Thursday, April 11, 2024
Rethinking mental health practice
Rethinking neurodiversity
Neurodiversity is the term used to describe the wide variety [of] different ways human beings think, learn, communicate and exist in the world. It is an umbrella term - a word that sums up lots of different things and helps us reframe conditions such as autism, ADHD, dyslexia as differences rather than deficits.
As I mentioned in my last post, a recent report on autism in children and young people, one of the main components of said neurodiversity (see previous post), by the N8 Research Partnership talks about the need for a radical rethink on autism. It was the result of a collaborative programme of work between Child of the North and the Centre for Young Lives. Three helpful evidenced-based recommendations are made:-
(1) Build effective partnerships between education and health professionals for assessing and supporting autistic children. This should include delivering assessments in education settings and making a holistic offer of support in schools and nurseries before and after a formal diagnosis is made.
(2) Provide and extend access to mandatory Continuing Professional Development (CPD) courses for health, education, and social care professionals that improve understanding and awareness of autism (and related issues). These courses should include information on how to create “neurodiverse friendly” environments, and particularly raise awareness of autism in girls and ethnic minority groups. Additional training should be co-produced by individuals with lived experience, delivered to professionals, and integrated into undergraduate health and education professional training, to improve the identification of autistic girls.
(3) Create formal partnerships at a local authority level comprising sector leaders (including schools, health, voluntary services, faith, universities, educational psychologists, and businesses) to oversee a prioritised governmental ward-level approach to addressing the autism crisis. The partnership should focus on its most disadvantaged wards and provide leadership in trialling data-driven, community and family co-produced, “whole system” approaches to improve autism support with and through education settings.
As the report says, these recommendations have resource implications but offer the potential for decreasing long-term costs by acting now. They should actually benefit the economy by increasing the employment of autistic people. Throwing money at the problem doesn’t solve it. To quote from the report:-
The time has come for everyone to cross organisational and geographical boundaries and commit to working together in the best interests of autistic CYP [children and young people] and their families.
A major barrier to progress is the overemphasis on psychiatric diagnosis (see eg. my article). This relates to the overmedicalisation of developmental and mental health problems (see eg. previous post). I very much agree with the essence of the report that support should be given on the basis of need regardless of the diagnosis of autism.
Monday, April 08, 2024
The industrialisation of neurodiversity
Neurodiversity has become an industry, often more motivated by profit than patient interest. Biomedical myths that suggest emotional problems are due to brain disorder support this development, although the neurodiversity movement itself promotes neurodiversity as not being a mental health problem. Neurodiversity in this sense means intrinsic diversity of brain function (see previous post). Society does need to adapt to individual differences but to suggest these personal differences are due to brain problems is also a biomedical myth.
The internet does seem to have made it relatively easy to sell all sorts of mental health treatments online, including psychological, medication and other physical treatments (see eg. previous post). People talk about COVID causing an increase in demand for mental health treatments, but maybe that’s just because the pandemic was associated with more widespread use of the internet. In another previous post, I expressed scepticism that COVID really increased depression and anxiety, not to minimise the emotional impact of the pandemic, and of course long COVID. Certainly, as I said in my last post, the marketing of digital apps online is out of control. And it’s particularly the diagnosis-led basis of such interventions than can lead to their exploitation, even to corrupt business practices (see eg. yet another previous post).
As I keep saying, the cultural process of seeking to create panaceas for emotional and other mental health problems doesn’t always work and may create more problems than it is worth (see previous post). The limitation of treatment to help people cope with their differences from others does need to be recognised, but such people should be able to obtain support if they ask for it. They don’t necessarily require a label of neurodiversity or any other mental health diagnosis to be able to make the most of that support.
Tuesday, April 02, 2024
Digital apps in mental health
What's needed is better evidence that these apps are of any benefit to people. Placebo effects need to be controlled in research studies. As Charlotte says, many studies lack a clear description of the nature of the control. Robust placebo design is required in randomised controlled studies. As with psychotherapy trials there will always be a question in assessing the efficacy of mental health apps about the adequacy of control groups (see my BMJ letter). There is enough questioning even of the effectiveness of psychotropic medication (see eg. another previous post) and psychotherapy (see eg. yet another previous post) to reinforce the need to ensure that these apps are not really exploiting people.
There is concern, of course, in general about misinformation on the internet (see eg. previous post). But medication and other physical treatments for mental health problems and psychological therapy are being oversold on the internet (see eg. another previous post). How are we supposed to decide which is the best app to use? Does it matter? Are they just panaceas (see yet another previous post)? I'm not saying using a digital app may not help. But we do need to recognise their limitations and potential costs and side effects.
Monday, March 25, 2024
Mental Health Act reform by a failed government
Failure to follow the recommendation about abolishing community treatment orders (CTOs) for civil patients is the most serious issue. What was fudged by the original review led by Simon Wessely was that mental health legislation is about supporting people with mental health problems (see previous post). Instead the government continues to parrot that review by saying that the MHA "governs the compulsory detention and medical treatment of people with severe mental illness, people with a learning disability and autistic people". It does but it also does, or should do, far more than that.
Increasing coercion, such as CTOs, is not always the best way to manage risk in mental health services. The over-preoccupation with risk, that led to the introduction of CTOs, has not always produced sensible risk management (see previous post). Even more fundamentally, rights and recovery-orientated services need to be at the centre not the margins of mental health services (see another previous post), whereas the government merely says it will keep a rights-based approach under review (see response to recommendation 2 from the Scrutiny Committee). The government does not seem to be taking seriously that system and service changes are required to reduce coercion in mental health services as recommended by both the World Health Organisation and World Psychiatric Association (see yet another previous post).
The Scrutiny Committee's recommendation for the creation of a MHA Commissioner, rejected by the government, was also helpful. As I said in a previous post, taking over the function of the Mental Health Act Commission (MHAC) by the Care Quality Commission (CQC) has meant, in my view, that a "specific emphasis on the rights of detained patients has been lost, as CQC has the more general role of regulating health and social care". More independence from CQC and NHS England is required to protect the rights of mentally ill people, as reflected in recent scandals exposed by TV programmes like Panorama (see eg. another previous post). The criteria in mental health legislation that allow coercive treatment are too wide to prevent abuse (see yet another previous post) and this must be remedied.
Not sure if the publication of this government response to the scrutiny committee will be taken forward in this parliament, such as having parliamentary time to discuss it. I think any Labour government will have to ask DHSC to go back to first principles, although there are many proposals, both within current draft legislation and elsewhere, including on this blog, which can be taken forward on this basis (see previous post).
Saturday, March 09, 2024
Habituation to antidepressants
As I also say in a previous post, The National Institute for Health and Care Excellence (NICE) clearly states that antidepressants cause withdrawal symptoms even though they have not historically been classified as dependence-forming medicines. It sees dependence as characterised by tolerance and withdrawal symptoms. Addiction is said to include the additional characteristics of cravings, lack of control, overuse and continued use despite harm, associated with problematic behaviours.
People can become habituated to antidepressants. As I wrote in my OpenMind article :-
People may form attachments to their medications more because of what they mean to them than what they do. Psychiatric patients often stay on medications, maybe several at once, even though their actual benefit is questionable. Any change threatens an equilibrium related to a complex set of meanings that their medications have acquired.
Taking antidepressants can be an identity-altering experience (see previous post). No wonder people can have difficulties discontinuing them. People can be frightened about stopping antidepressants (see another previous post and yet another previous post).
Probably the first systematic review of antidepressant withdrawal was by Fava et al (2015) (see previous post). Personally, like Fava et al, I’ve always emphasised the vulnerability to relapse created by taking antidepressants (see another previous post). I’ve encouraged a focus on psychological aspects of prescribed drug dependence (see eg. my book chapter). Critical psychiatrists who believe in deprescribing often think the evidence for physical dependence is incontrovertible. But I do not agree.
There is little evidence that antidepressants cause increased tolerance, for example, in the same way as alcohol and opiates. Antidepressants are not primarily reinforcing like psychostimulants (see eg. previous post). I, therefore, think it is a mistake to say that antidepressants cause physical dependence. That’s not to diminish the power of psychological dependence, which they do cause.
Functional somatic symptoms caused by antidepressant withdrawal are of course common in medicine. It’s the nature of such symptoms that people find it difficult to appreciate they may not have a physical cause. Hence people who have experienced antidepressant withdrawal often disagree with me, sometimes vehemently. Nonetheless, the commonsense view is that people can become dependent on antidepressants for psychological reasons. This was a finding from the Defeat Depression campaign when it tried to educate the public that antidepressants are not addictive, when commonsense understanding is that they must be in the common parlance definition of addiction, as above, as the public already knew (see my BMJ letter).As I note on my Antidepressant Discontinuation Reactions webpage, the strongest evidence in favour of physical dependence is neonatal withdrawal reactions. I note there, though, that data from spontaneous reporting is difficult to interpret. I haven’t updated that webpage for some time, but even so, neonatal reactions could be due to serotonin syndrome rather than withdrawal. It worries me about the dose of antidepressants that is getting through to neonates in utero. As far as I can see, the more recent studies of poor neonatal adaptation after antidepressant exposure in third trimester have not been able to distinguish that the cause is withdrawal rather than serotoninergic toxicity.
I’m old enough to remember the debate about whether withdrawal symptoms in benzodiazepines were merely due to habituation or physical dependence, led by someone like Malcolm Lader, who in the end came down on side of physical dependence, but he would never have denied psychological dependence. It is true that what led to the decline in the benzodiazepine market was the claim that benzodiazepines cause physical dependence, which I agree there is evidence for because of convulsions on withdrawal. Still, even with most physically dependence forming substance there is also psychological dependence and this must not be denied.
Friday, March 08, 2024
The truth about ADHD
Placebo effect is responsible for antidepressant improvement in clinical trials
The general thought seems to be that measuring unblinding is difficult, so we may as well give up and carry on with our pretence [that trials are blinded]. This may be to continue "turning a blind eye", as used in the phrase in the title of the original paper.
I suggested:-
I think it may be possible to measure what the degree of unblinding should be from correct hunches from efficacy based on effect size, and if the actual degree of unblinding with correct guesses is significantly greater than this, it would surely imply that bias had been introduced. … I am reluctant to … be as negative about the implications [of measuring unblinding/unmasking] as some of my fellow rapid responders.
I emphasised that in clinical trials that it is the raters that can detect unblinding, not just participants and that raters guesses matter even more than patient guesses, certainly if those patient guesses are not directly communicated to the rater when the assessment by the rater is undertaken.
I concluded:-
If raters are able to be cued in to whether patients are receiving active or placebo treatment, their wish fulfilling expectancies could be affecting outcome ratings. How do we know that small effect sizes [as in antidepressant trials, for example] in particular are not due to this amplified placebo effect? I think we should stop turning a blind eye to this legitimate question. It does need to be answered to give confidence about the use of many medications that are endorsed in clinical practice.
Thankfully, the article by Jureidini et al (2023) reviewed by Peter Simons in his blog post did produce data on unblinding/unmasking in the treatment for adolescents with depression (TADS) study - see my BMJ letter. As I say in that BMJ letter, “Fluoxetine was not in fact statistically better than placebo in this study and only became so when added to cognitive behaviour therapy in an unblinded arm”. It’s therefore wrong to conclusively conclude, as do many people, that the TADS study demonstrated that antidepressants, or at least fluoxetine, improve depression.
There were four treatment arms in the TADS study, which included fluoxetine (Prozac) only; cognitive-behavioral therapy (CBT) only; fluoxetine and CBT; and placebo. In psychotherapy trials it is not possible to blind participants as to whether they are given psychotherapy, such as CBT, from whether they were in the control treatment (see my BMJ letter). They have to be told which group they are in, unless they are deceived about the nature of the trial, which is generally regarded as unethical to do. So it has to be explained to participants that they will be allocated to the experimental therapy in the active condition, or allocated to a control group, which could merely be being put on a waiting list. Obviously they might be hoping that they would be allocated the psychotherapy treatment, rather than continuing on the waiting list for treatment, and are likely to be disappointed if not given that allocation, which could well affect how they rate their degree of improvement or otherwise during the trial. Anyway, psychotherapy trials cannot be conducted double blind and there is always the methodological issue of the adequacy of control groups in clinical trials of such treatment in terms of being able to interpret the effectiveness of psychotherapy.
All four groups in the TADS study guessed treatment allocation more accurately than the 50% that would be expected by chance. Treatment guess had a substantial and statistically significant effect on outcome. The treatment effect was actually then not significant, even though it wasn’t anyway. Removing guesses from the analysis still did not make the treatment effect really significant (p=0.06, when standardly p<0.05 is the significance level used in clinical trials). As Jureidini et al conclude for the TADS study, “treatment guesses strongly predicted outcomes and may have led to the exaggeration of drug effectiveness in the absence of actual effects”. Unblinding, which amplifies the placebo effect, may well be the reason for the small difference in clinical trials between antidepressants and placebo.
Participants in TADS improved more if they believed they had received the drug rather than placebo. Those that guessed placebo even though they had received fluoxetine actually improved more than those on the drug who guessed correctly. Although this was reversed for those that received placebo ie. that those who guessed correctly when on placebo did worse than those actually on the drug, these findings merely highlight the importance of belief about treatment rather than necessarily the treatment itself in outcome of treatment for depression. In fact, those who were more confident of their guess reinforced this effect more than those who were less confident.
Interestingly, Jureidini et al did not find much association with side effects of medication as the reason for unblinding. This has been the typical reasoning of Irving Kirsch, for example, that it is side effects of medication that cue people in to their allocation in a clinical trial (see eg. previous post). There is evidence for this hypothesis in that active placebos, which mimic the side effects of the trial drug, generally reduce the effect size. But it’s not the only reason for unmasking in clinical trials, which can even include fraud by the raters, who actually somehow break the blind before they do their assessment. Holding up to the light sealed envelopes which contain the coded allocation of patients, so that the allocation shows through has been highlighted. Anyway, the guesses of trial participants can easily be communicated to raters in the assessment interview. Participants in antidepressants trials do seem to be significantly unblinded, even if they may not be in lithium trials (see my BJPsych 1996 letter).
TADS should never have been used to recommend fluoxetine for adolescent depression. Analysis of the guesses and subjective beliefs of participants merely reinforces this conclusion and highlights the obvious influence of placebo factors in any response to antidepressants. This placebo effect must not be ignored and the pretence that it has been eliminated in randomised controlled trials must stop. The fear that antidepressants may not be effective and that the modern basis of psychiatric practice in medication may collapse does not justify taking the issue of bias in clinical trials seriously (see eg. previous post).
Friday, February 23, 2024
Independent review following Edenfield scandal
Tuesday, February 20, 2024
Overstatement in the critical narrative of antidepressants
Certainly too much antidepressant prescribing reflects the overmedicalisation of society (see previous post). I think that antidepressants may just be another example of doctors' shameless exploitation of the placebo effect (see another previous post). I also have concern about the misinformation the public are being given about side effects of antidepressants (see yet another previous post).
For example, Jon says that antidepressants are emotionally numbing agents. I’m not sure what he means by this. Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants are generally not very sedative compared to the older tricyclic antidepressants. I agree that antidepressants may prevent people dealing with their problems properly over the longer term. But Jon seems to mean more than this and I’m not clear what he is saying. Certainly people over the longer term report that taking antidepressants often leaves them with a sense of not being themselves (see previous post). They may well say that they experience a flattening of emotional responses. But I don’t think people generally notice that antidepressants on first starting have the physiological effect of emotional numbing, whatever that is.
Of course I’m not denying antidepressants can have a placebo effect. Taking a pill which people are being told improves mood will commonly counteract the demoralisation people generally feel in depression, particularly in those that believe this could be true. As I said, for example, in my OpenMInd article, “Expectation that medication will produce improvement may itself produce apparent benefit”. But, over time, the placebo effect may not last, or may diminish, or may even create other problems, perhaps especially over the very long term. These nocebo, meaning negative placebo, effects also need to be taken into account in assessing the psychological impact of taking medication. Adopting the view that one suffers from a biochemically based emotional illness can be an identity-altering experience (see previous post).
As Jon says, it’s important to emphasise that maybe as many as half of patients stop antidepressants within weeks. Again as Jon says, and here I think he means those that do continue them beyond several weeks, antidepressants should generally be tapered rather than stopped abruptly. Unlike Jon, though, I would say this is only generally the case. How easy people find discontinuing antidepressants can vary considerably. This is not to deny the importance of withdrawal symptoms with antidepressants (see eg. previous post).
I also agree with Jon about the importance of social factors in depression, although how depressing people find being poor, for example, does vary considerably. My final quibble is about Jon suggesting overprescribing is symptomatic of the medicalisation of distress. Actually, as I’ve already said, I agree overprescribing is a symptom of the overmedicalisation of distress. But the problem is too much medicine, not medicine itself. Psychiatry needs to be far more psychosocial, rather than biomedical, in its approach to depression and other mental health problems. It needs to stop reducing functional mental illness to brain disease.
Wednesday, January 31, 2024
Formalising role of triage AMHP in new Mental Health Act
The thesis is wide-ranging and provides rich detail. As in the title, it used the method of appreciative inquiry, asking AMHPs to consider their current practice, define the aspects of practice that are most valued, and use that understanding to clarify and validate their practice for the future.
AMHP assessment with doctors usually leads to detention. Indeed, AMHP services are generally structured on arranging joint assessment with doctors as swiftly as possible. As all AMHPs know, though, finding appropriate doctors is not always easy and can take some time, but joint assessment usually takes place on the same day as referral. High likelihood of detention through assessment with doctors doesn’t necessarily align well with the principle of least restriction and maximising the independence of the person.
The concept of assessment was explicitly extended in the research to include the process of information gathering, multi-agency working, and the inclusion of the referred person and their family before the traditional assessment interview with an AMHP and two doctors. As Matt Simpson said in the thesis:-
This S13(1) MHA 1983 decision-making process is an assessment in itself, with AMHPs only involving doctors in an assessment if this process has exhausted all options and detention has become the only viable outcome in the AMHP’s opinion.
Triage AMHPs could be expected to complete an assessment to conclude that either detention appears to be the only viable outcome or that it can be avoided, potentially reducing the numbers of detentions by formalising the process of this stage. AMHPs in the research also advocated for a more formal inclusive and collaborative pathway to assessment with doctors, that shares complexity and explores alternatives to detention. AMHPs need to use their experience to lower the perception of risk if possible and appropriate.
Reducing detention was the original political motivation for the current MHA reforms (see eg. previous post). There are concerns that current proposals do not go far enough (see eg. another previous post and recent post on The Critical AHMP blog - see previous post). Certainly formalising the role of a triage AMHP has not really been considered in the reform process, as far as I know, and it should be, considering it could well reduce the numbers of detentions. There is also scope, I think, for formalising a requirement in the new Act for AMHPs to discuss alternatives to detention with doctors and other professionals involved in the care of the patient before actually assessing the patient with two doctors with a view to detention. This process could share the responsibility for any decision not to proceed with detention by the AMHP.
It may even be worth considering going even further in reform to reduce detention by removing the risk criterion altogether from the criteria for detention under the Act, as has been done in Italy (see previous post). There is a sense in which mental health services need to concentrate on their therapeutic role rather than necessarily be seen as ‘social policeman’, not that I’m denying the inevitable social role of psychiatry. What determines whether someone needs to be detained is that there are mental changes in the person that require urgent therapeutic detention in hospital which the person does not accept. Of course, some of these people will be at risk to themselves or others, but explicitly removing that focus on risk may lead to a better assessment of the need for intervention, at least for civil cases.
The Convention on the Rights of People with Disability (CRPD) makes clear that people with disabilities can only be detained on the same basis (or for the same reasons) as anybody else (see eg. previous post). There are plenty of people without mental disorder who are dangerous, but they are not detained unless arrested for and sentenced after a crime. It does seem non-discriminatory, therefore, to remove the risk criterion in the Mental Health Act. Mental health services do need to move away from their over-preoccupation with risk (see eg. another previous post).
Changes have been made in the criteria for detention in the current proposals, basically about trying to shift the criteria to the serious end of the spectrum of mental disorder, although there is a question about how much difference this will really make in practice, as deciding on seriousness is so subjective. Still, it’s not too late in producing a Bill to consider again completely reviewing the criteria for detention in the context of introducing the formal role of the triage AMHP, who will have to make any application to detain on the basis of these criteria, together with two doctors. It’s not new that detention requires the agreement of all three of AMHP plus two doctors. Strengthening the authority of the AMHP in that process, I think, will be helpful. AMHPs need to learn to see their role more as a safeguard against detention, rather than merely rubber-stamping what two doctors think should happen.
Saturday, January 27, 2024
Unrealistic expectation of risk prediction by mental health services
Tuesday, January 23, 2024
The Critical AMHP blog
AMHP services have had to adapt to an often surreal dysfunctionality in wider mental health services.
National policy demands fewer detentions under the Mental Health Act, not just in the prime case of racialised people, from whom there may be most to learn, but across the board.
Faced with risks AMHPs [and S12 doctors] were trained to shudder at more than understand, uncertainties of resource, intention, outcome, other professionals more concerned to protect themselves than to reach the person, it can feel difficult not to detain under Mental Health Act.
“Call the Doctor…Quick!” Assessing Children under the Mental Health Act. A post by Sarah Raymond with worrying quote:-
The numbers of referrals for Mental Health Act assessments on children steadily but slowly increase year on year
‘Dilemmas, Conundrums, and Quagmires.’ Tracing the Threads of Ethical AMHP Practice. A post by Alan Bristol with the following slightly amended quotes:-
Ethical concerns are not only a pressing issue, but the central issue or foundational concern for wider Approved Mental Health Practitioner (AMHP) practice.
The statutory mental health system is too coercive and potentially anti-therapeutic in its effects, whilst also continually evidencing structurally racist, patriarchal and heteronormative practices.
Another post by John Michell entitled AMHPersonality: Disordered?, about the disadvantages of using detention in the management of personality disorder, with quote:-
Detaining people with ‘personality disorder’ may be unjust, even when refusal to do so may itself feel like an injustice to the person being assessed.
These quotes are necessarily selective but give a flavour of the perspective of The Critical AMHP blog. It deserves to be more widely known.
Sunday, January 21, 2024
Reforming the Mental Health Tribunal
As I have also said (see eg. previous post), the 1959 and 1983 Mental Health Acts were reforming Acts for the rights of people with mental health problems. There is an opportunity to improve the rights of people with mental health problems even further in a new bill. The Mental Health Review Tribunal was originally a standalone body to hear appeals against detention (see eg. Wikipedia entry). Associated with the amendments to the 1983 Act in 2007, the Tribunal merged with the Health and Social Care Chamber of the newly established First-tier Tribunal in 2008. The Tribunal is now called the Mental Health Tribunal, with the ‘Review’ dropped.
Personally I would reinsert the ‘R’ in the acronym and call it the Mental Health Rights Tribunal in a new bill, making explicit its human rights basis. My experience is that the Tribunal now has become bureaucratic and less focused on patients’rights and has become too much of a rubber-stamping exercise of what the Responsible Clinican is doing. The 1983 Act also introduced the safeguard of Second Opinion Approved Doctors (SOADs), but again, as I have said before (see eg. previous post), the SOAD process has become too much of a rubber-stamping exercise. Safeguards introduced by the 1959 and 1983 Acts, such as Tribunals and SOADs, have actually been watered down in my view.
Sarah Markham asked in a Lancet Psychiatry article whether first-tier tribunals for mental health in England are fit for purpose. As she says, there is concern that Tribunals are dominated by clinical input and that human rights are given lower priority, especially the rights to liberty and access to justice. Tribunals should not merely legitimise coercion and limit access to justice. There are questions about risk assessment with the perceived risk of patients generally being deemed of greater importance than the evidenced facts. She expresses the same concern as me that "tribunals are in effect acting as rubber stamps for medical decisions rather than as an objective and robust accountability organisation and effective protection for individuals".
As I said in my submission to the Parliamentary Scutiny Committee, I have no objection to Tribunals being reduced to a single judge. This would mean that they are no longer dominated by the medical member, whose view panels as a whole rarely oppose. The expert witness role that the medical member provides, in my opinion, would be better provided by independent experts within an integrated advocacy service of mental health lawyers, Independent Mental Health Adocates (IMHAs) and independent experts, not just on medical but also on nursing and social matters.
The Parliamentary Scrutiny Committee recommended introduction of pilots for patients to be able to appeal to a slimmed down Mental Health Tribunal about treatment plans. I think there is time before a bill comes back to take this forward to proceed with a full reform of the Tribunal, so that patients can appeal to the Tribunal both on detention and treatment decisions.
Friday, January 19, 2024
Adapting to individual differences
(With thanks to Evgeny Legedin for alerting me to the BBC News article)
Monday, January 15, 2024
Enlightened thinking about psychiatry
Caygill’s introduction and first chapter to his Kant’s dictionary is the best summary of Kant’s life and work that I know. As he says:-
Anyone practising literary or social criticism is contributing to the Kantian tradition: anyone reflecting on the epistemological implications of their work will find themselves doing so within the parameters established by Kant [his emphasis].
The Enlightenment was the age of criticism with the freedom to examine and criticise the institutions of Church and State. The fundamental condition of the possibility for the age of criticism was the ‘freedom to make public use of one’s freedom in all matters’ [Kant’s emphasis]. As I mentioned on my personal blog (see post), the internet now means public critique is no longer totally dependent on the existence of a publisher, as it was in Kant’s time. At least blogging is freely available on Blogger, which I have used extensively, including 15 years of this blog (see previous post)!
I have mentioned Kant several times previously in this critical/relational psychiatry blog. In particular, I make use of his view that the link between mental and physical is an enigma that can never be solved (see eg. previous post). Kant has been proved right, in a way, that function is not as well localised in the brain as we might hope and expect (see eg. another previous post). As taken forward by Foucault (see eg. yet another previous post), modern psychiatry had its origins in the epoch of criticism, as even reason had to submit to reason’s ‘test of free and open examination’. Kant’s Critique of Judgement, in particular, inquires into the conditions of the possibility of judgement itself. Teleological explanation of nature is required rather than a mechanical one. Mechanical explanation cannot explain living beings. There are limits and boundaries to the extent of legitimate knowledge, including about mental illness (see eg. previous post).
Despite criticism of biomedical psychiatry, it retains dominance in the field of mental health. I’ve always said the wish to find a biological basis of mental illness will never completely go away. But, like Kant, criticism needs to continue to be persistent and obstinate in examining the basis of psychiatry’s, and not just biomedical psychiatry’s, knowledge claims and practice. Psychiatry, including its critical version, needs to be self-critical.
Sunday, January 14, 2024
Acetylcholine’s back: Move over dopamine
Side effects of KarXT include constipation, dyspepsia, headache, nausea, vomiting, hypertension, dizziness, gastro-oesophageal reflux and diarrhoea. The gastrointestinal side effects of xanomeline had previously stopped its development as a psychotropic drug. The combination with trospium is designed to reduce frequency and severity of such adverse events.
Schizophrenic symptoms were significantly reduced by KarXT more than placebo after 5 weeks. The study was said to be masked but no measures of unblinding are included in the research report, so it is difficult to assess its bias. If unblinded, it is likely that the fact that this is a new agent, with the hope, therefore, and maybe expectation, that it will be effective could have influenced results. The trial was funded by Karuna Therapeutics, which has other drugs in its pipeline, and has recently been acquired by Bristol Myers Squibb. Already a global pharmaceutical giant, I’m sure KarXT, if successful, will enhance Bristol Myers Squibb’s finances at least over the next decade.
Acetylcholine is a neurotransmitter. It was the first to be discovered as it is secreted by the vagus nerve. There are two main types of receptors: muscarinic and nicotinic. Muscarinic receptors are the main end-receptor in the postganglionic fibres of the parasympathetic nervous system. They are also present in the brain where all five subtypes are expressed.
The dopamine theory of schizophrenia hasn’t stood up for some time (see eg. previous post). Despite some protests that they do not, psychiatrists generally believe that psychotropic medication corrects chemical imbalances in the brain. They’ll adjust without any qualms to thinking that muscarinic receptor agonists modulate dopaminergic, GABAergic, and glutamatergic signaling in schizophrenia. They’ve been waiting for a antipsychotic drug which doesn’t block dopamine D2 receptors for over 70 years, and Karuna Therapeutics has managed to exploit that situation.
I guess tolerability may be more of a problem than Kaul et al make out, but we shall see. As Cipriani et al (2024) point out, there is no data on comparative benefits and harms of KarXT against existing antipsychotics. Data from longer term trials is also awaited. There are also questions about the actual benefit to patients. Still, I suspect enough has already been invested for the weight of Bristol Myers Squibb to see KarXT to market.
Monday, January 08, 2024
Function is not well localised in the brain
At least part of the reason is that the fundamental issue of biomedical psychiatry is more profound than whether phrenology was true. Phrenology was the first doctrine to suggest that cortical functions could be localised. Even though the specific hypothesis that feeling the shape of the skull could detect the relative size of the underlying organs of mental faculties was shown to be false, people have continued to think that brain functions must be localised in the brain at least to some extent. Hence the vast number of false claims that mental illness is due to abnormalities in particular areas of the brain.
There have always been theories of brain function. However, it was not really until the nineteenth century that science seriously considered that the cerebral cortex might be divided into distinct parts responsible for different functions. The cerebral hemispheres consist of a system of sensory and motor centres. But the subjective aspects of brain functions are more obviously part of psychology than neurology. As far as consciousness in general is concerned, it’s actually a category mistake to think it is in the brain (see eg. previous post). The implication is that functional mental illness cannot be reduced to brain disease in principle (see eg. another previous post). More generally, life cannot be explained in terms of mechanical principles of nature (see eg. yet another previous post).
The first cortical localisation that became widely accepted was linking speech to the frontal cortex. Paul Broca associated damage to the frontal cortex with aphasia in 1861. Nine years later Hitzig and Fritsch discovered the dog's cortical motor area from their observations in dogs after a variety of cortical lesions. Friedrich Goltz (1834-1902) was, however, certain that intellect could not be confined to discrete parts of the cerebrum. He rejected physiological reductionism and believed dementia was a function of the whole cerebrum. Sensory and motor functions are localised to some extent but not all human functions are localised in the brain.
The brain lesion literature continued to support the idea that mental illness could be due to pathological changes in higher structures. This led to Moniz being awarded the 1949 Nobel Prize for Medicine or Physiology for his leucotomy procedures. The modern era of psychopharmacology began believing that chlorpromazine caused an equivalent chemical lobotomy. Psychiatry has still not developed from the era of psychopathological structures (see previous post), despite the disaster, for example, of Walter Freeman’s icepick leucotomy (see eg. my OpenMind article and book review).
It suits psychiatry to forget all this history. It continues to fudge the difference between functional and organic mental illness (see eg. previous post). This is despite it learning at least by the beginning of the twentieth century that human function is not as well localised in the brain as we might hope or expect. Nor should it be conceptually (see eg. another previous post). It’s about time psychiatry moved on from its outdated physical model of mental illness.