Repurposing Medications to Prevent Psychosis in Adolescents with Early Signs of Schizophrenias

Individuals who experience schizophrenias often have premorbid signs as early as childhood. However, they rarely develop pathognomonic psychotic symptoms until adolescence or young adulthood, a period of substantial brain remodeling. Current efforts to reduce risk for psychosis include psychosocial interventions as well as drugs designed to treat existing psychosis in mature individuals. These interventions have shown only modest beneficial effects, on average. This paper reviews evidence suggesting that other existing medications might be more effective in reducing risk of psychosis. Over the last decade, results have accrued on the molecular mechanisms and cellular processes that support healthy adolescent brain remodeling. In addition, studies have identified which of these processes may be inherently abnormal in those at risk for schizophrenias. Some mechanisms have been observed convergently from brain imaging, genomic, and cell culture studies. These mechanisms prominently include abnormal neuronal and glial development and function, compromised synapse remodeling, aberrant energy production, and altered immune functions. A search was performed to identify medications, already in use for other clinical purposes, that are known to target, modulate, and support these mechanisms and processes. Agents with those properties are noted and discussed. These drugs have well known standard doses and effects. They should be considered for trials in adolescents at high risk for psychosis. They might also serve as models for the design of even better-targeted agents to prevent or ameliorate psychosis.