Morris B. Goldman, MD Associate Professor of Psychiatry and Behavioral Sciences
Marko Mihailovic, MA, LCPC Clinical Research Manager
Philip G. Janicak, MD Adjunct Professor of Psychiatry and Behavioral Sciences
Northwestern University Chicago, Illinois
Disclosures Dr. Goldman has served as a speaker for PsychU/Otsuka, received research grants from the National Institute of Mental Health, and received income from Sunovion. Mr. Mihailovic reports no financial relationships with any companies whose products are mentioned in this article, or with manufacturers of competing products. Dr. Janicak has served as a consultant to TMS Solutions and Neuronetics and as a speaker for PsychU/Otsuka.
The first generation of RCTs appeared to confirm these results, although sample sizes were small, and most study designs assessed only a single intervention. Initial meta-analyses of these data reported that both CBT and antipsychotics appeared to prevent approximately one-half of individuals from becoming psychotic at 12 months, and more than one-third at 2 to 4 years, compared with treatment as usual.20
While some researchers challenged the validity of these findings,21-23 the results generated tremendous international enthusiasm and calls for widespread implementation.6 The number of early intervention services (EIS) centers increased dramatically worldwide, and in 2014 the National Institute for Health and Care Excellence released standards for interventions to prevent transition to psychosis.24 These included close monitoring, CBT and family interventions, and avoiding antipsychotics when possible.24
Focusing on sensitivity over specificity
The first generation of studies generated by the prevention model relied on outreach programs or referrals, which produced small samples of carefully selected, pre-screened individuals (Figure,Pre-screened) who were then screened again to establish the high-risk sample.25 While approximately 33% of these individuals became psychotic, the screening process required a very efficient means of eliminating those not at high-risk (given the ultimate target population represented only approximately .5% of young people) (Figure). The pre-screening and screening processes in these first-generation studies were labor-intensive but could only identify approximately 5% of those individuals destined to become psychotic over the next 2 or 3 years. Thus, alternative methods to enhance sensitivity were needed to extend programming to the general population.
Second-generation pre-screening(Figure; Step 1). New pre-screening methods were identified that captured more individuals destined to become psychotic. For example, approximately 90% of this population were registered in health care organizations (eg, health maintenance organizations) and received a psychiatric diagnosis in the year prior to the onset of psychosis (true positives).8 These samples, however, contained a much higher percentage of persons not destined to become psychotic, and somehow the issue of specificity (decreasing false positives) was minimized.8,9 For example, pre-screened samples contained 20 to 50 individuals not destined to become psychotic for each one who did.26 Since screening measures could only eliminate approximately 20% of this group (Figure, Step 2, page 25), second-generation transition rates fell from 30% to 40% to 2% to 10%.27,28
Other pre-screening approaches were introduced, but they also focused on capturing more of those destined to become psychotic (sensitivity) than eliminating those who would not (specificity). For instance, Australia opened more than 100 “Headspace” community centers nationwide designed to promote engagement and self-esteem in youth experiencing anxiety; depression; stress; relationship, work, or school problems; or bullying.13 Most services were free and included mental health staff who screened for psychosis and provided a wide range of services in a destigmatized setting. These methods identified at least an additional 5% to 7% of individuals destined to become psychotic, but to our knowledge, no data have been published on whether they helped eliminate those who did not.