What are we overlooking? Reviewing current and alternative treatments for psychosis

In Part 1, I looked at the longer-term inefficacy of ‘maintenance treatment’ with antipsychotics, and also at some ‘disappointing’ outcomes for ‘early intervention in psychosis’ (EIP). Part 2 examined, what I take to be, some ill-founded assumptions supporting their continuing employment.

If long-term reliance on treatment with neuroleptic drugs appears increasingly unjustifiable, what can be said about their use in the first instance?

After a look at that question here and keeping in mind some of the issues that evaluations of early intervention have raised, I’ll consider some alternative measures and adaptations services might incorporate into their approach; with the aim of avoiding both those ‘disappointing outcomes’ and the higher rates of morbidity associated with ‘maintenance treatment’.

The case for developing new approaches to research and treatment is compelling. Some parts of my discussion here are more exploratory in nature, while the evidence for other recommendations is already well established.

If I were to sum up briefly my view on EIP, I’d say it has aspects that are good, some that are bad, and others that are ugly:

• the good — psychosocial support can provide practical psychological resources
• the bad — high rates of ‘bycatch’ and misdiagnosis
• the ugly — potential pathway to dependence and chronicity

I’ve previously outlined one way some of the more damaging consequences of psychiatric treatment may come about. The experience for patients can be tortuous when adverse effects from psych drugs are misdiagnosed as symptoms of psychiatric illness. This can often result in their suffering increasing estrangement and loss of agency, as well as causing lasting morbidity through exposure to psychiatric poly-pharmacy.

Shorter-term efficacy of neuroleptics

But mainstream psychiatric practice insists that the use of dopamine receptor blockading neuroleptics for psychosis is indispensable. Let’s give this claim some scrutiny. Just how well founded is it?

Firstly, the drugs are typically judged to ameliorate only, if at all, what are called ‘positive symptoms’ of psychosis and not the ‘negative symptoms’ of affect, or any cognitive impairments. In fact, some leading ‘molecular psychiatrists’, like Oliver D Howes, recognise that the drugs may, in fact, worsen negative symptoms; impairments that may impoverish a person’s quality of life, occupational and social prospects.

Also now recognised by these ‘molecular psychiatrists’, is that some psychoses, such as that putatively associated with Parkinson’s, can improve with a drug that does not block dopamine receptors.* Hence, the causal origin of such cases cannot be said to lie in ‘excess dopamine synthesis’. It follows that many cases of ‘treatment resistant’ first episode psychosis (FEP) will likely also have some other origin.

Nevertheless, the drugs remain the mainstay of treatment. Their ongoing use typically justified by appeal to statistics. For instance, according to a meta-analysis of clinical trial results, twice as many patients improve with antipsychotic treatment as improve with placebo. A finding derived from double-blind randomized control trials (RCTs), the so called ‘gold standard’ for medical research.

However, it is documented that ‘unblinding’ in these trials is common.** And, as discussed in Part 1, many antipsychotic trials’ methodologies are based on keeping one group of patients on their pre-existing drug regime and switching the other group from that to placebo in a very short time-frame. A procedure likely to result in ‘rebound’ psychotic symptoms from abrupt drug withdrawal.

Placebo helps. Why?

But for the sake of argument, let’s take that statistic at face value: twice as many patients improve with antipsychotics compared to placebo. Conversely then, if my grasp of maths is up to anything, half as many improve with placebo as with the drug treatment.

The rate of ‘non-responders’ to the drugs is generally reported to be around 30–35%. This rate of ‘treatment resistance’ seemingly tends to increase over time. For antipsychotic naive FEP patients, perhaps only 20% fall into this bracket. However, 50% or more of those receiving ongoing attention from services for ‘chronic schizophrenia’ may be deemed ‘treatment resistant’. Increasingly poor drug response over time may largely be due to cumulative exposure resulting in dopaminergic supersensitivity; as the brain’s density of dopamine receptors increases — its natural adaptive response to their blockade.

But let’s say that roughly two thirds of those prescribed neuroleptics do ‘respond’. So, roughly half this number, a third of patients will show some improvement when treated with placebo; following the implicit conclusion of that meta-analysis. That is, they improve without taking antipsychotics. This is a significant phenomenon and one that merits serious attention.

Of course, no one suggests using placebo pills in routine clinical practice. Nevertheless, I think it is worthwhile thinking through what might be happening in these cases. My interpretation would be that this is due not to placebo effects as such, but reflects that participants in a research trial should be; receiving appropriate attention in the form of supportive care from professionals, and any support network they may have. Additionally, that they are allowed some period of time, with suitable rest and settings, in which any symptoms or disrupted functioning may, potentially, resolve of their own accord.

It seems likely to me that this one third of patients improve, in the main, due to the generalised benefits of receiving appropriate care, rather than any beliefs about dummy pills they’re taking.

Non-drug based support

Recently, there have been a few feasibility and pilot trials on non-pharmacological interventions, such as cognitive behavioural therapy (CBT), including the Orygen trial I mentioned in Part 1. They have demonstrated:

• Firstly, that deferring antipsychotic treatment can be done safely. Concerns that this would mean extending the ‘duration of untreated psychosis’ (DUP), potentially worsening longer-term outlook were shown to be unwarranted. A separate study in Finland found that immediate use of antipsychotics for FEP actually lead to worse outcomes five years on, than initially withholding their use.
• Secondly, the ‘non-inferiority’ – in terms of both symptom management and social functioning – of more intensive psychosocial interventions compared with neuroleptic based treatment. (More details on these trials in the footnotes below)***

It has to be acknowledged that these trials were very selective, in that their participants were limited to those willing to engage; ‘help seeking’ individuals not showing aggression, suicidality or other behaviours that would tend to exclude them from a trial. But such selectivity is common in antipsychotic trials, where more ‘challenging service users’ tend to be excluded.

These limited pilot and feasibility studies appear to replicate the results of an earlier more comprehensive research project carried out in California in the 1970s. Headed by Lauren Mosher (then lead psychiatrist for the NIMH), the Soteria Project was based on a model of intensive psychosocial support, called ‘being with’, provided in a home-like residential setting. Where patients could be supported to work through their ‘altered experiences’. Soteria demonstrated that recovery was more than possible without the use of neuroleptics, or with their use much reduced.

The approach “was as successful as anti-psychotic drug treatment in reducing psychotic symptoms in 6 weeks”. And resulted in “better 2-year outcomes for patients with newly diagnosed schizophrenia spectrum psychoses,” when compared with hospital based treatment. Patients were generally enthusiastic about its minimal medication approach.

Other projects would take up its model in the US and elsewhere. The professional insights and guidance gained from the experience of these long-running projects shouldn’t be lost.****

Among the advantages of more psychosocially based models, is that a majority of young people will likely prefer to engage with practical psychological input around social functioning, rather than with clinical management of symptoms. Approaches informed by lived experience such as ‘Hearing Voices’ can enable some to come to terms with their ‘symptoms’ and live well with them.

While a minority of patients may be unwilling to partake in ‘talking therapies’ – perhaps due to cultural factors or beliefs about drugs fixing ‘chemical imbalances’ – it is widely acknowledged that rates of ‘non-compliance’ with ongoing drug treatment are high; due to the drugs’ many adverse effects.

Psychosocially focused interventions may foster better engagement. A more collaborative approach, with greater scope for the client’s self-determination about their care, is more likely to build trust than the coercive approach services often take.

Ensuring that the benefits of psychosocially based approaches can be provided to a less selective group of patients would be a practical challenge. But could revolve around an individual’s progress over time and potential adaptations to existing service models. There are plenty of possibilities already established as both safe and effective. Five decades on from the first Soteria project, I believe its model can be taken and improved upon.

Biomedical approaches: Being wary, but open minded

There are, apparently, new drug treatments in development and said to be promising. Revolutionary new approaches are occasionally touted in the media, but then nothing seems to come of them. I can’t rule out that newer drugs may be better — which is to say, less bad — than neuroleptics. But as I argued in Part 2, drug interventions targeting a single aspect of the brain’s function are likely addressing only one aspect of a multifaceted causality that plays out through functional level network effects, not identifiable with molecular processes.

Given the current level of neuroscientific understanding of causality in the brain and nervous system, it seems pretty much inevitable that exposure to pharmaceutical psychotropics will produce adverse consequences. Even if the harms are not properly recognized or understood till decades later.

I concluded before that assumptions of ‘underlying illness’ are unwarranted, in as much as these assume a single disease process. We are probably talking about multiple aetiologies; arising from a patchwork of susceptibilities, both innate and acquired, and likely triggered by the presence of external stressors — where a person’s conscious interpretation and ‘window on the world’ also play determinative roles. These latter are clearly not reducible to biochemical processes.

Working with a framework like this can, I think, help remove some of the mystery around the typical course of ‘relapse and remission’ that a simple disease model of ‘schizophrenia’ does little to explain.

If the causality cannot be taken as simple, then it stands to reason that interventions also have to be multi-dimensional, rather than focused around a single variable only. Where no single factor stands out as a necessary or sufficient cause, a broader approach is called for.

The graphic below is discussing Alzheimer’s, but I include it here to illustrate the principle in general.

Taken from ‘The End of Alzheimer’s Programme’ by Dr Dale Bredesen