Treatment of the schizophrenia prodrome: is it presently ethical?

Although the devastating consequences of schizophrenia have long been known , interest in preventive intervention has only recently emerged. The shift in focus toward early treatment has been encouraged by findings suggesting that the longer psychosis remains untreated, the poorer the prognosis, and by the recent introduction of novel antipsychotic medications with a more b enign side effect profile than conventional neuroleptics. In this paper, we argue that interest in prevention has outpaced the necessary scientific an d ethical underpinnings for clinical trials involving the schizophrenia pro drome. Specifically, we maintain that the prodromal phase of schizophrenia is, at present, essentially a retrospective construct and that, as a result , the defining signs and symptoms currently in use must be validated in nat uralistic, longitudinal studies. In particular, it is essential to establis h solid base rates for schizophrenia in prodromal individuals before early treatment can be effectively evaluated. Additional ethical/scientific issue s discussed include: (1) the need for an exit strategy (i.e. the determinat ion of when to discontinue treatment in an individual who does not develop schizophrenia), (2) the advisability of pharmacological interventions that specifically target neurocognitive deficits, and (3) the possibility that a ntidepressant medications may be as effective or more effective, with fewer side effects, than antipsychotic medication for prodromal individuals. (C) 2001 Elsevier Science B.V. All rights reserved.