Re: Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial
When Professor Morrison and colleagues did the power calculation for their randomised trial they estimated that without active treatment 30% of patients with at risk mental states would go on to develop schizophrenia or a related condition. They based this figure on rates of transition to psychosis in previous experimental and observational investigations. However, half-way through the study the researchers had to amend their primary outcomes to incorporate frequency, severity and distress from symptoms. Only 9% of their control subjects and 7% of those who received cognitive therapy developed a psychotic illness (1).
Early intervention practitioners have been warned about this lowering of the transition rate for more than a decade (2,3). Richard Warner even provided worked examples to illustrate why this would happen in his commentary on a paper by two of the investigators (4). It has occurred because, as we all know, the positive predictive value of a diagnostic test depends on the prevalence of the condition in the population to which it is applied (5). Initial studies were conducted in patients who had been referred by consultant psychiatrists and general practitioners to specialised clinics for a putative schizophrenic prodrome. It turned out that as many as 30%-70% of these patients were, indeed, developing a psychotic illness (6). Clinical and research tools such as the Comprehensive Assessment of At-Risk Mental States predicted with a fair degree of accuracy which patients would become seriously ill. Inspired by this success early intervention for psychosis teams urged general practitioners to lower their referral threshold. They have also encouraged multidisciplinary mental health clinicians, primary care teams, counsellors, ministers, priests, teachers, probation workers, housing officers, and worried families to refer troubled young people directly to their clinics. Not surprisingly, true pre-psychotic states are infrequent amongst these referrals. Hence, assessments of at risk mental states will have a low positive predictive value. The brilliant BMJ paper by Mathers and Hodgkin in 1989 which clearly explains clinical and policy implications of the positive predictive value should be required reading for all early intervention practitioners (5).
Well-meaning claims about the primary prevention of schizophrenia have misled patients, families, journalists and politicians and this has led to a distortion of health care priorities in many countries. However, I have recently gained the impression that the epidemiological and clinical errors that underpin the early intervention for psychosis movement are gradually dawning on its advocates. Perhaps the spectre of “psychosis risk syndrome” or “attenuated psychotic symptoms syndrome” in the next edition of the Diagnostic and Statistical Manual of Mental Disorders has focussed their minds. They are, at last, voicing concerns about the dangers of over-diagnosis and unnecessary treatment with powerful psychological therapies and antipsychotic medicines. Hopefully Morrison and colleagues’ ambitious, important and methodologically admirable study - combined with proper understanding of positive predictive value – will be the start of rational policy making and sensible clinical care for people in the early stages of major mental disorders.
1. Morrison AP, French P, Stewart SLK, Birchwood M, Fowler D, Gumley AI, Jones PB, Bentall RP, Lewis SW, Murray GK, Patterson P, Brunet K, Conroy J, Parker S, Reilly T, Byrne R, Davies LM, Dunn G. Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial. BMJ 2012; 344: e2233 doi: 10.1136/bmj.e2233.
2. Warner R. Limitations of the Bonn Scale for the Assessment of Basic Symptoms as a screening measure. Arch Gen Psychiatry 2002; 59: 470-1.
3. Pelosi AJ, Birchwood M. Is early intervention for psychosis a waste of valuable resources? British Journal of Psychiatry 2003; 182: 196-8.
4. Warner R. Fact versus fantasy: A reply to Bentall & Morrison. Journal of Mental Health 2003; 12: 351-7.
5. Mathers N, Hodgkin P. The Gatekeeper and the Wizard: a fairy tale. BMJ 1989; 298: 172-4.
6. Fusar-Poli P, Bonoldi I, Yung AR, Borgwardt S, Kempton MJ, Valmaggia L, Barale F, Caverzasi , McGuire P. Predicting psychosis. Meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry 2012; 69: 220-9.