Full speed ahead on indicated prevention of psychosis

Fusar‐Poli and eminent colleagues ¹ con­clude their encyclopedic review of prevention in psychiatry by calling for governments to tackle inequalities in young ­people's men­tal health and to invest in improving its so­cial determinants: education, employment, social care, housing, criminal justice, poverty alleviation, social security/welfare benefits, community development, and immigration. We stand firmly with Fusar‐Poli et al on this position and would add social justice and public safety to the list. Academics as individuals and their institutions and professional organizations should assist governments to pursue youth mental health as a top priority.

We further commend Fusar‐Poli et al for their scholarly review of prevention concepts and in particular their noting that both the public health framework and the World Health Organization framework provide the possibility that some disorders carry risk for other disorders and that conceptual boundaries between preventive and treatment interventions can be porous. We often hear in academic discussions that an intervention must be either preventive or a treatment and that an entity must be defined and named either by risk or by severity, as in clinical high risk (CHR) ² vs. attenuated psychosis, or prodromal Alzheimer's disease vs. mild cognitive impairment. Our view has long been that the same intervention can provide both treatment and prevention, and that CHR is both a disorder and an indicator of risk for future more severe disorders. In this context, the term “risk syndrome” ³ may be preferable.

We may part ways, however, with Fusar‐Poli and colleagues on the relative roles of universal and indicated prevention. Notwithstanding the promise of interventions such as phosphatidylcholine and folic acid tested against surrogate biomarkers, the authors' extensive review sadly identifies few if any universal or selective interventions that meet effectiveness, cost‐effectiveness, and implementation standards for reducing the incidence of any mental disorder. The authors' contention that universal public health approaches hold the greatest potential for reducing the risk profile of the whole population does not seem predicated on empirical evidence but rather on theoretical potential.

Along those lines, we take issue with the authors' conceptual Figure 1, partly the basis for their advocacy for universal prevention. This figure shows universal prevention shifting the curve between spectrum of risk and numbers of people to the left, such that there would appear to be no people remaining in the highest risk group who would require indicated prevention. Rather than a shift of a normal curve's x‐intercepts to the left, under a universal approach we would expect to see a skewing of the curve such that the risk x‐intercepts remain fixed, the left side becomes steeper and higher, indicating a larger number of persons at lower risk, and the right side flattens, indicating a smaller but not zero number of persons at higher risk.

In our alternate conceptualization, there would be a continued need for indicated prevention even under conditions of successful universal prevention. This situation appears to be what occurred in the authors' appropriate example of reducing tobacco use in the population, where new incident cases of non‐small cell lung cancer have been reduced by anti‐tobacco measures but have not been eliminated ⁴ .

Fusar‐Poli et al do advocate for combining universal and indicated prevention, and we staunchly support that advocacy. The non‐small cell lung cancer example ⁴ , where mortality has diminished faster than incidence due to the availability of ef­fective new treatments, demonstrates the value at least of tertiary prevention and a potential role for indicated prevention even in the context of effective universal pre­vention.

With regard to the CHR syndrome as a vehicle for indicated prevention of psychosis, one of the recent criticisms of the approach, echoed by Fusar‐Poli et al, derives from the NEMESIS‐2 cohort report that antecedent mood disorders account for more of the incidence of clinical psychosis than do psychotic‐like symptoms ⁵ . We see three important limitations of the NEMESIS‐2 data that have received little attention. First, psychotic‐like experiences gauged through questionnaires or non‐clinical interviews in the general population are not comparable to clinician‐assessed CHR syndromes ⁶ . Second, the time‐points in NEMESIS‐2 were spaced three years apart. Partly‐prospective data show that the average duration of CHR symptoms is two years or less in two‐thirds of patients converting to psychosis ⁷ , suggesting that the development of psychotic‐like symptoms prior to psychosis may have been missed by the NEMESIS‐2 design in as many as half the cases. Third and most crucially, the average age of cohort members at the second time point was 47.7 years, far older than the 12‐to‐early 30s range where CHR has been reported to predict psychosis and where the incidence of psychosis is known to be highest ⁸ . As a consequence of these limitations, in our view the NEMESIS‐2 data are only partially relevant to the value of CHR as a vehicle for indicated prevention.

With regard to evidence for the success of preventive interventions for CHR, Fusar‐Poli et al rightly point out that meta‐analytic evidence so far is contradictory and that clinical trials featuring conversion to psychosis as their primary outcome require very large sample sizes. We do, however, see hope on the horizon. This past fall the US National Institute of Mental Health and the Foundation for the National Institutes of Health announced the Accelerated Medicines Partnership in Schizophrenia (AMP SCZ), a collaborative effort to advance early intervention for CHR individuals ⁹ . This initiative seeks to identify parameters for future clinical trials on alternate outcomes of CHR such as social functioning or attenuated positive symptoms. These alternate endpoints can also potentially serve as surrogate outcomes for reducing the incidence of psychopathology, which can then be investigated directly after entry of the new treatments into clinical practice through epidemiologic methods.

In conclusion, our view is not only that a combined universal and indicated approach is likely to be the best way to prevent psychosis in the future, but also that the CHR syndrome for psychosis continues to provide the most promising option for the indicated prevention component. We acknowledge a potential bias, working as we do in the CHR field, but we like to think we chose this field because it offers the best opportunities in psychiatry for improving public health rather than that we believe it offers the best opportunities for public health because we have chosen it.