Preventing the Onset of Psychosis: Not Quite There Yet

Several hundreds of published reports have explored the construct of a clinical high risk (CHR) state for psychosis, with 11 randomized control trials testing the efficacy of psychological, pharmacologic, nutritional, and multicomponent psychosocial interventions for preventing psychosis onset. Meta-analyses of these randomized controlled trials (RCTs)1,2 suggest that preventive interventions exert a positive, if moderate, impact on transition to psychosis over 12 months (~50% risk reduction among at-risk individuals). Promising results have been reported for cognitive-behavioral therapy, alone or in combination with family therapy, and omega-3 fatty acids. Available data do not support antipsychotic medications as a first-line treatment for CHR patients.1,3 The Early Detection and Intervention for the Prevention of Psychosis Program (EDIPPP) study was developed “to demonstrate that by intervening early with young people who show signs of a potential psychosis, the development of frank psychosis and functional impairment could be delayed or prevented.”4 A multicomponent intervention package, including case management, supportive counseling, multifamily group therapy, supported education and employment, and antipsychotic medication, was offered for 2 years to individuals who met criteria for CHR or early first episode psychosis (EFEP). In contrast to other CHR prevention trials, clinical effectiveness in EDIPPP was evaluated with a quasi-experimental design that compared outcomes for CHR/EFEP patients to youth at clinical low risk (CLR) for developing psychosis. Only CHR and EFEP patients received the EDIPPP intervention; CLR participants were monitored monthly, but were not offered treatment. Results suggest that active treatment may have helped those at CHR but, due to design limitations, EDIPPP findings cannot be considered conclusive. Within-group change scores suggest that CHR and EFEP patients improved over time on measures of symptoms and global functioning. Without a control group, however, one cannot determine how much of the clinical improvement observed for CHR was associated with the active intervention. Likewise, it is impossible to state whether psychotic events were truly averted among treated CHR participants as the design lacked a matched comparison group. Contrary to the authors’ assertions,5 general application of the EDIPPP model for all individuals with early symptoms may be premature. Given that the EDIPPP model involves administration of antipsychotic medications to youth who may never develop frank psychosis, further controlled trials are needed before the model is widely adopted. Data from other randomized control trials suggest that cognitive therapy is a sensible first-line intervention for those at high risk but not yet psychotic.1,2 Additional RCTs are necessary to expand knowledge regarding effective interventions during the CHR period and to build an evidence base to support high-quality community care. Clinical staging or stepped care models have been suggested as a framework for future effectiveness studies.6 In 2013, the National Institute of Mental Health announced a multiyear initiative to support randomized trials to inform a step-wise approach to CHR care (http://grants.nih.gov/grants/guide/rfa-files/RFA-MH-14-211.html). We expect this research to generate effective first-line and secondary interventions for individuals who meet CHR criteria, and to provide valuable information concerning risk mechanisms, targeted interventions, and strategies for adjusting treatment over time. Vulnerable youth, their families, and clinicians deserve our best efforts to develop empirically validated, scalable interventions that forestall psychosis onset and foster functional recovery among those at greatest risk.