paliperidone-palmitate and Psychomotor-Agitation

To evaluate the efficacy, safety, and tolerability of paliperidone extended release (ER) relative to aripiprazole in adolescent schizophrenia.. In this multicenter, double-blind, phase 3 study (screening [≤3 weeks], with an acute treatment period [8 weeks] and a maintenance period [18 weeks]), adolescents (12-17 years old) with schizophrenia (DSM-IV diagnosis; Positive and Negative Symptom Score [PANSS] total score 60-120) were randomized (1:1) to once-daily paliperidone ER (6 mg per day [days 1-7], flexibly dosed 3, 6, or 9 mg per day from week 2 to end of study [EOS]), or to aripiprazole (2 mg per day [days 1 and 2], 5 mg per day [days 3 and 4], 10 mg per day [days 5-7], flexibly dosed 5, 10, or 15 mg per day [week 2 to EOS]).. Overall, 76% of enrolled patients (174/228) completed the study (paliperidone ER, 75% [85/113]; aripiprazole, 77% [89/115]). There was no significant difference in change in PANSS total scores from baseline to day 56 (primary endpoint) (paliperidone ER versus aripiprazole, -19.3 [13.80] versus -19.8 [14.56], p = .935); responders, 67.9% versus 76.3%, p = .119) and day 182 (-25.6 [16.88] versus -26.8 [18.82], p = .877; responders, 76.8% versus 81.6%, p = .444). All secondary endpoints (maintenance of clinical stability, change in PANSS-negative symptoms, Clinical Global Impression-Severity, and Personal and Social Performance scores) were similar in both treatment groups. The most common (>10% patients) treatment-emergent adverse events for paliperidone ER were akathisia, headache, somnolence, tremor, and weight gain, and for aripiprazole were worsening of schizophrenia and somnolence. Extrapyramidal symptoms including dystonia and hyperkinesia occurred in >2% in paliperidone ER-treated versus aripiprazole-treated patients.. Paliperidone ER did not demonstrate superior efficacy to aripiprazole in treating adolescent schizophrenia. Both drugs showed clinically meaningful improvements in symptom and functional measurements and were generally tolerable. Clinical Trial Registration Information-An Efficacy and Safety Study of Extended-Release (ER) Paliperidone in Adolescent Participants With Schizophrenia; http://clinicaltrials.gov; NCT01009047.

Topics: Adolescent; Antipsychotic Agents; Aripiprazole; Child; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Europe; Female; Headache; Humans; India; Male; Paliperidone Palmitate; Psychiatric Status Rating Scales; Psychomotor Agitation; Schizophrenia; Severity of Illness Index; Treatment Outcome; United States; Weight Gain

To investigate the effect of valproic acid on plasma levels of risperidone and its active metabolite, 9-hydroxyrisperidone under steady state conditions in 12 schizophrenic patients.. The efficacy and tolerability for the combination treatment of valproic acid and risperidone were examined.. The addition of valproic acid to risperidone significantly reduced total scores of PANSS positive symptoms, especially excitement and hostility scores, but did not change SAS scores. Addition of valproic acid did not alter plasma concentrations of risperidone or 9-hydroxyrisperidone or active moiety, and the risperidone/9-hydroxyrisperidone ratio. The combination of valproic acid with risperidone decreased plasma levels of HVA, but not those of MHPG; additionally, treatment with this combination was found to reduce dopaminergic activity.. These results suggest that the addition of valproic acid to risperidone is both effective and well tolerated for treating excitement and impulsiveness in schizophrenic patients without influencing the metabolism of risperidone, and treatment with valproic acid and risperidone.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Drug Interactions; Female; Homovanillic Acid; Humans; Isoxazoles; Male; Methoxyhydroxyphenylglycol; Middle Aged; Paliperidone Palmitate; Psychiatric Status Rating Scales; Psychomotor Agitation; Pyrimidines; Risperidone; Schizophrenia; Schizophrenic Psychology; Valproic Acid