We evaluated the efficacy of paliperidone extended-release (ER), an investigational psychotropic agent, in delaying symptom recurrence in adult patients with schizophrenia and its safety and tolerability. In this randomized, double-blind, placebo-controlled, multicenter study, patients' symptoms were stabilized during an 8-week run-in and a 6-week stabilization phases using open-label, flexibly dosed paliperidone ER (3-15 mg once daily, starting dose = 9 mg). The primary efficacy variable was the time of first recurrence of schizophrenia symptoms, which included predefined changes in symptom scores, psychiatric hospitalization, self-injury, and suicidal or aggressive behavior during the double-blind phase (paliperidone ER or placebo treatment). Based on positive efficacy, the study was terminated at the preplanned interim analysis (43 recurrence events). The interim analysis (primary analysis) included 113 patients (mean age = 41 years; 51% men, 85% white). In the intent-to-treat group, 14 paliperidone ER-treated patients (25%) experienced a recurrence event versus 29 (53%) for placebo. Time-to-recurrence was significantly different, favoring the paliperidone ER group (P = 0.005, log-rank test): 25% quantile of time-to-recurrence was 83 days (paliperidone ER) versus 23 days (placebo). Final analyses (n = 205) were confirmatory. During initial open-label treatment with paliperidone ER, symptoms improved significantly. This improvement was maintained with continued treatment, as were functioning and quality-of-life measures. Treatment-emergent adverse events rates were similar: 35% for paliperidone ER and 40% for placebo. Paliperidone ER treatment versus placebo significantly delayed time-to-recurrence in patients with schizophrenia, maintained symptom stability and measures of functioning, and was generally well tolerated in this patient population.

Objective:  To evaluate the efficacy and tolerability of topiramate monotherapy in adults with acute manic or mixed episodes of bipolar I disorder. Methods:  In four trials, adults hospitalized with acute mania, a diagnosis of bipolar I disorder, history of ≥1 previous manic or mixed episodes, and ≥20 Young Mania Rating Scale (YMRS) score were randomized to double‐blind treatment with topiramate (target doses: 200, 400, or 600 mg/day) or placebo; two trials included an active comparator (lithium, 1500 mg/day). The core study duration in all trials was 3 weeks; three trials also had 9‐week double‐blind extensions. The primary efficacy variable was mean change from baseline in YMRS in the core 3‐week study. Results:  Changes in YMRS score during 3 weeks were not significantly different for topiramate versus placebo (mean YMRS reductions, −5.1 to −8.4). Mean YMRS reductions in lithium‐treated groups were significantly greater (p ≤ 0.001 versus placebo and topiramate). A similar pattern was observed after 12 weeks of double‐blind treatment in studies with double‐blind extensions. Paresthesia, appetite decrease, dry mouth, and weight loss were more frequently associated with topiramate than with placebo. Conclusions:  These studies do not support the efficacy of topiramate as monotherapy in acute mania or mixed episodes in adults with bipolar I disorder. Topiramate was not associated with mood destabilization measured as mania exacerbation or treatment‐emergent depression. Lithium was confirmed as an effective therapy in this population.

Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to <45 kg], 0.175 mg/day [>45 kg] or high-dose: 1.25 mg/day [20 to <45 kg], 1.75 mg/day [>45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change in Aberrant Behavior Checklist-Irritability (primary endpoint) was significantly greater in the high-dose-(-12.4 [6.5]; p < 0.001), but not low-dose (-7.4 [8.1]; p = 0.164) group, versus placebo (-3.5 [10.7]). Clinical Global Impressions-Severity and Children's Yale-Brown Obsessive Compulsive Scale scores improved significantly only in the high-dose group, consistent with ABC-I results. Somnolence, sedation and increased appetite occurred more frequently in high-versus low-dose groups. Overall, increased appetite occurred most frequently.

No abstract

At daily doses of 0.5-2.5 mg and 3-6 mg, risperidone was effective and well tolerated in children and adolescents experiencing acute manic or mixed episodes of bipolar I disorder. Results indicate that risperidone 0.5-2.5 mg has a better benefit-risk profile than risperidone 3-6 mg.