not interested in how or why. They use antidepressants for depression. They are simply not interested enough to question it

I was listening to the radio a couple of days ago when they were discussing "treatment-resistant depression". That term made me shudder. So....if you don't get better with whichever antidepressant they gave you, then they will give you another, and another, and another, until you get the label "treatment-resistant depression". There's no mention of the effect of trying multiple meds or withdrawal or side effects.

 

As well, the person is then given a label which makes them feel damaged and unable to ever get better without some sort of miracle, because they drugs they were given didn't make them feel better. No one questions the efficacy of the medications or the theory underlying their use.

 

An unbelievably sad story, in my opinion.