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Objective: Interest in the “at-risk mental state” (ARMS) for psychosis has increased because early intervention is expected to delay or prevent the onset of schizophrenia. However, the optimum intervention strategy remains controversial, especially with regard to antipsychotics. Although administration of antipsychotic medications is often associated with adverse effects and raises ethical considerations, recent studies have shown that some novel antipsychotics are safer and more tolerable for young people than conventional antipsychotics. We investigated whether administration of perospirone, a combined serotonin (5-HT)/dopamine antagonist and 5-HT1A receptor agonist, could alleviate prodromal symptoms and be well tolerated by clinical high risk patients. Methods: The participants were outpatients seeking help. The Structured Interview for Prodromal Symptoms was performed in patients identified as being at clinical high risk. The Scale of Prodromal Symptoms (SOPS) was also completed and changes of subjective experience were assessed with the Subjective Well-being under Neuroleptics, short version. The incidence of akathisia was recorded by using the Barnse Akathisia Scale (BAS). Subjects were monitored for 26 weeks after starting medication. Results: SOPS scores improved significantly after 26 weeks of perospirone therapy, while BAS scores did not show deterioration. No serious adverse events occurred during the study. Conclusion: This trial suggests that perospirone therapy provides a clinical benefit for clinical high risk subjects without causing serious adverse events. Although further placebo-controlled studies are needed for confirmation, perospirone might be one of optimum treatments for individuals at imminent risk of psychosis.

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