1. when n=many

Posted on Tuesday 23 August 2011

In the case mentioned in the last few posts, our discussions of her earlier life suggested to me that the process that later became manifest Schizophrenia had always been present. But had we seen her as a child, we wouldn’t have thought that. She didn’t even really fit the schizoid personality type described by Eugen Bleuler. And when her identity confusion began to show in college, her family worried, but had no inkling of what the future held – nor did the psychiatrists who saw her when she returned to Atlanta and was working at the Bank. It was only after she contemplated suicide and moved back home that the magnitude of her illness became apparent. And even then, the possibility of incipient Schizophrenia was only that – a possibility.

In diseases with a chronic, deteriorating course, treatment strategies often involve Preventive Medicine – aiming to intervene before the disease has begun to take it’s toll. Classically, the Medical Model of Disease addresses the diagnosis and treatment of existing disease. The Preventive Medicine Model refines that traditional approach.


Level Definition

Primary prevention Primary prevention strategies intend to avoid the development of disease. Most population-based health promotion activities are primary preventive measures.
Secondary prevention Secondary prevention strategies attempt to diagnose and treat an existing disease in its early stages before it results in significant morbidity.
Tertiary prevention These treatments aim to reduce the negative impact of established disease by restoring function and reducing disease-related complications.
Quaternary prevention This term describes the set of health activities that mitigate or avoid the consequences of unnecessary or excessive interventions in the health system.

So Primary Prevention is aimed at preventing disease ever occurring in the first place. Immunizing children for infectious diseases is a well known and powerful example. Vaccinations for smallpox or polio have essentially eliminated these formerly widespread virulent diseases. Secondary Prevention is more widely known as ‘early detection.’ Well known examples are PAP Smears, Mammograms, or Colonoscopies – procedures designed to detect diseases at the earliest possible moment before they can do their damage. Tertiary Prevention is traditional medicine, treating an existing disease to prevent further damage or deterioration. Quartenary Prevention is the effort to minimize the negative impact of medical interventions – avoiding unnecessary surgery or preventing over-medication in psychiatric conditions. In psychiatry, Preventive Medicine was the rallying cry of the Community Mental Health Movement in the 1960s.

In this era of gloom about the downside of antipsychotic medications – both first and second generation drugs – it’s easy to forget the historical fate of patients with Schizophrenic Illnesses. In earlier times they were killed as witches, shunned by society, or confined to institutions where many suffered the deteriorating fate described by Kraepelin. Before neuroleptics, the treatments were ominous in themselves: lifelong institutionalization, electro-convulsive therapy, insulin coma therapy, psychosurgery. The doctors who attended the patients were called "alienists" – highlighting the prevailing view of the afflicted. So the introduction of medication that attenuated psychosis was hailed as a near "miracle," and it still looks that way sometimes. I still recall the day the patient I described earlier first appeared in my waiting room psychotic. She moved rapidly from laughter to terror, agitation to absolutely frozen, and the things she said were unintelligible. The sister who brought her was clearly terrified, almost as agitated as the patient. When I said, "Let’s walk across the street to the hospital," the patient followed as if given a military command. And while they were doing the intake on the ward, I had another patient – her sister who was visibly shaken by finding her sister in such a state. Not many days later, when the patient was no longer actively psychotic, I happened to show up on the ward when her sister was visiting. She used the word "miracle" herself describing the change.

But even in those salad days when the antipsychotics first appeared, it was obvious that the drugs were no cure. They are most effective in acute illness, their effectiveness waning depending on the type and chronicity of the illness.  Around the same time, there was a lot of excitement about the success of early intervention strategies with combat neuroses in World War II. So Preventive Medicine came to mental health as the Community Mental Health Movement, the with government financed public mental health clinics all over the country. There were three goals: to provide ongoing services for the patients leaving the hospitals, to treat people in the community to prevent "institutionalization," and to make mental health treatment readily available in a variety of mental illnesses to "catch it early" and treat it vigorously. Hospitals were for acute treatment short term and stabilization. It was a bold program – expensive, but not so expensive as the cost of maintaining the huge state mental hospitals of the era. And like all new paradigms, it began with an almost evangelical fervor, and then fell into decline when its limitations became apparent and the enthusiasm for paying for it dampened.

Whatever the overall fate of the Community Mental Health Movement, the consensus remains that for Schizophrenia, early detection and vigorous treatment of the first episode is the gold standard. One of the leaders in designing and implementing early intervention  programs is Dr. Patrick McGorry in Australia:

Early intervention in psychotic disorders:
detection and treatment of the first episode and the critical early stages

by Patrick D McGorry, Eóin Killackey and Alison R Yung
Medical Journal of Australia 2007 187: S8–S10.

• The two main goals of early intervention in psychotic disorders are to reduce the period of time between the onset of psychosis and the commencement of effective treatment, and to provide consistent and comprehensive care during the critical early years of illness.
• Effective care during the critical early years involves proactive engagement and initiation of drug and psychosocial treatments, aiming for maximal symptomatic and functional recovery and the prevention of relapse.
• Over the past 15 years, an increasing number of specialised or streamed treatment delivery systems for early psychosis have been established around the world. There is now evidence that these services can reduce the duration of untreated psychosis and produce better symptomatic and functional recovery. In addition, they are more cost-effective than standard models of mental health care for these patients.
• Fully fledged, specialised early intervention services should be established, with full integration with local communities, as well as enhanced primary care systems focused on young people.
Dr. McGorry and his colleagues also focused their attention on the prodromal syndrome, hoping to move prevention back a notch:
PACE: a specialised service for young people at risk of psychotic disorders
by Alison R Yung, Patrick D McGorry, Shona M Francey, Barnaby Nelson, Kathryn Baker, Lisa J Phillips, Gregor Berger and G Paul Amminger
Medical Journal of Australia 2007 187: S43-S46.

• Intervention in the prodromal phase of schizophrenia and related psychotic disorders may prevent or delay the onset of these disorders, or reduce the severity of the psychosis.
• Identifying the schizophrenia prodrome is difficult, however, because of its non-specific symptoms and the wide symptom variability between individuals
• Over the past 15 years, we have investigated the schizophrenia prodrome and developed criteria for detecting people suspected of experiencing a prodromal phase [ie, they are thought to be at imminent risk of onset of a psychotic disorder]. About 35% of those meeting our criteria have developed a psychotic disorder within 12 months.
• We have established a clinical service, the PACE [Personal Assessment and Crisis Evaluation] Clinic, for people with suspected incipient psychosis, and trialled interventions aimed at preventing or delaying the onset of psychotic disorders.
• Our results and studies in other countries seem to indicate that psychological and psychosocial interventions, either alone or in combination with pharmacotherapy, may be effective in at least delaying, if not preventing, the onset of a psychotic disorder.
I picked this latter article for the description of the downside of intervening prior to the onset of overt psychosis and how they defined the prodromal syndrome:
Disadvantages of prodromal intervention
One of the main problems with attempting prodromal intervention is the possibility of “false positives”; that is, people who are identified as being possibly prodromal [at risk of developing a psychotic disorder in the near future], but who do not go on to develop the disorder. Those who are in fact not at risk of developing a psychotic disorder [the “true false positives”] may be harmed by being labelled “prodromal” or at “high risk of psychosis” and may receive treatment unnecessarily. Individuals who would have developed a psychotic disorder, but some alteration in their circumstances [eg, stress reduction or cessation of illicit drug use] prevented this from occurring have been termed “false false-positives”. Clearly, it is impossible to distinguish between these two groups phenotypically at either baseline or follow-up.

The non-specific nature of the most common prodromal features adds to the likelihood of detecting false positives. Indeed, the term “prodrome” should only be used once the full-blown syndrome has developed. Prior to diagnosis with a psychotic disorder, the prodrome should be thought of as a risk factor for psychosis, not as a disease entity [ie, the presence of the syndrome implies that the affected person is at that time more likely to develop psychosis in the near future than someone without the syndrome]. However, if the symptoms resolve, then this degree of increased risk may remit as well. In an attempt to deal with these issues, we have coined a new term — the “ultra high risk” [UHR state. We have developed UHR criteria that attempt to identify individuals with a strong likelihood of developing a psychotic disorder in the near future [eg, within 12 months].

Identification of the ultra high risk population
Due to the non-specific nature of prodromal symptoms, there are problems using these features alone to identify people thought to be at imminent risk of onset of psychotic disorder. Even psychotic-like experiences [attenuated or subthreshold psychotic symptoms] have been found to occur commonly in the general population, especially among adolescents and young adults. Using symptoms alone would result in a high false-positive rate. Thus, some added criteria were needed to focus on those most likely to be in the prodromal phase of a psychotic disorder. We added the risk factor of age, as the age of highest incidence of psychotic disorder is adolescence and young adulthood. Clinical need for care was another factor. Thus, the young person must be seeking help, or be identified by someone, such as a parent or teacher, as needing help. This requirement reduces the chance that a well person who happens to have psychotic-like experiences, but who is otherwise functioning adequately and is not distressed, will be unnecessarily treated for imminent psychosis.

We hypothesised that individuals with these multiple risk factors for psychosis would have a high likelihood of developing a psychotic disorder within a short time period. To test this theory, specific operationalised UHR criteria were developed to identify a young person at risk for psychotic disorder. The UHR criteria require that a person is aged between 14 and 25 years, is referred for health care to a psychiatric service, and meets the criteria for one or more of the following groups:

    • Attenuated psychotic symptoms group: patients have experienced subthreshold, attenuated positive psychotic symptoms during the past year;
    • Brief limited intermittent psychotic symptoms group: patients have experienced episodes of frank psychotic symptoms that have not lasted longer than a week and have spontaneously abated; or
    • Trait and state risk factor group: patients have schizotypal personality disorder or have a first-degree relative with a psychotic disorder and have experienced a significant decrease in functioning during the previous year.
These criteria are described in more detail elsewhere. To further reduce the risk that well functioning individuals will be identified, since 2006 we have also required that all patients show a significant deterioration in social or occupational functioning.

Validation of the UHR criteria
To test our model, we established a specialised service for the UHR group — the PACE [Personal Assessment and Crisis Evaluation] Clinic — in Melbourne in 1994. This service was the first clinical and research clinic in the world for individuals considered to have incipient psychosis.

Using the UHR criteria, we found a rate of transition to psychosis within 12 months of about 35%, a rate several thousand-fold greater than the expected incidence rate for first-episode psychosis in the general population. This occurred despite the provision of case management and antidepressant medication if required. The primary diagnostic outcome of the group who developed psychosis was schizophrenia [65%]. The UHR criteria used in PACE have been adopted by a number of other centres around the world.

Dr. McGorry and his group have successful early intervention programs in place. They’ve worked at defining the prodromal syndrome. He was chosen as the Australian of the Year in 2010. He convinced the Australian government to fund a $400 M program for a massive preventive intervention program. He’d done his homework. I suppose if you were going to pick someone to do a study on medication intervention in the prodromal syndrome, you couldn’t find a better qualified candidate. But that’s not what the headlines say now. They have the phrase, "The McGorry Contraversy" – coming next…
    August 24, 2011 | 8:55 AM


    “Opponents (of EPPIC)… wonder whether it makes sense to leap fairly blindly to an expensive and unproven national prevention model based only on quite limited outcome findings that are subject to different interpretations and may not generalize at all well to the real world.”

    Indeed. The fate of early mammography and PSA is instructive.

    “What concrete safeguards will Dr McGorry build into the day to day clinical practice and quality control of the EPPIC program to prevent the overdiagnosis of “prepsychosis” and of schizophrenia and the overuse of antipsychotic medicine?”

    Great question. What’s the over-under that the answer to this question is “probably no safeguards at all”?

    August 24, 2011 | 9:35 AM

    This series strikes me as the “gold standard” for presenting CME (grin). As more clinicians find your blog, they will be treated to your wonderful teaching style! Thanks so much for presenting this.

    A couple of questions come to mind re: levels of prevention and concomitant treatment approaches. Why aren’t therapeutic diets used when prodromal symptoms are first identified? I’m thinking more specifically of elimination diets such as gluten free, no added sugar, no processed foods. There is, albeit limited and older, evidence to support the use of ketosis in treating positive symptoms.

    I think I’d be looking at interventions that allow for some control of confounders, give the patient some concrete things to do in terms of life regulation (sleep/rest hygiene, diet, activity, use of natural daylight/ circadian rhythm regulation, etc) and see if there is a response in either direction in terms of symptoms and quality of life.

    (I’m not sure that I agree with your implied premise that patients are no longer shunned. The NIMBY for housing, the acceptance of people existing on the streets and in shelters, the low rates of employment, etc. point otherwise.)

    August 24, 2011 | 4:17 PM

    “I think I’d be looking at interventions that allow for some control of confounders, give the patient some concrete things to do in terms of life regulation (sleep/rest hygiene, diet, activity, use of natural daylight/ circadian rhythm regulation, etc) and see if there is a response in either direction in terms of symptoms and quality of life.”

    I 2nd that.

    August 25, 2011 | 11:26 AM

    “What’s the over-under that the answer to this question is “probably no safeguards at all”?” ~3 to 1

Sorry, the comment form is closed at this time.