Optimal Dosing and Long-Term Effects of Risperidone

The establishment of appropriate dose ranges and dose-up strategies for antipsychotic drugs has important ramifications for both short-term treatment and long-term therapeutic outcomes. The drug dosages utilized during controlled clinical trials are not always optimal for patients encountered in day-to-day practice. The original trials of risperidone, a novel antipsychotic drug, suggested that an initial target dose of 6 mg/day to be attained after a dose-up schedule of 1 week was appropriate, but most of the patients included in these trials were chronically impaired, hospitalized and often partly drug resistant. Relevant data relating to the dosage and dose-up schedule of risperidone has been garnered through numerous clinical studies, such as multicenter studies, naturalistic studies and phase 4 trials. These studies reported that the currently recommended target dose for risperidone treatment is 4-5 mg/day with less-rapid titration than that indicated in the original trials, which is lower than previously recommended. Moreover, a lower dose than this and slower titration may be appropriate for elderly patients and first-episode patients. Longterm clinical studies of antipsychotics provide information about their delayed efficacy or late-onset adverse events, such as tardive dyskinesia, functional recovery, relapse or about recurrence rates and maintenance treatment. The number of well designed long-term studies is limited, because of practical reasons as well as some methodological issues. In this review, the authors summarized original research papers on the initial dosing strategies and long-term treatment outcomes of risperidone, while discussing the methodological considerations.