Our umbrella review that revealed no links between serotonin and depression has caused shock waves among the general public, but been dismissed as old news by psychiatric opinion leaders. This disjunction begs the questions of why the public have been fed this narrative for so long, and what antidepressants are actually doing if they are not reversing a chemical imbalance.
Before I go on, I should stress that I am not against the use of drugs for mental health problems per se. I believe some psychiatric drugs can be useful in some situations, but the way these drugs are presented both to the public and among the psychiatric community is, in my view, fundamentally misleading. This means we have not been using them carefully enough, and crucially, that people have not been able to make properly informed decisions about them.
Much public information still claims that depression, or mental disorders in general, are caused by a chemical imbalance and that drugs work by putting this right. The American Psychiatric Association currently tells people that: “differences in certain chemicals in the brain may contribute to symptoms of depression”. The Royal Australian & New Zealand College of Psychiatrists tells people: “Medications work by rebalancing the chemicals in the brain. Different types of medication act on different chemical pathways.”
In response to our paper finding that such statements are not supported by evidence, psychiatric experts have desperately tried to put the genie back in the bottle. There are other possible biological mechanisms that could explain how antidepressants exert their effects, they say, but what really matters is that antidepressants ‘work’.
This claim is based on randomised trials that show that antidepressants are marginally better than a placebo at reducing depression scores over a few weeks. However, the difference is so small it is not clear it is even noticeable, and there is evidence it may be explained by artefacts of the design of the studies rather than the effects of the drugs.
The experts go on to suggest that it does not matter how antidepressants work. After all, we do not understand exactly how every medical drug works, so this should not worry us.
This position reveals a deep-seated assumption about the nature of depression and the action of antidepressants, which helps to explain why the myth of the chemical imbalance has been allowed to survive for so long. These psychiatrists assume that depression must be the result of some specific biological processes that we will eventually be able to identify, and that antidepressants must work by targeting these.
These assumptions are neither supported nor helpful. They are not supported because, although there are numerous hypotheses (or speculations) other than the low serotonin theory, no consistent body of research demonstrates any specific biological mechanism underpinning depression that might explain antidepressant action; they are unhelpful because they lead to overly optimistic views about the actions of antidepressants that cause their benefits to be over-stated and their adverse effects to be dismissed.
Depression is not the same as pain or other bodily symptoms. While biology is involved in all human activity and experience, it is not self-evident that manipulating the brain with drugs is the most useful level at which to deal with emotions. This may be something akin to soldering the hard drive to fix a problem with the software. We normally think of moods and emotions as being personal reactions to the things going on in our lives, which are shaped by our individual history and predispositions (including our genes), and are intimately related to our personal values and inclinations. Therefore we explain emotions in terms of the circumstances that provoke them and the personality of the individual. To over-ride this common-sense understanding and claim that diagnosed depression is something different requires an established body of evidence, not an assortment of possible theories.
Models of drug action
The idea that psychiatric drugs might work by reversing an underlying brain abnormality is what I have called the ‘disease-centred’ model of drug action. It was first proposed in the 1960s when the serotonin theory of depression and other similar theories were advanced. Before this, drugs were implicitly understood to work differently, in what I have called a ‘drug-centred’ model of drug action. In the early 20th century, it was recognised that drugs prescribed to people with mental disorders produce alterations to normal mental processes and states of consciousness, which are superimposed onto the individual’s pre-existing thoughts and feelings. This is much the same as we understand the effects of alcohol and other recreational drugs. We recognise that these can temporarily over-ride unpleasant feelings. Although many psychiatric drugs, including antidepressants, are not enjoyable to take like alcohol, they do produce more or less subtle mental alterations that are relevant to their use.
This is different from how drugs work in the rest of medicine. Although only a minority of medical drugs target the ultimate underlying cause of a disease, they work by targeting the physiological processes that produce the symptoms of a condition in a disease-centred way.
Painkillers, for example, work by targeting the underlying biological mechanisms that produce pain. But opiate painkillers may work in a drug-centred way too, because, unlike other painkillers, they have mind-altering properties. One of their effects is to numb emotions, and people who have taken opiates for pain often say they still have some pain, but they do not care about it anymore. In contrast, paracetamol (so often cited by those defending the idea that it does not matter how antidepressants work) does not have mind-altering properties, and therefore although we may not fully understand its mechanism of action, we can safely presume it works on pain mechanisms, because there is no other way for it to work.
Like alcohol and recreational drugs, psychiatric drugs produce general mental alterations that occur in everyone regardless of whether they have mental health problems or not. The alterations produced by antidepressant vary according to the nature of the drug (antidepressants come from many different chemical classes – another indication that they are unlikely to be acting on an underlying mechanism), but include lethargy, restlessness, mental clouding, sexual dysfunction, including loss of libido, and numbing of emotions. This suggests they produce a generalised state of reduced sensitivity and feeling. These alterations will obviously influence how people feel and may explain the slight difference between antidepressants and placebo observed in randomised trials.
In my book, The Myth of the Chemical Cure, I show how this ‘drug-centred’ view of psychiatric drugs was gradually replaced by the disease-centred view during the 1960s and 70s. The older view was erased so completely, that it seemed people simply forgot that psychiatric drugs have mind-changing properties.
This switch did not occur because of scientific evidence. It occurred because psychiatry wanted to present itself as a modern medical enterprise, whose treatments were the same as other medical treatments. From the 1990s, the pharmaceutical industry also started to promote this view, and the two forces combined to insert this idea into the minds of the general public in what has to go down as one of the most successful marketing campaigns in history.
As well as wanting to align with the rest of medicine, in the 1960s the psychiatric profession needed to distance its treatments from the recreational drug scene. Best-selling prescription drugs of the period, amphetamines and barbiturates, were being widely diverted onto the street (the popular ‘purple hearts’ were a mixture of the two). So it was important to emphasise that psychiatric drugs were targeting an underlying disease, and to gloss over how they might be changing people’s ordinary state of mind.
The pharmaceutical industry took up the baton following the benzodiazepine scandal in the late 1980s. At this time it became apparent that benzodiazepines (drugs like Valium- ‘mother’s little helper’) caused physical dependence just like the barbiturates they had replaced. It was also clear they were being doled out by the bucket load to people (mostly women) to medicate away the stresses of life.
So when the pharmaceutical industry developed its next set of misery pills, it needed to present them not as new ways of ‘drowning one’s sorrows’, but as proper medical treatments that worked by rectifying an underlying physical abnormality. So Pharma launched a massive campaign to persuade people that depression was caused by a lack of serotonin that could be corrected by the new SSRI antidepressants. Psychiatric and medical associations helped out, including the message in their information for patients on official websites. Although marketing has died down with most antidepressants no longer on patent, the idea that depression is caused by low serotonin it is still widely disseminated on pharmaceutical websites and doctors are still telling people it is the case (two doctors have said this on national TV and radio in the UK in the last few months).
Neither Pharma nor the psychiatric profession has had any interest in bursting the chemical imbalance bubble. It is quite clear from psychiatrists’ responses to our serotonin paper that the profession wishes people to continue under the misapprehension that mental disorders such as depression have been shown to be biological conditions that can be treated with drugs that target the underlying mechanisms. We haven’t worked out what those mechanisms are yet, they admit, but we have plenty of research that suggests this or that possibility. They do not want to contemplate that there might be other explanations for what drugs like antidepressants are actually doing, and they do not want the public to do so either.
And there is good reason for this. Millions of people are now taking antidepressants and the implications of discarding the disease-centred view of their action are profound. If antidepressants are not reversing an underlying imbalance, but we know that they are modifying the serotonin system in some way (though we are not sure how), we have to conclude they are changing our normal brain chemistry – just like recreational drugs do. Some of the mental alterations that result, such as emotional numbing, may bring short-term relief. But when we look at antidepressants in this light we immediately understand that taking them for a long time is probably not a good idea. Although there is little research on the consequences of long-term use, increasing evidence points to the occurrence of withdrawal effects which can be severe and prolonged, and cases of persistent sexual dysfunction.
Replacing the serotonin theory with vague assurances that more complex biological mechanisms can explain drug action only continues the obfuscation, and enables the marketing of other psychiatric drugs on equally spurious grounds. Johns Hopkins, for example, is telling people that ‘untreated depression causes long-term brain damage’ and that ‘esketamine may counteract the harmful effects of depression.’ Quite apart from the damage to people’s mental health by being told they have, or will soon get brain damage, this message encourages the use of a drug with a flimsy evidence base and a worrying adverse effect profile.
The serotonin hypothesis was inspired by the desire of the psychiatric profession to regard its treatments as proper medical treatments and the need of the pharmaceutical industry to distinguish its new drugs from the benzodiazepines that, by the late 1980s, had brought the medicating of misery into disrepute. It exemplifies the way that psychiatric drugs have been misunderstood and misrepresented in the interests of profit and professional status. It is time to let people know not only that the serotonin story was a myth, but that antidepressants change the normal state of the body, brain and mind in ways that may occasionally be experienced as useful, but may be harmful too.
13 thoughts on “How profit and professional interests have misled us about antidepressants”
Basically we need to get to a place that where service user feels in need of assistance there is a discussion between Doctor and service user about what sort of effects the service user requires or wants to try out. And to prescribe medication which is as safe as is possible.
Thank you for your scholarship.
Hi Joanna. I translated and posted it at MIB. A very good txt you wrote. My best regards Fernando
Enviado do meu iPhone
Thanks Fernando! All the best, Joanna
Thank you again for your important work.
At best these drugs are a neurotoxin Psychiatrists don’t even know how consciousness works let alone a bona fide understanding how medicines work on the Brain indeed Psychiatry has been colonised by big pharma and making a quick buck a deep dive into robust research clearly shows the main active ingredient of an anti depressant drug is Placebo see Bessel Van Der Kolk for a daming analysis of where Psychiatry lost its way since DSM-3 prescribe me social connectedness instead any day of the year !
Joanna, another level-headed clear essay on the effects greed and turning a blind eye have on psychiatrists and Pharma. Of all people, psychiatrists should know better: but they are only human, which, of course, is the problem.
Your work together with Robert Whitaker’s and other’s give us hope that at least one part of a corrupt society based on ‘gain and fame’ might change for the better and cause less harm.
“If antidepressants are not reversing an underlying imbalance, but we know that they are modifying the serotonin system in some way (though we are not sure how), we have to conclude they are changing our normal brain chemistry – just like recreational drugs do.’
This reminds me of Judith Grisel’s application of Solomon-Corbit’s opponent-process theory and adaptation to recreational drug use in “Never Enough.” (See an article I wrote on this in “Never Enough and Adaptation.”)
I also think that Kuhn’s notion of paradigm helps explain the resistance of adherents to the disease-centered model of drug action giving up their paradigm and acknowledging the truth of a drug-centered paradigm of drug action.
Hello from the UK
What an excellent article, thank you very much. My mother, now no longer alive, took Valium for several years when I was young having been prescribed it by a doctor. She eventually managed to wean herself off it but it was a struggle.
Her issues were ultimately an indirect mental abuse by my father’s mother who did not want to accept my father’s marriage to my mother which she saw as unsuitable. This ultimately caused great trauma to my family. Taking pills was never going to resolve that.
As regards psychiatrists and big pharma the corruption and greed are appalling. I have looked at various big pharma drugs and their chemistry and as Luke O’Mahoney says they are essentially neuro-toxic and as a consequence pointless if not harmful.
They can be easily identified by the nitrogen atom in the molecular make-up. Suppressing pain is of no benefit as it does not deal with the underlying cause.
There certainly are chemical imbalances in human bodies, but big pharma have no interest in curing people otherwise they undermine their business model.
I have some dealings with psychiatrists in the NHS and my limited experience is they are very ignorant of body chemistry, let alone the complexities of the human mind.
This is an interesting article, but, I take anti depressants and an anti anxiety. If I don’t have them I want to die. I really don’t care what they do to my brain. I feel better on them and want to be happy.
The perceived slight benifit of taking or being prescribed anti depressants may also be linked with the ability to receive certain disability benefits and eliviate the worry of having to suport oneself whilst feeling unwell for the recipient.
SSRIs prescribed by chemists?
Primary Care Bulletin – 22 September 2022 (Issue 206) “Dear colleagues,
Today, the agreement for the year 4 and 5 of the Community Pharmacy Contractual Framework 2019 to 2024, the 5-year deal between the Pharmaceutical Services Negotiating Committee, the Department of Health and Social Care and NHS England was announced.
The announcement outlines the new services and the expansion of existing services that pharmacy teams will be able to offer to patients and local communities, demonstrating our commitment to continue to make best use of the expertise and skills of pharmacy teams so that people have greater choice and convenience in how they access health care and advice.
In 2023 we will work with community pharmacy to offer a new contraception management service, take referrals from Urgent and Emergency Care centres, and expand the new medicines service to include anti-depressants. The existing blood pressure check and smoking cessation services will be reviewed to allow delivery by pharmacy technicians.”