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 onlyWhere 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

Adjunctive or supplementary interventions

Having some wariness of drug interventions needn’t entail that we dismiss out of hand any role for ‘therapeutic molecules’. Trials are looking at the role adjunctive treatments can play. Among them CannabidiolOmega-3 oils and N-acetyl-cysteine (NAC). The latter appears to be a safe intervention that can regulate glutamertergic signalling — which neuroscientists identify as one mechanism potentially leading to psychosis.

Although such ‘supplementary’ treatments are generally assumed to be of marginal benefit, their risk profile is accepted as low. And I think it is fair to surmise that the benefits of such interventions may be masked in trials where patients are maintained on higher doses of one or more psychiatric drug.

Combining such adjunctive treatments may add up, synergistically, to more significant benefits and for symptomology more broadly, including the ‘negative’ and cognitive symptoms that ‘antipsychotics’ don’t help.

Ameliorating factors like oxidative stress, neuro-inflammation and mitochondrial dysfunction with such interventions may have ‘neuroprotective’ effects, as well more general health benefits. This could contribute to better levels of ‘functioning’ and sense of well-being. Interventions like these can be made safely and at relatively low cost. So what is there to lose?

At the end of Part one, I noted that neuroleptics cause cerebral atrophy. This is a rather grim fact. But the brain is a remarkable thing, and there is not a simple relation between the function of the mind and the matter of the brain. Neuroplasticity and neurogenesis are scientifically established phenomena.

Suitable exercise, mental stimulation and appropriate nutrition can be conducive factors allowing for recovery of healthy brain function. Awareness of this potential should, at least, have a role to play in guiding how services approach ‘sustaining remission’, and the advice they offer.

To take just one example that might warrant further research, there is some indication Lion’s Mane mushroom used as a supplement may aid recovery from nerve damage. “Pre-clinical testing found the lion’s mane mushroom had a significant impact on the growth of brain cells and improving memory”. Shouldn’t psychiatric researchers be interested in knowing more about the potential of such ‘nutraceuticals’?

Why is there such resistance to alternative approaches?

Research programmes tend to be based around identifying single causes and proposing mono-variable interventions. Consequently, approaches that don’t easily fit into this research model – focused around RCTs – will likely not be given fair consideration.

For instance, the Bredesen Protocol, thought to be a quite promising approach to Alzheimer’s disease, has been discounted because it isn’t “targeting a common underlying neuropathological process of Alzheimer’s disease”. But the point is, that the existence of such a ‘common underlying process’ cannot simply be taken for granted.

A focus on identifying single factors may well be reasonable scientific practice in many fields. But it may belie the nature of living, adapting, neuroplastic, incredibly complex and sensitive human brain and nervous system.

Moreover, the funding model for healthcare research, in general, seems geared towards developing patentable and marketable products. An imperative that prejudices those whom have the final say, about what proposed solutions should look like. This then blinkers society at large against potentially helpful interventions that don’t fit the established pattern and its assumptions.

In summary

Until such time as there is a comprehensive understanding of causality in the brain and nervous system, with low-risk drug treatments truly proven as safe and effective; mental health services should prioritise harm reduction. Here are some suggestions, perhaps readers can add to them:

  • Allow time for ‘help seeking’ individuals to get support and respite in less jarring settings. Taking a ‘watch and wait’ approach before resorting to the use of neuroleptics.
  • The provision of psychosocial support and resources to enable patients to come to terms with altered experiences, should be given equal weight with drug based management of symptoms.
  • Any ‘critical period’ of neural plasticity in the typical age group for onset of FEP should caution against immediate intervention with psychotropic drugs — against the current presumption in favour of use at the earliest. Perhaps there may be some limited role for sedatives in the more acute stages of a crisis.
  • The prescription of SSRIs (and also SNRIs) to those with milder mental health problems should be avoided. They’ve been shown to increase the likelihood of patients developing more intractable issues. Greater education on the drug interactions and risks of pharmaceutical psychotropics, for both prescribers and patients, is required.
  • Reducing the toll of neuroleptics and other drugs on those who already have treatment histories should be a greater priority than present. Moncrieff et al have proposed that there is a need for specialist ‘deprescribing services’. So that the risks of clinically mismanaged drug discontinuation — currently commonplace through lack of awareness — can be properly addressed. Alternatively, ensuring there are staff members on teams that have this training and understanding — in order to support those stable in remission to reduce step-by-step according to hyperbolic tapers, and as their personal circumstances allow. Enabling ‘managed reduction’ should reduce the temptation for service users to discontinue covertly.
  • An understanding of ‘dopaminergic supersensitivity’ and ‘rebound’ effects from drug withdrawal must also inform both the design and evaluation of trials of ‘antipsychotics’.
  • Research should focus not only on mono-variable interventions, but allow for a broader range of complimentary measures. Accordingly, there may be a need for research to incorporate ‘observational’ and other methods of evaluation, rather than relying solely on RCTs.
  • Services should encourage and support patients to take up regular exercise, and also to eat healthily; providing advice on suitable nutrition for maintaining recovery.

Pragmatically, we should be exploring a raft of safe interventions, understanding that any susceptibility to psychosis isn’t separable from a person’s general health and well-being. By covering more bases (at least the easier ones to cover), finding and sustaining incremental gains, we may enable ‘recovery’ in a fuller sense of the word.


*Pimaversin’s mechanism of action is said to be unestablished, but thought to be due to antagonist effects on serotonin receptors. If a drug that dampens serotonin receptors is considered to have an antipsychotic effect, this would underscore the risk of SSRIs triggering psychosis and mania. SSRIs heighten serotonergic signalling.

** Due to the heavy side effect profile of ‘antipsychotics’, it is very likely that trial participants taking them will realise they are not in the placebo group. This is likely to produce an expectations effect that would reinforce any subjective perceptions of improvement.If you had rapidly gained weight after starting the pills, it would be natural to want to believe they were of some benefit to your mental health symptoms, wouldn’t it?Such effects will likely boost the apparent efficacy of the drugs in research trials. In fact, low levels of weight gain amongst trial cohorts can be taken by researchers as indicating poor adherence to a trial’s antipsychotic drug regime.

*** Pilot and feasibility trials assessing the efficacy of psychosocial intervention compared to antipsychotics:Orygen, Melbourne, Australia: Psychosocial intervention with or without Antipsychotic medication for first episode psychosis UK NIHR 2020 feasibility trial: antipsychotic medication versus psychological intervention…adolescents with first episode psychosis Manchester 2018: Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study Although the papers indicate that there may have been some use of medication in the placebo/psychosocial treatment arms, the trials at the very least, show that dosing much lower than standard does not simply translate into a loss of therapeutic effect. Which is, in itself, an important finding encouraging of greater openness towards deprescribing. Especially, when combined with an understanding of the ‘hyperbolic’ relation between dose and D2 receptor occupancy. Mark Horowitz’s work shows that very low doses can be efficacious.

**** An evaluation of projects run on the Soteria model noted the “importance of a consistent, emotionally relaxing therapeutic environment.” Mainline acute wards can sometimes be a long way from providing that. The prevalence of acute patients being transported by police, or subject to restraint and coercion is also clearly far from this ideal.


  1. “The prescription of SSRIs (and also SNRIs) to those with milder mental health problems should be avoided”.

    Yes indeed, and they should only be prescribed with Fair Full and Informed Consent.

    This MUST include prescriber understanding, awareness of, and training in the recognition and management of AKATHISIA; with its associated DISINHIBITION and EMOTIONAL BLUNTING. This is not achieved by increasing the dose or changing the antidepressant.
    Families, partners and loved ones should also be made aware of AKATHISIA and its risk of prescription drug induced suicidality and violence. They should also be aware of the risk of AKATHISIA MISDIAGNOSIS.

    Those who misdiagnose AKATHISIA as “Psychosis” or Serious Mental Illness (SMI) and then ‘Section’, detain, force-drug and subject patients (who have NO SMI) to (televised) trauma, abuse and contempt which is allegedly ‘psychiatric nursing’: – MUST apologise for the GRIEVOUS PHYSICAL, PSYCHOLOGICAL, EMOTIONAL, SOCIAL and ECONOMIC iatrogenic HARM caused to people who were completely healthy and normal prior to predictable ADRs. (It is recognised that many other classes of prescription drugs can cause akathisia and/or induce reactions/toxicities that may appear to be due to mental illness).

    Post SSRI SEXUAL DYSFUNCTION should be recognised, accepted, and above all: – avoided by prescriber awareness that these drugs have been used in ‘Voluntary chemical castration of convicted sex offenders’.

    Too many lives lost, futures destroyed, families destroyed and unjustified deprivation of liberty for the current ignorance of and/or denial of these ADRs to continue without financial redress; where there has not been the opportunity to refuse these (and other psychotropic drugs) via valid, informed consent.

    How many of those politically vilified for not being in employment are unable to work due to multiple psychotropic drug injuries? Iatrogenic unemployment?

    If we are to save the NHS, we have to face recognising its greatest failures.

    Failure to recognise the above has continued for over 30 years.