Different safety profiles of risperidone and paliperidone extended-release: a double-blind, placebo-controlled trial with healthy volunteers.

OBJECTIVE: The present study investigated subjective experiences related to secondary negative symptoms and cognitive performance in healthy volunteers in response to the repeated administration of paliperidone extended-release (ER) and risperidone in a double-blind, placebo-controlled trial. METHODS: Participants (n = 32) received a fixed dose of one of three study medications for three consecutive days: 6 mg of paliperidone ER, 3 mg of risperidone, or placebo. Subjects were evaluated at baseline and after the first and third administrations of the medications by using the Neuroleptic-Induced Deficit Syndrome Scale and the Scale for the Assessment of Negative Symptoms. Cognitive function was measured at baseline and after the third administration of the medications by using the computerized neuropsychological test. RESULTS: Risperidone was associated with more detrimental subjective experiences compared with paliperidone ER and placebo (p < .05), and these differences persisted after controlling for mental and physical sedation. Analysis of computerized neuropsychological test variables revealed significant differences in the changes in Stroop word-color test results from baseline between the paliperidone ER and risperidone groups (p < .005) and between the placebo and risperidone groups (p < .005). CONCLUSIONS: These results suggest that paliperidone ER may have a better safety profile than risperidone in terms of negative subjective experiences and cognitive function among normal volunteers.