Models of drug action

Drugs are frequently prescribed for people with emotional and behavioural problems – problems we currently label as ‘depression,’ ‘schizophrenia,’ ‘bipolar disorder’ and ‘ADHD.’ In trying to understand more fully what these drugs actually do to people, I have formulated two different ‘models’ of drug action: the ‘disease-centred’ model, and the ‘drug-centred’ model. The disease-centred model suggests that psychiatric drugs work because they reverse, or partially reverse, the disease or abnormality that gives rise to the symptoms of a particular psychiatric disorder. Thus ‘antipsychotics’ are thought to help to counteract the biological abnormalities that produce the symptoms of psychosis or schizophrenia, ‘antidepressants’ are thought to act on the biological mechanisms that produce symptoms of depression and ‘anxiolytics’ are believed to act on the biological basis of anxiety. ‘Mood stabilisers’ are thought to correct a pathological process that gives rise to the condition of manic depression (bipolar disorder) or, as is sometimes claimed, to variability of mood more generally.

The disease centred model is borrowed from general medicine and presents drugs through the prism of the disease, disorder or constellation of symptoms the drugs are thought to treat. According to this view, drugs have their effects in a diseased or abnormal nervous system. The important effects of drugs are the ones they exert on the disease process. All other effects are of secondary interest and are referred to as ‘side effects’. An example from medicine, one that is often cited by psychiatrists in an effort to re-inforce the disease centred model, is the use of insulin in diabetes. By replacing the body’s failing supply of the hormone insulin, replacement insulin treatment helps to move the body towards a more normal state.  However, even symptomatic treatments like pain killers act in a disease centred way because they produce their effects by counteracting some of the physiological processes that produce pain.

In contrast, the ‘drug-centred’ model suggests that far from correcting an abnormal state, as the disease model suggests, psychiatric drugs induce an abnormal or altered state. Psychiatric drugs are psychoactive substances, like alcohol and heroin. Psychoactive substances modify the way the brain functions and by doing so produce alterations in thinking, feeling and behaviour. Psychoactive drugs exert their effects in anyone who takes them regardless of whether or not they have a mental condition. Different psychoactive substances produce different effects, however. The drug-centred model suggests that the psychoactive effects produced by some drugs can be useful therapeutically in some situations. They don’t do this in the way the disease-centred model suggests by normalising brain function. They do it by creating an abnormal or altered brain state that suppresses or replaces the manifestations of mental and behavioural problems.


Alternative Models of Drug Action

Disease centred model  Drug centred model
Drugs help correct an abnormal brain state Drugs create an abnormal brain state
Drugs as disease treatments Psychiatric drugs as psychoactive drugs
Therapeutic effects of drugs derived from their effects on an underlying disease process Therapeutic effects derive from the impact of the drug induced state on behavioural and emotional problems
Paradigm: insulin for diabetes Paradigm: alcohol for social anxiety


An accepted example of the drug centred model is the proposed benefits of alcohol in people who experience social phobia or social anxiety. Alcohol helps to reduce social anxiety not because it corrects an underlying biochemical imbalance, but because features of alcohol induced intoxication include relaxation and disinhibition. It is the superimposed state of intoxication itself that helps, not the effects of the drug on a disease mechanism.

Another interesting example is the use of opiate pain killers, such as morphine. Opiates exert a direct ‘disease-centred’ effect by slowing the conduction of messages in the pain nerves, but they also have well-recognised psychoactive effects. They induce a characteristic altered state in which people become emotionally detached or indifferent- sometimes this is referred to as ‘emotional anaesthesia’. People who have taken opiates for pain often say that they still have some pain, but they don’t care about it anymore. This is a ‘drug-centred’ effect in as much as it demonstrates the overlaying of the experience of pain by a drug-induced alteration in emotional experience.

When modern psychiatric drugs were introduced in the 1950s, they were understood according to a drug-centred model. Antipsychotics, for example, which were then known as ‘major tranquilisers,’ were regarded as a special sort of sedative. They were thought to have properties that made them uniquely useful in situations like an acute psychotic episode, because they could slow up thought and dampen emotion without simply inducing sleep, but they were not regarded as a disease-targeting treatment. By the 1970s, however, this view was eclipsed and the disease-centred model of drug action became dominant. Accordingly psychiatric drugs were regarded as specific treatments that worked by targeting an underlying disease or abnormality.  The change is demonstrated most clearly in the way drugs have come to be named and classified. Prior to the 1950s drugs were classified according to the nature of the psychoactive effects they produce. Existing drugs were crudely classified as having either sedative or stimulant effects on the nervous system. After the 1950s, however, drugs came to be named and classified according to the disease or disorder they are thought to treat; antidepressants, antipsychotics and anxiolytics, for example.

The ascendance of the disease-centred model of drug action did not occur because of overwhelming evidence of the superiority and truth of the disease-centred model. There was not then, and is not now, convincing evidence that any class of psychiatric drugs has a disease centred or disease-specific action. There was not even any real debate about alternative theories of drug action. The disease centred model just took over and the drug-centred view simply faded away. People forgot there had ever been another way of understanding how psychiatric drugs might work.

My work has focused on rehabilitating the drug-centred view of drug action because I believe it is the correct way of understanding what the drugs we currently use are doing when they are taken by people diagnosed with mental health problems (and anyone else for that matter). The drug-centred model demands a more thorough understanding of the total range of effects that drugs produce and starts from the point of view that all drugs are foreign chemicals that necessarily change the way the body normally functions. The drug-centred model focuses our attention on the impact that drugs have on the body and the brain, and on all the possible consequences that drug-induced alterations can have on how people think, feel and behave. It is a necessary starting point for the sensible, cautious and safe use of drugs in mental health services.


25 thoughts on “Models of drug action

  1. Thought-provoking post, but not quite clear how you are using the term ‘normal’. What if the ‘way the body normally functions’ is problematic e.g. the person is over-anxious and excessively socially inhibited? Does self-medication using small quantities of alcohol resolve or create problems – or both?

    Also, unclear about how you’re using the term ‘drug’. Human beings ingest a spectrum of ‘foreign chemicals’ including those in what are usually classified as foodstuffs, which have a range of effects on the body and which change the way it ‘normally’ functions – if you’re intolerant of particular proteins, you can have a serious problem with a food that most people eat with no ill-effects.

    • Good points. Alcohol generally relaxes people, so people who are feeling excessively anxious, stressed and tense may exeprience it as helpful. The point is that it is not reversing the anxiety mechanism, but producing its own artifical state of relaxation. Using alcohol to aid relaxation is neither a good or a bad thing in itself. It depends on how often, how heavily and how continuously it is used, whether it stops the person developing other, more generalisable coping mechanisms etc. Another example might help. Some people turn to opiates like heroin to dull the emotional pain of a traumatic childhood. Opiates do not reverse the negative emotions such people experience, they superimpose their characteristic state of emotional detachment or numbness. I am not making any comment here about whether this way of using substances is good or bad. I am simply trying to clarify the way that psychoactive substances may interact with emotions.

      A drug is a substance that is not normally present in the body but that interacts with the body’s physiological processes when ingested (as opposed to an inert substance that does not). Foodstuffs are a normal part of the body’s physiological processes.

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  3. Thanks for responding Joanna. I think the entire issue is made more problematic than need be (and emotional and behavioural difficulties are already complex enough) because of the way the issues are categorised. Much of the categorisation used in ‘mental health’ is dichotomous (mental/physical, healthy/sick, ‘medical condition’/no ‘condition’ ) when much of the natural world isn’t like that.

    Although the points you make in your post about the differences between a disease-centred model and a drug-centred are important, I feel your model is itself marred by dichotomous categorisation. My main concern is about the distinction you make between ‘normal’ and ‘abnormal’.

    As far as I’m aware, medical science on the whole recognises that ‘normal’ includes variation – hence reference ranges. It also recognises that someone with a particular physiological function within the normal range can nonetheless be ill because of it, or someone with a function outside the normal range can be perfectly healthy. In short, normal/abnormal is not seen as a dichotomy, but as a range.

    Ranges also apply to other things, such as what human bodies ingest. Ingested substances can vary in their effects from being inert at one end of the spectrum through being mainly nutritious, to having mainly negative effects, through to fatal toxicity at the other extreme.

    The interaction between the range of properties of ingested substances and the range of physiologies of individuals means that what one person’s body uses as a source of nutrients can produce strongly adverse effects in another person’s. So I’m not clear exactly what you mean by ‘normal’.

    Your categorisation of ingested substances appears to be more categorical: inert substances (that have no effect on anyone); foods (despite human beings having intolerancies or allergies to a number of proteins); medicines (that counteract disease processes), drugs (that overlay ‘normal’ processes rather than counteract disease processes); and presumably toxins (substances that are toxic to everybody).

    I’m also unclear about your models of biological mechanisms. Pain, for example, generally has three main components; the cause that triggers the pain, the pain signal mechanism, and a perceived sensation. If I’m in pain, my first preference would be to remove what’s causing it. My second would be to counteract the pain signal mechanism. If neither of those were an option, I’d go for anything that stopped me perceiving the pain. The latter, although it doesn’t address any causes, can be enormously helpful because it can allow me to take whatever steps are needed to address the causes.

    Although I take your point about there being a shift from psychiatric drugs being seen as a stimulants or sedatives that didn’t counteract a disease process, to them being seen as counteracting a supposed disease process, there has also been a shift in the nature of psychiatric drugs. SSRIs, for example, as far as I’m aware, do reduce the re-uptake of serotonin. So if low serotonin levels are a problem, SSRIs are likely to help in that respect because they do counteract the disease process. This is a different issue to making an assumption that low serotonin is a problem, or that it’s the cause of the problem, but making that assumption doesn’t affect the validity of SSRIs as part of a disease-centred model.

    I think I might reply on my blog, because there were a number of other points in your post that made me think ‘Yes, but…’

  4. Your comments illustrate why the models I have formulated are important. The point is that there is no evidence that any drug currently used for mental health problems has a disease centred mechanism of action. The psychoactive effects these drugs induce are sufficient to account for the effects they are observed to have in randomised trials and other studies. You may dislike dichotomous models, and like the idea that drugs might do a ‘bit of this and a bit of that,’ but the fact is that no psychiatric drug has yet been shown to address any (hypothetical) underlying mechanism.

    You are right that ‘normality’ is not easy to define, but there are physiological norms, and we can characterise what drugs do by how they alter these. Thus stimulants increase the heart rate above what it would be without stimulants, and drugs like neuroleptics reduce the activity of dopamine below what it would usually be.

    I think you may be under the impression that there is evidence for underlying mechanisms in some mental disorders, when in fact there is not. SSRIs do elevate serotonin in the short-term, although we don’t know what effects they have with long-term use. There is no evidence that depression is caused by low serotonin, however. I have critiqued the evidence that has been put forward for the serotonin theory of depression in detail in The Myth of the Chemical Cure, and briefly elsewhere (, but I don’t think anyone would claim any longer that depression is caused by a serotonin deficiency. Two American researchers wrote an interesting article about the ‘evidence gap’ between what was frequently claimed in the media, and what experts actually say on this issue (

    The Eli Lilly scientist who developed Prozac acknowledged in a recent BBC programme that they had no idea how Prozac actually worked.

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  6. Thanks for further comments, Joanna.

    A few points:

    1. It’s not that I ‘dislike’ dichotomous models; it’s that given the variation inherent in biological organisms, they are generally unhelpful when categorising biological phenomena. Biological ‘normality’ isn’t just difficult to define, it doesn’t actually exist other than in prototypical features which can’t always be applied to individuals.

    2. You mentioned physiological norms. In fact the ‘norms’ are not ‘norms’ at all, they are reference ranges – the limits of which are the levels of physiological functions seen in 95% or 97.5% (or whatever percentage is deemed most useful) of a given population. Doctors are quite familiar with issues such as a patient with a test result within the reference range but that’s abnormal and pathological for that individual; a patient who is perfectly healthy but has a test result outside the reference range; and patients whose levels of a particular physiological function dip in and out of the reference range.

    3.Drug effects at the populations and individual levels are not the same. As I’m sure you’ll agree, a construct like ‘depression’ or ‘anxiety’ is highly likely to be heterogeneous – even if there’s complete agreement that a particular group of people all feel ‘depressed’, it doesn’t mean that they all share the same cause or mechanism for their depression. If the depression of some of the group is caused by low levels of serotonin it’s very likely that an SSRI might stop them feeling depressed. If their depression doesn’t have this cause, then an SSRI won’t do the trick.

    The only things an RCT is likely to tell you about a treatment for a condition that’s likely to be heterogeneous are a) that the condition is heterogeneous, and b) whether or not the treatment is effective for a sub-group. If it is effective for a sub-group, then it’s as inappropriate to dismiss it as a treatment for anybody as it is to promote it as a treatment for everybody.

    4. It’s important to keep distinct issues distinct. The disease model of ‘mental illness’, presenting the serotonin deficiency hypothesis as a fact, doctors’ and patients’ assumptions, side effects of drugs and the inappropriate promotion of drugs as treatments for so-called ‘mental disorders’ are distinct issues and although in this case they are related, they’re not all part and parcel of the same thing.

    For example, the history of medicine is littered with treatments and procedures that were found to ‘work’ before anyone knew why they worked; surgeons anointing the patient with alcohol before operating and ostlers feeding mouldy apples to sick horses spring to mind. Just because a hypothesis is a hypothesis doesn’t mean it’s wrong.

    5. You’re right, I am under the impression that there is evidence for underlying mechanisms in some mental disorders. We’re biological organisms. Whatever the root cause, our thinking, feeling and behaving must have underlying mechanisms or we wouldn’t be thinking, feeling or behaving. It doesn’t follow that dealing with problematic thinking, feeling or behaving should target a putative mechanism.

    But ‘evidence’ isn’t a black-or-white thing. Evidence can vary between being as close to conclusive as you can get, to vaguely pointing in a particular direction. Since neurotransmitters are inextricably linked to thinking, feeling and behaving, whatever the root cause, it would be astonishing if they weren’t somehow involved in so-called mental disorders. It doesn’t follow, however, that popular conceptions of mental disorders are correct nor that targeting neurotransmitters constitutes an appropriate treatment for them.

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  22. I am currently taking a society and mental illness class for college. My professor asked us to answer the following: “Compare and contrast disease-centered and drug-centered models of psychiatric drug action. Imagine that you are considering starting a course of psychiatric drug treatment. What are some implications of the disease-centered vs. drug-centered distinction to you?”

    We were assigned the “Rethinking Models of Psychotropic Drug Action” article but I was ultimately able to find this page. I find your work to be very interesting, however, it is very hard to understand the article as a introductory psych student. I did feel like I was able to better understand the entirety of the issue after reading this page though. I think its very important for introductory students to be able to read and understand articles like this without having to follow up on them and just thought I would share my opinion with you about that. Otherwise, your work is very informative and interesting. I appreciate learning alternative views about pretty much anything, so great job!

    My thoughts on Logicalincrementalism: It is truly disheartening to have to always read comments that try and pick apart another persons hard work. If you have nothing better to do, try doing your own research. Do something productive with all of your knowledge and wisdom.

    • Dear Jessica,
      thanks for your comments. I am sorry the paper was not more self-explanatory. One of the problems was trying to explain the ideas and provide all the evidence in a short paper. I am glad that the material here has made the subject clearer. Can I ask what college you are studying at? I am intersted in where my work is being discussed. Good luck in your essay! Joanna

  23. with regards Anti-NMDA receptor encephalitis inducing psychosis, the question people should be asking is: do psychiatric drugs and/or other drugs provoke an autoimmune response to the NMDA receptor because of the imbalance – caused by the drugs – as part of the bodies response to correct itself ?

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