Drug regulator thinks it’s reasonable to mislead people about chemical imbalance in depression

In a reply to a letter from Peter Gøtzsche, the Medicines and Healthcare products Regulatory Agency (MHRA) has made clear that it has no current plans to remove the references to chemical imbalance in the Patient Information Leaflets (PILs) of antidepressants (see reply). A previous reply to a freedom of information request has helped to clarify the history of the introduction of this term into such PILs.

The chemical imbalance theory of depression has never been more than a hypothesis (see eg. previous post). The trouble with MHRA maintaining its position is that it gives credence to the idea that the hypothesis has been proven, which is clearly not the case. It seems willing to let people be misled about the nature of depression. Its bias in promoting antidepressants needs to be exposed.

Easy solutions to psychological problems?

Psychological problems are common. People don't always adjust to difficulties in life and relationships very well. They don't always meet their own or others' expectations of how they should function socially.

Solutions on offer to psychological problems from mental health services, such as psychotropic medication and talking therapy, may, therefore, seem attractive. This can mean that the limits to treatment are not always acknowledged or recognised. Wishful thinking can be powerful and self-fulfilling.

The trouble is that this situation means that providing increasing resources for mental health services can never meet the perceived need of the population  (see eg. my BMJ article with corrections - see previous post). Psychological problems are real and the role of mental health services is to respond to them and provide care until normal social roles can be resumed. No wonder mental health services are in difficulty if they think that panaceas to mental health problems are the answer (see eg. another previous post). 

Psychiatry is doomed to conflict about the value of psychiatric medication

Doctors have always exaggerated the advantages of medication. But medication, including recreational drugs, can’t just be eliminated. There are plenty of people that say that psychiatric medication has helped, despite its disadvantages (see eg. previous post). This experience cannot be denied, even if it is due to the placebo effect. Mainstream psychiatry will never accept that psychiatric medication is not effective.

What may be more important is that people are being misled about the nature of mental health problems (see eg. previous post). People are more than their brains. Of course brain abnormalities can produce mental health problems, such as dementia and delirium. But most mental health problems are not due to brain abnormalities.  People are limited by their bodies, true. But it’s their social experiences that determine how mental health problems present. This may be because of their past or present experiences. It’s important to try and understand why people have mental health problems because of their experiences, even if the causes can’t be proven as such. Trouble is that people are looking for definitive answers, which is why they latch onto the idea that mental health problems may be due to their brain. 

Psychiatry will continue to take advantage of people, including prescribing them medication. But it needs to change to be more focussed on people rather than its own prestige and financial interests (see eg. previous post). 

Sticking to the argument about whether antidepressants work

I worry that the clash between Joanna Moncrieff and Awais Aftab about her new book Chemically imbalanced has become too personal (see eg. last post). For example, Awais’ recent blog post criticises Jo for her methods rather than necessarily actually what she says. In many ways, how Jo expresses her critique is irrelevant. What matters is the content of what she says.

Awais Aftab wants to see integrative and critical pluralism as a variant of critical psychiatry (see previous post). But he’s only semi-critical and does not follow through properly on his critique. And he believes antidepressants and other psychotropic medications work, whereas critical psychiatrists such as Jo, are more sceptical, if not convinced of their non-effectiveness, which Jo has been brave enough to say.

As we saw with the Simon Wessely debate with Jo on the This morning TV programme (see clip), mainstream psychiatry will not allow Jo to say that antidepressants do not work. I have always been cautious about making such a definitive statement, even if expressing to people, including my patients, my belief that it may well be true. I’m not sure how to prove the so-called placebo amplification hypothesis even if I agree with Jo that there is considerable evidence in its favour (see eg. previous post).

Indoctrinating people into taking antidepressants

People are being misled about the nature of mental illness. Of course brain abnormalities can cause organic mental illness, such as delirium or dementia. But most presentations of mental health problems are not caused by brain abnormalities. 

Using depression as an example, people have been encouraged to see depression as a chemical imbalance in the brain. Because SSRI antidepressants are said specifically to block reuptake of serotonin from the synaptic cleft between neurones, it has been suggested that they must be correcting a serotonin deficiency in the brain. Although doctors may have realised that such an explanation of the effect of antidepressants is at least an oversimplification, they have allowed the general public to go along with the idea. In fact people have often believed the chemical imbalance theory to be proven. They have accepted, even been told, this myth to provide a reason for needing to take their antidepressants. Hence the controversy created by Joanna Moncrieff’s recent book Chemically imbalanced: The making and unmaking of the serotonin myth (see eg. previous post and Jo’s response). 

More generally, depression tends to be seen as a brain disease. Of course people recognise that personal and social factors may also be important, but still the brain causation of depression tends to predominate as an aetiological factor. This is a fundamental misindoctrination of people that their brains determine what they think, feel and do. Of course the brain is needed for human functioning, as is the whole body, but people are more than their brains. It is a mistake to blame the brain for depression as much as it is for what we think, feel and do in general. We are not teaching our children a proper understanding of themselves (see eg. previous post). No wonder the demand for children’s mental health services, and mental health services in general, is out of control (see eg. another previous post). 

Depression is real but not a concrete thing

Functional mental illness is an abstract not concrete concept. It differs from organic mental illness where there is brain dysfunction.

Illnesses tend to be seen as “things” which people “have” (see eg. previous post). Since the nineteenth century with the elucidation of pathological mechanisms, our positive understanding has become that the “thing” that people “have” is a diseased organ or bodily system. This model fits for organic mental illness such as dementia or delirium. For example, organic mental illness can be caused by a primary brain disorder or be secondary to a systemic illness. But functional mental illness, such as depression, is not primarily due to brain disease, although it can arise as a secondary consequence of illness. People are depressed, not their brains.

People of course are not separate from their bodies. They are alive, not machines, and embedded in their environment, which is social and cultural. Their bodies and environment afford various possibilities of action to them. Mechanistic dysfunctions of body parts may help to explain disease and why the person is ill. But the experience of illness is not necessarily due to diseased body parts. 

Depression, therefore, needs to be understood as a personal illness not a bodily disease caused by brain dysfunction. Its social implications can mean that various roles cannot be fulfilled, such as being able to go to work. It is not simply curable by willpower and motivation and, therefore, the person themselves should not be blamed for their illness. The expectation is that people will try to recover as quickly as possible with appropriate help and care if necessary. 

None of these social implications of illness necessarily require the presence of bodily disease to be entitled to the rights and obligations of the sick role (see eg. previous post). Such illness is not concrete in the sense of being caused by bodily mechanisms. But, functional mental illness, such as depression, even though abstract rather than concrete, is still real and valid. Regarding depression as a physical thing in the brain is a category error and does not make sense (see eg. previous post). 

The disadvantages of antidepressants

As I’ve said before (see eg. previous post), I’m inclined to believe that antidepressants are no better than placebo. I can’t prove this but it is possible that the statistical difference between antidepressant and placebo in short-term clinical trials is an artefact because of methodological problems, such as unblinding (see eg. another previous post). Nor do antidepressants over the long-term necessarily produce good outcomes (see yet another previous post). Treating depression is not always as easy as we might hope. 

I just wanted to elaborate on what the consequences are if antidepressants are really no better than placebo. Of course the nature of placebo in this sense is that it is given inadvertently (see eg. my BMJ letter). Doctors do not knowingly prescribe antidepressants as placebos. In fact, as advocates of antidepressants they can react vehemently against suggestions that antidepressants do not work (see eg. previous post). Nor do patients assume that antidepressants are placebo, perhaps especially if the medication has a positive effect. They are more likely to ascribe any improvement to a true antidepressant effect of the medication. Faith in antidepressants is commonly reinforced by the belief that medication improves a brain problem causing depression such as a chemical imbalance (see eg. another previous post). 

I’m not wanting to undermine people’s faith in medication. It’s important we have a balanced view of the advantages and disadvantages of antidepressants (see eg. previous post). We have to live with the uncertainty of the ongoing debate about the efficacy of antidepressants (see eg. another previous post), however much some people may want to close that debate down and conclude that antidepressants are definitely effective.

If we have to accept the uncertainty about the advantages of antidepressants, perhaps looking at the potential disadvantages will help us better assess their value. Doctors have always underestimated the difficulties in withdrawing from antidepressants (see eg. previous post) and the extent to which doctors are making people dependent on antidepressants (see eg. another previous post). Patients are not always warned about the risks of stopping antidepressants when they first start them, which they should be. Even if doctors routinely provided this warning, people can still naturally become fearful that discontinuing medication may upset the mental equilibrium they have managed to achieve with antidepressants after being depressed (see yet another previous post). Patients may believe the antidepressant is maintaining that equilibrium, whether it has been the cause of the improvement or whether changes have happened for other reasons. In other words, people can form attachments to their medication more because of what they mean to them than what they actually do (see my article). Any change threatens an apparent stability related to the meanings that the medications have acquired over time. It may, therefore, be easier to stay on medication than stop it. Considering also the difficulties people can have when they do try to stop, it is not surprising that people can stay on medication for long periods of time. They can be left in a vicious cycle of wanting to discontinue medication but feeling compelled to continue. 

Furthermore, people can often be left with the sense that antidepressants have masked the real problem or altered their experience of themselves and relationships with others (see previous post). This is to be expected if antidepressants act as placebos, because taking antidepressants in a way masks the ‘real problem’. This experience is commonly expressed by patients as a flattening of emotional responses or emotional numbing (see eg. another previous post). 

Withdrawal problems and not feeling one has made a proper recovery are high prices to pay for taking antidepressants. It’s understandable people are attracted to the offer of antidepressant medication relief from what may well have been a desperate situation when depressed. However, if we can’t necessarily say that antidepressants are any better than placebo, and the medication can leave people with these drawbacks, which are caused because antidepressants are placebos, then have they really helped? More people seem to be deciding the harms caused are not worth starting antidepressants.

The sorry state of modern academic psychiatry

I’m not sure who advised the king about the appointment of Ed Bullmore as Regius Professor of Psychiatry at the Institute of Psychiatry, Psychology and Neuroscience (IoPPN) at King’s College London (see announcement). I wrote a satirical, even rude, review of Bullmore’s book The inflamed mind a few years ago (see previous post). As I’ve always said, psychiatry has been too dominated by biomedical psychiatrists, like Bullmore (see eg. previous post). I haven’t always been totally complimentary either about Simon Wessely, the first incumbent of the Regius post (see eg. previous post). Nor do I think he’s made as much of reforming the Mental Health Act (see another previous post) as he had the opportunity to do (see yet another previous post). 

As I said in another previous post, modern academic psychiatry started in this country with the appointment in 1948 of Aubrey Lewis as Professor of Psychiatry at the Maudsley Hospital medical school, which changed its name to the Institute of Psychiatry, now IoPPN. Lewis had a much more sceptical scientific approach to psychiatry than Bullmore. Academic psychiatry’s emphasis has changed to be more biomedical since the start of the psychopharmacology era in the 1950s (see eg. another previous post). The limits of biomedical research do need to be recognised (see eg. yet another previous post), but I’m afraid Ed Bullmore will not lead the necessary changes.

Emotional blunting more a reflection that antidepressants don’t work than how they do

I’ve mentioned before my concerns about the notion that antidepressants work through being emotional suppressants (see eg. previous post). In fact, I’m more inclined to think antidepressants don’t work any better than placebo (see eg. last post), so there’s no need to explain how antidepressants ‘work’, as such. Although the emotional numbness theory has been promoted by Joanna Moncrieff, in her recent book she does qualify this hypothesis by saying she thinks “we should be cautious about assuming emotional numbing can be useful”. 

I’m more inclined to see emotional numbing as a reflection of the fact that antidepressants don’t work, than as an explanation for how they do. Many people are left feeling emotionally numb after being on antidepressants, particularly long-term (see eg. previous post). There is a sense in which taking antidepressants masks the real problem, particularly if depression is understood as physically caused, for example by a chemical imbalance, rather than having psychosocial origins. One’s view of oneself can be at stake in taking antidepressants (see eg. previous post). Undermining of emotional authenticity is not necessarily beneficial. Believing antidepressants are helpful may seem to produce apparent improvement, for example by counteracting demoralisation, but over the longer term such a perception may also leave people feeling dulled, numbed, flattened, blocked, blank, flat or apathetic, affecting their relationships with others and how they see themselves. Many people do initially feel released from these constrictions when they first stop antidepressants, but are then left with the difficulties of managing without them, which may well not be easy, because they have become so dependent (see eg. previous post).

Confusing brain and placebo effects of antidepressants

Jo Moncrieff in her new book Chemically imbalanced (see eg. previous post) discusses Peter Kramer’s 1993 book Listening to Prozac (see Wikipedia entry), which I mentioned in a previous post. As the New York Times said at the time (see article) Kramer’s best seller described “how Prozac … transformed his patients, making them calm, confident, cheerful and somehow better than well”. Jo admits that the miraculous transformations reported could have been “largely a function of the hype accompanying the introduction of a new medication” in the same way “as those described by Roland Kuhn in relation to imipramine” (see previous post). But she also uses Kramer’s book to support her speculation that antidepressants reduce people’s emotional sensitivity.

I have expressed concern before about how Jo talks about SSRIs causing emotional numbing or reduced emotional sensitivity (see eg. previous post). I agree there is a sense in which the placebo effect does not really deal with people’s underlying emotional problems. But Jo wants to argue that antidepressants work through their brain effects as well as their placebo effects. This is because she wants to build on her distinction between the disease-centred and drug-centred models of psychotropic drug action. I think it is possible to have an outcome-based understanding of antidepressant drug action without necessarily postulating that antidepressants work through their brain effects (drug-centred model in Jo’s terms) (see previous post). Antidepressants can be powerful placebos because of their effects caused through how people understand them (see eg. previous post).

Psychiatry misleading the public about chemical imbalance in depression

Awais Aftab has responded (see his blog post) to the Sunday Times magazine article about Joanna Moncrieff (see eg. previous post). He raises various useful questions about Jo's position but tends to be very critical of her perspective. It's possible some of the questions he raises may be answered in Jo's new book, due to be published this week. Nonetheless, Awais accepts that the "chemical imbalance story as it existed in the public imagination has little scientific legitimacy".

However, Awais seems to want to exclude psychiatry from any responsibility for people believing the chemical imbalance theory of depression. This seems difficult to justify (see eg. previous post). Awais admits that the chemical imbalance theory has been so vague that it has been left "up to patients and the public to make of it what they want". Why has psychiatry allowed this situation to continue? It must have suited its interests. I have always argued that psychiatry allows, even perpetuates the myth, because it wants people to take their medication (see eg. my BMJ eletter). Psychiatry is so wedded to the notion of antidepressant effectiveness that it allows people to be misled by how antidepressants work (if they do).

Of course psychiatry will say that even though the chemical imbalance theory is too simplistic, then antidepressants still work through their effects on the brain. Even this claim needs to be challenged (see last post).

Daring to argue that depression is not a physical disease

I mentioned the Sunday Times magazine article about Joanna Moncrieff in my last post, where I focused on the issue of whether antidepressants work. I also wanted to pick up what the article says in its introductory rubric about Jo daring to argue that depression is not a physical disease.

At face value, saying that depression is not a physical disease may not appear to be so much of a challenge to psychiatry. After all, depression is a mental not a physical illness, isn’t it? Why should psychiatry find such a view so threatening?

Jo emphasises in the article that making appropriate changes in one’s life is a way of tackling depression. Mainstream psychiatry does not always promote such social treatment of depression. Instead it encourages antidepressant medication, which tends to rely on regarding depression as a physical illness. Antidepressants tend to be seen as having physical effects on the brain, correcting, or at least helping to correct, the brain problem causing depression. Even if no brain abnormality is hypothesised in depression, antidepressants are still regarded as affecting or improving brain functioning. 

The chemical imbalance theory is therefore a way of promoting the idea that antidepressants counteract the brain problem causing depression. Most psychiatrists, if pressed, will admit this theory is too simplistic (see eg. previous post). But nonetheless they continue to look for brain abnormalities in depression, even being unprepared to give up implicating serotonin in the mechanism (see eg. another previous post). 

Psychiatry has always been caught in the philosophical mind-body problem. There has always been a fundamental conflict between psychic and somatic approaches to mental illness. It’s just that mainstream psychiatry has become too dependent on physical approaches, particularly over recent years with the development of psychopharmacology. This is why it finds it such a challenge that psychotropic medication may be no better than placebo, as I discussed in my last post.

I have always argued that psychiatry should not find such a challenge so threatening (see eg. my edited Critical psychiatry book). Before the psychopharmacology era, psychiatry did have a broadly conceived view of mental illness as being psychosocially caused. Of course this did not mean that physical factors were ignored. But most presentations to psychiatrists were accepted as having functional rather than organic causes. Over recent years this differentiation has become fudged (see eg. previous post). In fact, DSM-IV wrongly abolished the distinction (see eg. another previous post). Psychiatry is too keen to avoid metaphysical questions about how the mind relates to the brain.

The trouble is that this means that people can be reduced to their brains. The truth is that primary mental illness cannot be reduced to brain disease (see eg. previous post). Brain language has wrongly permeated our conception of ourselves over recent years (see eg. another previous post). But altered subjective experiences and disturbed reactions to others are essential elements of functional mental illness and not merely epiphenomena of a causal organic process. As I keep saying, psychiatry must stop reducing people to their brains. Restricting its interventions to psychopharmacology inevitably does so.

The legitimacy of asking whether antidepressants work

The Sunday Times magazine has an article about Joanna Moncrieff promoting the publication this week of her new book, Chemically imbalanced: The making and unmaking of the serotonin myth. This follows the 2022 umbrella review, of which she was the first author, which concluded that there is no consistent evidence of an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations (see previous post). This conclusion has caused controversy within mainstream psychiatry that wants to hold on to the idea that serotonin is implicated in depression (see eg. another previous post). This is because it believes that antidepressants work and wants to suggest that their effect on the serotonin system must be something to do with the mechanism.

The efficacy of antidepressants is a legitimate scientific question and my reading of the evidence is that the issue is still open, despite mainstream psychiatry’s insistence the issue is closed. Jo is not convinced antidepressants have any use. There is little doubt that short-term trials of antidepressants on average show a small significant difference above placebo. But because of methodological problems with the clinical trials this apparent benefit may be an artefact (see eg. previous post).

The placebo effect is powerful. Doctors have always exploited the placebo effect. Their beliefs and hopes about treatment, combined with patients’ suggestibility, can have an apparent therapeutic effect. Participants’ subjective beliefs about receiving active or placebo treatment in a clinical trial can significantly influence the assessment of the outcome of treatment. Whether antidepressants are mere placebo treatment is, therefore, a legitimate open scientific question (see eg. previous post). It should be possible to have this debate in public without having to label Jo as notorious.