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Patrick D. McGorry, PhD, FRANZCP; Alison R. Yung, FRANZCP; Lisa J. Phillips, MPsych; Hok Pan Yuen, MSci; Shona Francey, MPsych; Elizabeth M. Cosgrave, MA; Dominic Germano, MPsych(Clinical); Jenny Bravin, MPsych(Neuro); Tony McDonald, MPsych; Alison Blair, MRCPsych; Stephen Adlard, FRANZCP; Henry Jackson, PhD

Arch Gen Psychiatry. 2002;59:921-928.

Background  Most disability produced by psychotic illnesses, especially schizophrenia, develops during the prepsychotic period, creating a case for intervention during this period. However, only recently has it been possible to engage people in treatment during this phase.

Methods  A randomized controlled trial compared 2 interventions in 59 patients at incipient risk of progression to first-episode psychosis. We termed this group ultra-high risk to emphasize the enhanced risk vs conventional genetic high-risk studies. Needs-based intervention was compared with specific preventive intervention comprising low-dose risperidone therapy (mean dosage, 1.3 mg/d) and cognitive behavior therapy. Treatment was provided for 6 months, after which all patients were offered ongoing needs-based intervention. Assessments were performed at baseline, 6 months, and 12 months.

Results  By the end of treatment, 10 of 28 people who received needs-based intervention progressed to first-episode psychosis vs 3 of 31 from the specific preventive intervention group (P = .03). After 6-month follow-up, another 3 people in the specific preventive intervention group became psychotic, and with intention-to-treat analysis, the difference was no longer significant (P = .24). However, for risperidone therapy–adherent patients in the specific preventive intervention group, protection against progression extended for 6 months after cessation of risperidone use.

Conclusions  More specific pharmacotherapy and psychotherapy reduces the risk of early transition to psychosis in young people at ultra-high risk, although their relative contributions could not be determined. This represents at least delay in onset (prevalence reduction), and possibly some reduction in incidence.

From the Early Psychosis Prevention and Intervention Centre (Dr McGorry); Orygen Youth Health (Drs McGorry, Yung, Blair, and Adlard; Mss Phillips, Francey, Cosgrave, and Bravin; and Messrs Germano and McDonald); the Departments of Psychiatry (Dr McGorry, Mss Phillips and Francey, and Mr Yuen) and Psychology (Dr Jackson), University of Melbourne; and PACE Clinic (Drs Yung, Blair, and Adlard; Mss Phillips, Francey, and Bravin; and Mr McDonald), Melbourne, Australia.

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