A Randomized, Double-Blind, Multicenter, Noninferiority Study Comparing Paliperidone Palmitate 6-Month Versus the 3-Month Long-Acting Injectable in Patients With Schizophrenia.

BACKGROUND: This double-blind (DB), randomized, parallel-group study was designed to evaluate efficacy and safety of paliperidone palmitate 6-month (PP6M) formulation relative to paliperidone palmitate 3-month (PP3M) formulation in patients with schizophrenia. METHODS: Following screening, patients entered an open-label (OL) maintenance phase and received 1 injection cycle of paliperidone palmitate 1-month (PP1M; 100 or 150 mg eq.) or PP3M (350 or 525 mg eq.). Clinically stable patients were randomized (2:1) to receive PP6M (700 or 1000 mg eq., gluteal injections) or PP3M (350 or 525 mg eq.) in a 12-month DB phase; 2 doses of PP6M (corresponding to doses of PP1M and PP3M) were chosen. RESULTS: Overall, 1036 patients were screened, 838 entered the OL phase, and 702 (mean age: 40.8 years) were randomized (PP6M: 478; PP3M: 224); 618 (88.0%) patients completed the DB phase (PP6M: 416 [87.0%]; PP3M: 202 [90.2%]). Relapse rates were PP6M, 7.5% (n = 36) and PP3M, 4.9% (n = 11). The Kaplan-Meier estimate of the difference (95% CI) between treatment groups (PP6M - PP3M) in the percentages of patients who remained relapse free was -2.9% (-6.8%, 1.1%), thus meeting noninferiority criteria (95% CI lower bound is larger than the pre-specified noninferiority margin of -10%). Secondary efficacy endpoints corroborated the primary analysis. Incidences of treatment-emergent adverse events were similar between PP6M (62.1%) and PP3M (58.5%). No new safety concerns emerged. CONCLUSIONS: The efficacy of a twice-yearly dosing regimen of PP6M was noninferior to that of PP3M in preventing relapse in patients with schizophrenia adequately treated with PP1M or PP3M. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT03345342.

Impact of risperidone versus haloperidol on activities of daily living in the treatment of refractory schizophrenia.

Risperidone has been shown to improve verbal working memory, executive functioning, attention, reaction time, and verbal learning, which, in turn, have been associated with improved functional outcomes. We tested whether risperidone was associated with greater improvements than haloperidol in activities of daily living (ADLs) among persons having treatment-refractory schizophrenia. In a double-blind, controlled trial of fixed and flexible doses of haloperidol and risperidone, changes in ADLs were operationally monitored on a behavior therapy unit of a state hospital. While no differential effects were noted between risperidone and haloperidol in ADLS, these self-care skills significantly improved as subjects spent longer times on the behavior therapy unit. Working memory and verbal learning did correlate with improvements in ADLs, independent of drug condition. The contingencies of reinforcement and specific training programs on the behavior therapy unit may have been prepotent for the learning of ADLs, obscuring any differential impact of risperidone. Moreover, ADLs may be governed more by "procedural" learning than by working memory or verbal learning, with the former not differentially influenced by typical verus atypical antipsychotics.