Risperidone dose and blood level variability: accumulation effects and interindividual and intraindividual variability in the nonresponder patient in the clinical practice setting.

Risperidone blood levels were measured every 2 weeks after initiation of therapy in 24 refractory chronic schizophrenic patients referred to a locked, skilled nursing facility for long-term treatment. Blood levels were assessed on 285 occasions over a 1- to 16-month treatment program. Drug plasma level increases peaked by 2 months for risperidone at 334% and by 6 months for 9-hydroxy-risperidone at 104% over the baseline levels. Total blood levels (risperidone plus 9-hydroxy-risperidone) peaked at 111% increase at 6 months and then declined 8% per month to 12 months, stabilizing at a value 31% higher than the initial value. Significant dose to blood level interindividual variation was noted. Considerable blood level variation was evident in single blood level sample determinations. The results suggest the value of risperidone blood levels, consideration of reduction of initial recommended starting dosages, and a need to optimize risperidone dosage approaches individually to patients.