Mental Health Act reform by a failed government

The Government has responded to the Joint Committee on the draft Mental Health Bill (see previous post). Tim Spencer-Lane has summarised in a Linkedin post which recommendations from the Scrutiny Committee were rejected and which were accepted by the government. As I said in a tweet, the response is disappointing but not surprising. As I keep saying, current reforms of the Mental Health Act (MHA) do not go far enough (see previous post). I also think that the opportunity should be taken to reform the Mental Health Tribunal (see another previous post) and formalise the role of a triage AMHP (see yet another previous post).

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). 

Habituation to antidepressants

Discussion on the Critical Psychiatry Network email list has firmed up my views about antidepressant withdrawal. As I point out on my Antidepressant Discontinuation Reactions webpage, there is confusion about the technical meanings of terms like drug dependence and drug addiction. Dependence and addiction in common parlance, though, tend to mean difficulty in managing without the drug. This is a psychological problem, and can also have a physical cause.

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.

The problem with benzodiazepines is why the antidepressant market was so worried about also being labelled as causing physical dependence and went for admitting antidepressant discontinuation problems. Paxil/Seroxat makers, seen as being the worse for causing discontinuation, but I think probably unfairly because the fluoxetine people wanted to turn the focus away from themselves by pointing out the longer half-life, also had to admit that it caused addiction because of the common parlance use of the word (see Guardian article). The old common sense distinction between physical and psychological dependence got fudged by the syndromal approach of Edwards et al, even though there was strength in the syndromal approach with its seven elements (see Edwards & Gross (1976)).

Does anyone these days even know what I’m talking about when I say the syndromal approach to alcoholism and drug dependence? As I keep saying, psychological factors in antidepressant withdrawal cannot be denied. I’m just encouraging a sceptical attitude about physical withdrawal.

The truth about ADHD

The Times has an article about ADHD but does not make clear that that there is no evidence that ADHD is a neurodevelopmental condition affecting the prefrontal cortex of the brain, which is what the article says is the case. Nor does it really make sense to say that ADHD is executive brain dysfunction (see previous post). These types of misunderstanding that ADHD is a brain disorder pervade public consciousness, even though they are wrong. 

The Times article quotes the consultant psychiatrist apparently behind the website Parenting Matters as saying there is no increase in actual instances of ADHD, which is misleading at least, if not wrong. He apparently thinks the real problem is just worry about ADHD. The difficulty with that explanation is that it denies that there is any overdiagnosis of ADHD. If there is no overdiagnosis why do numbers of cases continue to rise? At least the article correctly states that there is no blood test for neurodiversity.

Nor does an ADHD diagnosis necessarily mean treatment with Ritalin is required. Anyway, Ritalin does not always work (see previous post). If it ‘works’ it could just be because of the placebo effect. There is no evidence that amphetamine (Ritalin) particularly affects the brain chemical noradrenaline in those with ADHD to produce a paradoxical calming and focusing effect, rather than hyperactivity. Again, these common misunderstandings are widespread.

Last year a Panorama investigation uncovered rogue psychiatrists misdiagnosing ADHD, shining a light on the very real market for a diagnosis (see previous post). This exploitation of people occurs maybe particularly obviously online (see another previous post). Society does need to adapt to individual differences between people, but that doesn’t necessarily mean that increasing the diagnosis of ADHD and other neurodevelopmental diagnoses is the answer to understanding and managing our differences from each other (see yet another previous post).

My BMJ article described how the identifying of behaviour of children when stressed as ADHD can avoid having to deal with the difficult task of improving family and school life. For example, is ADHD an excuse for misbehaviour in schools? Looked at in this way, it is indeed likely that recourse to drug treatment discourages self responsibility and thereby exacerbates the underlying difficulties that it is supposed to remedy. As far as the diagnosis of ADHD in adults is concerned, many psychiatrists think this is an example of the over-medicalisation of everyday life (see previous post).

There needs to be a much more open debate about the societal diagnosis of ADHD. 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).

Placebo effect is responsible for antidepressant improvement in clinical trials

Peter Simons has an excellent blog post on Mad in the UK. He makes the case that the apparent benefit of antidepressants in clinical trials is an artefact and that any apparent improvement in depression is due to the placebo effect, not any active effect of the antidepressant.

The effectiveness of treatment is assessed in randomised controlled trials comparing active drug with placebo (see my OpenMind article). Participants are randomly assigned to two groups in the basic design,  in which they are given either the active drug or given a placebo, which is supposed to be inert and indistinguishable from the active drug. In other words, participants should not know to which group they have been allocated, so that they are blinded to which allocation they have been given. This is important as if they did know whether they had been given active drug or placebo then their expectation of the implication of that allocation could affect outcome. If they think, for example, the drug being tested is likely to be effective, then merely knowing the allocation may produce or exaggerate any difference between the two groups. If there is a significant difference between the groups, the finding may merely be a self-fulfilling prophecy that the active drug is better than placebo.

As Justin Karter said in a recent Mad in America blog post, an individual’s subjective belief about receiving active or placebo treatment in a clinical trial can significantly influence the outcome of treatment. If participants are unblinded, or unmasked - another word for unblinded - as to which treatment they have received, then these expectations could still be affecting outcome. Justin reviews a paper by Fassi et al (2023) that demonstrated in neurostimulation studies (see eg. previous post about neurostimulation) that the belief of receiving the active or the placebo condition during a trial can explain the research outcome better than the actual treatment to which the participants are assigned. In other words, the individual differences in subjective treatment explained the variability in outcomes better than the objective treatment.

I participated in a BMJ rapid response discussion following what I think is the most definitive paper about whether trials should obtain data about participants’ guesses as to which treatment they were given at the beginning of a trial. As explained above, trials are expected to be blinded/masked, so that neither patients or doctors, including raters, do not know whether participants are in the treatment or placebo group. As I also said in my last contribution to that rapid response discussion, there is a general positive gloss put on the problem of unblinding/unmasking in clinical trials. I went on:-

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).