Treatment models and designs for intervention research during the psychotic prodrome

Recently, interventions for the psychotic prodrome have gained considerable interest. The goal of early interventions for prepsychotic, but symptomatic, individuals is to reduce disability and impairment by ameliorating subpsychotic symptoms and, potentially, preventing the progression into a full-blown psychotic disorder. However, several central questions regarding early interventions for the psychotic prodrome require clarification: Is it possible to prevent or to delay the onset of a psychotic disorder by intervening in the prodromal state? Is it possible to alter the natural course of the illness; i.e., to reduce subsequent symptom severity, relapse rates, treatment refractoriness, and/or functional disability, by treating subsyndromal symptoms? What is the relationship between treatment response of prodromal symptoms or specific symptom clusters and the prevention of disease progression or improvement of functional outcome? In the context of these questions, different treatment models and trial designs are presented, focusing on patient selection, target symptoms, interventions, control conditions, outcome measures, trial duration, and exit strategies, as well as statistical and ethical considerations. Finally, the methodology of completed and ongoing intervention trials in putative prodromal populations is discussed.