While antipsychotic treatment is essential for acute and maintenance phases of schizophrenia, antipsychotics can induce various undesirable side effects. Thus, antipsychotic dose and dosing interval should be optimized for each patient. Some of the side effects of antipsychotics, including cognitive impairment, are related to antipsychotic dose. To date, there have been only a few studies examining the effect of atypical antipsychotic dose reduction on clinical outcomes, and there has been no study employing neurocognitive assessments. Based on this background, we conducted a randomized controlled trial and found that atypical antipsychotic reduction significantly improved cognitive function without an increased risk of relapse. In addition, we analyzed the Clinical Antipsychotic Trial of Intervention Effectiveness (CATIE) data, revealing that there were no significant differences in clinical outcomes between once- vs. twice-daily perphenazine dosing regimens; however, the mean dose of perphenazine was significantly lower with once-daily dosing than that with twice-daily dosing. These findings suggest the possibility of effective antipsychotic treatment with lower doses and longer dosing intervals.
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