A Randomized, Double-Blind Study of Paliperidone Extended-Release in Treatment of Acute Schizophrenia in Adolescents

Abstract

Paliperidone extended-release (ER) is approved for treatment of schizophrenia in adults but has not been evaluated in adolescents. In this 6-week, double-blind, parallel-group study, participants (n = 201) aged 12 to 17 years, with a Positive and Negative Syndrome Scale (PANSS) total score of 60 to 120 were randomly allocated (1:1:1:1) to receive either placebo or one of three weight-based, fixed doses of paliperidone ER, once-daily (patients weighing 29 to < 51 kg at baseline: 1.5 mg [Low], 3 mg [Medium], or 6 mg [High]; patients weighing ≥ 51 kg: 1.5 mg [Low], 6 mg [Medium], or 12 mg [High]). The mean (SD) change in PANSS total score from baseline to endpoint (primary efficacy variable) was significant for the paliperidone ER Medium-treatment (-17.3 [14.33]; p < .05; n = 54) but not for Low- (-9.8 [16.31]; n = 48) or High-treatment groups (-13.8 [15.74]; n = 47) versus placebo (-7.9 [20.15]; n = 51). By actual dose, the mean (SD) change in PANSS total score was significant for the 3-, 6-, and 12-mg doses (3 mg: -19.0 [15.45]), 6 mg: -13.8 [14.75], and 12 mg: -16.3 [15.41;] all ps < .05), compared with placebo (-7.9 [20.15]). The total percentages of treatment-emergent adverse events were dose-related for the three weight-based treatment groups. With weight-based treatment, only paliperidone ER Medium-treatment (3-6 mg) resulted in significant improvement in symptoms of schizophrenia in adolescents, as did 3, 6, and 12 mg by actual dose strengths. Weight-based dosing of paliperidone ER in adolescents with schizophrenia does not appear to be necessary. Paliperidone ER (1.5-12 mg, once daily) was tolerable, and no new safety concerns were reported.