Right of Reply – Patrick McGorry on Early Intervention for Psychosis

In the interests of balance I have posted below a blog prepared by Professor Patrick McGorry.

Professor McGorry prepared his blog entry in response to criticism by me (Australian of the Year Patrick McGorry’s call for early intervention to prevent Psychosis: A Stitch in Time or a Step too Far?) and others of his past advocacy of antipsychotics as a measure to prevent psychosis and his support for the inclusion of a Psychosis Risk Syndrome in the next edition of the handbook of psychiatry, DSMV.

Following Professor McGorry’s blog is my response which details his past advocacy of the pre-psychosis use of antipsychotics, welcomes his recent change of heart but challenges him to join with his long term research partner, Dr Alison Yung, and oppose the inclusion of a Psychosis Risk Disorder in DSMV.

Responding at the earliest opportunity to emerging mental illnesses – by Patrick McGorry

6 December 2010 – 11:01am copied with permission from http://www.patmcgorry.com.au/blog/pmcgorry/responding-earliest-opportunity-emerging-mental-illnesses

One of the most important areas in mental health research is exploring how to delay or prevent the onset of severe mental illnesses such as psychotic illness, especially schizophrenia.   Twenty years ago this possibility was out of reach.  Now thanks to Australian-led research it is much closer.  Yet despite the great potential for this emerging field to avert distress, disability and death, it remains poorly understood within the community and recent progress is often actively misrepresented in the media and public discourse.  Such confusion and misrepresentation creates unnecessary public anxiety and risks weakening the imperative to provide safe forms of early intervention for those most in need.  I am writing this piece with the goal of clarifying the issues, the latest evidence and my own views which derive directly from the scientific evidence base and twenty years of clinical experience in this field.

Summary of key points

• Mental ill-health and a need for support, assessment and care, precedes the onset of psychotic symptoms in most people who develop a psychotic illness, especially schizophrenia.
• It is now possible to recognize in advance a set of symptoms which indicate a much greater risk for developing clearcut and severe psychotic illness.
• This enables safer and potentially more effective treatments to be offered prior to the onset of psychosis which aim to firstly respond to the immediate problems, symptoms and functional disability that has already manifested, and to secondly try to reduce the risk of progression to more severe forms of ill-health, particularly but not exclusively psychotic disorder.
• The support and interventions should be offered in a stepwise way, starting with personal support and information, supportive case management and problem-solving, moving onto trials of CBT and omega 3 fatty acids, all of which have a good risk benefit ratio.  Anti-depressants may also be considered if depression is severe and has not responded to CBT.
• Antipsychotic medications should not be considered unless there is a clearcut and sustained progression to frank psychotic disorder meeting full DSM 4 criteria.
• The only exception to the previous statement is where there has been a definite failure to respond to the first and second line interventions described above AND there is worsening and continuing disability, or significant risk of self-harm, suicide or harm to others arising directly from the mental disorder itself and its symptoms. In this situation, a trial of low dose antipsychotic medication for 6 weeks in the first instance may be appropriate, with careful monitoring for adverse events.
• All such care must be offered in stigma-free environments such as primary care or youth mental health settings and not in services designed for the care of the seriously mentally ill.
• Further research is required to define a clearer evidence base to guide stepwise decision making in the treatment of the pre-psychotic stage of early psychosis.

Psychosis can be devastating for individuals, their families and weakens our society.  Emerging in young people on the threshold of productive life, it poses a huge threat to health, career, personal fulfillment and even survival.   As a matter of equity, people who are experiencing psychosis or have a high risk of doing so should enjoy the same access to stigma-free quality care in a timely fashion just as is routinely the case with physical illnesses of comparable severity.

 Just as with heart disease and cancer, every reasonable effort should be made to avert as much distress, discomfort and long term collateral damage from psychosis as is possible. What that means in practice is identifying the earliest opportunities for detection and intervention and the safest and most effective means of preventing and treating emerging psychosis.  Our goal is to modify the impact and course of the illness, that is to preempt the disabling aspects.  Cure probably remains out of reach for most at this stage but substantially better recovery and long periods of freedom from illness are definitely attainable for the majority of people with psychosis.

 Psychosis tends to first emerge in adolescence or early adulthood. Over the last twenty years, it has been demonstrated that early detection, optimum treatment and support for recovery produce much better short and longer term outcomes for young people experiencing their first episode of psychosis.  This evidence also shows that these better outcomes are achieved with lower costs so that precious resources are freed up and can be used to strengthen and expand mental health and social services for other groups of people including those with persistent illness, children and the elderly.

Early detection and specialized care of young people with first episode psychosis and subsequently was initially the main international focus. Yet we have known for a long time that psychotic illness usually builds up over a period of time and is preceded by “prodromal” features, which distress, disable and attract concern and even stigma, yet do not yet manifest clearcut psychotic features such as delusions and hallucinations.  This held out the exciting possibility that we might be able to identify people who were “en route” to psychosis and not only provide care for their current problems but also intervene to reduce the risk of progression to more severe and clearcut psychosis.  

This challenge prompted a key breakthrough, developed originally by my colleague Prof Alison Yung and I in 1994, and elaborated since in many other overseas centres, which has enabled us to identify young people with high levels of risk of developing psychosis within the next year or so.  This was the reliable definition of the “Ultra High Risk” mental state which predicted progression to psychosis surprisingly accurately.  Young people in this “Ultra High Risk” group are already experiencing a range of mental health and social problems, are in need of care and actively seeking help.    They can typically be expected to have between a one in five to a one in two chance of progressing to a first episode of psychosis within 12 months (that is between two and four hundred times the rate within the general population).  They also are at risk of other persistent mental disorders in addition to psychosis.  But in addition to the potential risk, which is significant, they are in immediate need for care for distress and impairment that they are already experiencing.   What that care should consist of is being actively studied and clinical guidelines have been carefully developed based on the evidence and experience accumulated to date.

The Ultra High Risk criteria have been further studied internationally and have been proposed as a new category in the next edition of the DSMV manual, the US based system of diagnosis in psychiatry.  This proposal has been controversial, because of fears of extending antipsychotic medication more widely in the population and fears that labeling people as being at risk (even if already experiencing mental ill-health) may be harmful.   Both of these concerns are valid, though both can and have been addressed in our work and systems of care in Melbourne. 

 One obvious benefit of the ability to engage and monitor young people with a high risk of developing such a serious illness is obviously in reducing treatment delays once the threshold to first episode of psychosis has been reached and thereby to facilitate better outcomes. But aiming higher, can being offered access to care as a member of the Ultra High Risk group benefit a young person by prompting care responses that delay or prevent the onset of a first episode of psychosis?

This important question has been a subject that I and other colleagues, notably Alison Yung, have been researching over the last twenty years. As a result of this and other research – a total of 6 clinical trials now, we can now say that with appropriate intervention, it does appear to be possible to delay the onset of a first episode psychosis amongst members of the Ultra High Risk group. This finding, unimaginable twenty years ago, is highly encouraging as it gives grounds for optimism that further research may establish whether it is also possible to prevent the onset of a first episode psychosis within this group.  Several approaches to treatment that have been studied seem to be able to delay the progress to psychosis as well as alleviate the distressing and disabling symptoms that affect people at this stage of illness.

This week at the Seven^th International Early Psychosis Conference in Amsterdam, we launched the most recent version of the Australian Clinical Guidelines for Early Psychosis. These guidelines, which distill the very latest research evidence, specify that recommended interventions for this Ultra High Risk Group are a combination of Omega-3 fatty acids, Cognitive Behavioral Therapy and supportive counseling as well as, in some cases, medication for other diagnosed conditions that may be present (for example depression) as well as psycho-education for family members.

The guidelines explicitly state that anti-psychotic medication should not be considered as a first line treatment option for the Ultra High Risk group. Only in exceptional circumstances, where there is rapid worsening of psychotic symptoms combined with an elevated risk to the young person or others should consideration be given to the use of low dose anti-psychotic atypical medication. Even then, the use of anti-psychotic medication would normally not be justified.  The rationale for this is that safer treatment options should always be offered before those which carry increased adverse effects and risk.  This is a fundamental principle in medical care: “first do no harm”.  Only if the initial safer option fails should progress to the next level occur according to a “staging model” which we have explicitly developed and described in recent publications.  These guidelines restate and reinforce the earlier international guidelines produced by the IEPA in 2005 which my colleagues and wrote in a collaborative fashion with other international experts.   The evidence that has accumulated since that time strengthens the position taken in 2005 – there has been no reversal of that position.

This last point about the use of anti-psychotic medication within this group is very important as the stated position of myself and my colleagues about this issue is occasionally misreported or misrepresented. There is a clear distinction to be made between research trials and clinical guidelines, a distinction which is sometimes not made clear.   Our group in Melbourne has researched a number of potential interventions to reduce symptoms, disability and risk in the Ultra High Risk group,  including befriending, cognitive behaviour therapy, supportive case-management, family support, omega 3 fatty acids, lithium, anitdepressants and  low doses of anti-psychotic medication. All of this research has been approved by an independent ethics committee and all participants have of course provided fully informed consent to be involved.  This results have demonstrated that such not only supportive care, cognitive behaviour therapy and omega 3 fatty acids, but also low dose anti-psychotic medication may be effective in delaying the onset of first episode psychosis.

However, our clinical guidelines do not (and have never done so in the past) recommend the use of anti-psychotic medication as the first line or standard treatment for this Ultra High Risk group.  This is because other, safer interventions are equally effective in delaying the onset of psychosis and, despite the greatly elevated risk, it is equally true that most of the Ultra High Risk group will not experience a first episode of psychosis, so many could be receiving antipsychotic medications unnecessarily.  The key issue is timing and careful consideration of benefits versus risks in consultation with the patient and their family. The most promising initial combination so far is omega 3 fatty acids combined with cognitive-behavioural case-management; safe and effective as first line care.   We therefore believe that further research would be required before it could be known whether and in what circumstances, low dose anti-psychotic medication may have a role later in the sequence of treatment of the ultra high-risk group.  It may be for some patients, in the era of short duration of untreated psychosis, even when they have crossed the threshold to fully-fledged  psychosis, that antipsychotic medications may able to be avoided if expert psychosocial care is available.   This is something we are also researching.  

In summary we are trying to define the sequence of decision points for every patient based the balance between benefit and risk, not only for the present day but also for the future.  And not only for psychotic illness but for several other dimensions of mental ill-health.   This is a mainstream evidence based approach that is fully supported everywhere else in health care.  We need to see it embedded in mental health care too.

Martin Whitely’s response to Patrick McGorry’s Blog

Some welcome news but there is unfinished business- Psychosis Risk Syndrome and the DSMV

I wholeheartedly agree with Professor McGorry’s that the best way to prevent psychosis is ‘appropriate’ early intervention. However, I and other far more qualified critics have passionately disagreed with Professor McGorry’s past advocacy of antipsychotics as an ‘appropriate’ early intervention.

There is reason to be optimistic in the recent blog (copy above) prepared by Professor Patrick McGorry. His statement that ‘Antipsychotic medications should not be considered unless there is a clear-cut and sustained progression to frank psychotic disorder meeting full DSM 4 criteria’ is welcome. It appears to put an end to the debate about whether Professor McGorry currently advocates the use of antipsychotics on the hunch that adolescents will later become psychotic. While it is of some concern that the text immediately following the above statement leaves the door open to ‘off label’ psychosis risk prescribing, Professor McGorry’s is clearly less enthusiastic than he has been for broadening  the use of antipsychotics.^[1]

However, the statement in his blog that ‘our clinical guidelines do not (and have never done so in the past) recommend the use of anti-psychotic medication as the first line or standard treatment for this Ultra High Risk group’ has the potential to mislead. Casual readers may take this to mean that Professor McGorry and his allies have never advocated the use of antipsychotics in order to prevent psychosis.

As stated in my blog a fortnight ago ‘for over a decade Patrick McGorry has experimented with, or advocated, the prescription of antipsychotics to adolescents on the hunch that they may later become psychotic.’ Professor McGorry was the lead author of a 2006 article which as part of a proposed ‘clinical staging framework for psychosis’ identified ‘atypical antipsychotic agents’, as one of the ‘potential interventions’ for individuals who are at ‘ultra high risk (10% to 40%)’ of developing first episode psychosis.^[2] Whilst he has recently adjusted the ‘clinical staging framework’ he was still advocating antipsychotics as a potential pre-psychosis intervention at least as late as October 2007.^[3]

In addition a 2007 British Medical Journal article jointly authored by Dr Alison Yung and Professor McGorry began by quoting 1994 paper by Mrazek and Haggerty extolling the potential of pre-psychosis pharmacological interventions: ‘The best hope now for the prevention of schizophrenia lies with indicated preventive interventions targeted at individuals manifesting precursor signs and symptoms who have not yet met full criteria for diagnosis. The identification of individuals at this early stage, coupled with the introduction of pharmacological and psychosocial interventions, may prevent the development of the full-blown disorder.’

Dr Yung and Professor McGorry’s opening comment followed; ‘Such sentiment underlines the aim of identifying people in the prodromal phase preceding a first psychotic episode.’^[4] Their article went on to outline evidence supporting interventions including antipsychotics ‘to delay or even prevent onset of psychosis.’

Furthermore, in 2008, in the British Medical Journal, in an article titled ‘Is early intervention in the major psychiatric disorders justified? Yes’ Professor McGorry wrote; ‘Early intervention covers both early detection and the phase specific treatment of the earlier stages of illness with psychosocial and drug interventions. It should be as central in psychiatry as it is in cancer, diabetes, and cardiovascular disease….. Several randomised controlled trials have shown that it is possible to delay the onset of fully fledged psychotic illness in young people at very high risk of early transition with either low dose antipsychotic drugs or cognitive behavioural therapy.’ ^[5]

These are just a few of numerous similar statements which comment favourably or suggest the use of antipsychotics as part of the treatment for adolescents considered to be at ‘ultra high risk’ of developing psychosis.  Whether such comments constitute ‘advocacy’ is open to semantic debate however, Professor McGorry certainly favoured this highly controversial use.

Professor McGorry’s argues in his blog ‘that recent progress is often actively misrepresented in the media and public discourse. Such confusion and misrepresentation creates unnecessary public anxiety and risks weakening the imperative to provide safe forms of early intervention for those most in need.’ If there is confusion it is because Professor McGorry has never, even in his blog, unambiguously acknowledged he did favour the use of antipsychotics pre-psychosis and now (recent progress) he does not.

The closest Professor McGorry comes to acknowledging his previous position in his blog is when he states; ‘the use of anti-psychotic medication within this group is very important as the stated position of myself and my colleagues about this issue is occasionally misreported or misrepresented. There is a clear distinction to be made between research trials and clinical guidelines, a distinction which is sometimes not made clear.’

The articles cited above as evidence of Professor McGorry’s past advocacy of antipsychotics were all editorial pieces in which Professor McGorry summarised research and suggested appropriate treatment responses. They may not have been formally endorsed ‘clinical guidelines’ but to use that restricted criteria to imply that he has not previously advocated the use of antipsychotics is spin more suited to politics, the search for power, than science, the search for truth.

Nonetheless, Professor Mcgorry’s change of position is welcomed, however, there are two outstanding issues that require resolution. Specifically the issue of ‘off label’ pre-psychosis prescribing and the inclusion of Psychosis Risk Syndrome or Attenuated Psychosis Syndrome in DSMV. Professor McGorry leaves the door open to ‘off label’ prescribing and persists with his advocacy for the inclusion of a Psychosis Risk Syndrome in the DSMV.

In contrast his long term research partner Dr Alison Yung, presumably because of her long term exposure to the scientific evidence and the related medico-political processes, has changed her position. She is now suspicious enough to ask ‘So why the need for a specific (psychosis) risk syndrome diagnosis? Is the agenda really to use antipsychotics?’^[6]

I share Dr Yung’s suspicion.