Individualized Risperidone Dosing

To the Editor: The report by Daniel J. Luchins, M.D., and colleagues (1) using computerized pharmacy data provides important confirmation that less rapid titration of risperidone than originally recommended is warranted. The authors also found that patients were more likely to continue taking risperidone if they had a higher maximum dose (5.7 mg/day versus 4.7 mg/day), noting that 5.7 mg/day “is very close to the recommended dose” for this agent. Although the authors do not specifically advocate 5.7 mg/day as the optimum risperidone dose, readers may draw the erroneous conclusion that because patients receiving this dose had higher continuation rates as a group than those taking 4.7 mg/day, the higher dose (5.7 mg/day) is the best risperidone dose for most patients. However, current clinical practice and some recent experimental data argue for highly individualized dosing of risperidone, as well as lower doses (1–5 mg/day) for many patients. Kopala and colleagues (2) found that lower (2–4 mg/day) versus higher (5–8 mg/day) doses of risperidone were associated with superior outcome for all three symptom clusters on the Positive and Negative Syndrome Scale, as well as lower rates of extrapyramidal symptoms. Similarly, Darby and colleagues (3) found risperidone doses ranging from 1 to 6 mg/day useful in their clinical practice (average daily dose in outpatients=3.3 mg) and showed that daily risperidone doses of 4 or 6 mg may produce roughly equivalent blood levels (risperidone plus 9-hydroxyrisperidone) in any two given patients. (These authors also note that the average dose of risperidone in the United States for all patients is 4.7 mg/day, although this does not establish an optimal average daily dose.) For children, adolescents, and elderly patients, Ayd (4) recommends not only a very gradual titration schedule but a ceiling dose of 4 mg/day for several weeks before a higher dose is prescribed. Opler (5) advocates an individualized approach to risperidone dosing, with some patients doing well on doses as low as 1 mg/day and others requiring 16 mg/day or more. My own experience confirms the need for slow titration, highly individualized (often low) doses, and in some cases, the use of plasma levels as a guide to treatment.