Effect of treatment with paliperidone palmitate versus oral antipsychotics on frontal lobe intracortical myelin volume in participants with recent-onset schizophrenia: Magnetic resonance imaging results from the DREaM study.

OBJECTIVE: We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9 months of treatment with paliperidone palmitate (PP) compared with 9 months of treatment with oral antipsychotics (OAP) in participants with recent-onset schizophrenia or schizophreniform disorder from the Disease Recovery Evaluation and Modification (DREaM) study, a randomized, open-label, delayed-start trial. METHODS: DREaM included 3 phases: Part I, a 2-month oral run-in; Part II, a 9-month disease progression phase (PP or OAP); and Part III, 9 months of additional treatment (participants receiving PP continued PP [PP/PP] and participants receiving OAP were rerandomized to receive either PP [OAP/PP] or OAP [OAP/OAP]). In Part II, magnetic resonance imaging (MRI) and functional and symptomatic assessment was performed at baseline, day 92, and day 260. ICM volume as a fraction of the entire brain volume was quantified by subtraction of a proton density image from an inversion recovery image. Within-treatment-group changes from baseline were assessed by paired t-tests. Analysis of covariance was used to analyze ICM volume changes between treatment groups, adjusting for country. RESULTS: The MRI analysis sample size included 71 DREaM participants (PP, 23; OAP, 48) and 64 healthy controls. At baseline, mean adjusted ICM fraction values did not differ between groups (PP, 0.057; OAP, 0.058, p = 0.79). By day 92, the adjusted ICM fraction in the OAP group had decreased significantly (change from baseline, -0.002; p = 0.001), whereas the adjusted ICM fraction remained unchanged from baseline in the PP group (0.000; p = 0.80). At day 260, the change from baseline in adjusted ICM fraction was -0.004 (p = 0.004) in the OAP group and -0.001 (p = 0.728) in the PP group. The difference between treatment groups did not reach statistical significance (p = 0.147). CONCLUSIONS: In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9 months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT02431702.

Paliperidone extended-release for schizophrenia: effects on symptoms and functioning in acutely ill patients with negative symptoms.

BACKGROUND: Most patients with schizophrenia exhibit negative symptoms, even during acute episodes. These difficult-to-treat symptoms are often associated with poor functioning and outcomes. METHODS: A post-hoc analysis of pooled data from three 6-week double-blind studies included patients in an acute episode of schizophrenia who received paliperidone extended-release (ER) (3, 6, 9, or 12 mg) or placebo. Based on criteria developed by the authors, patients were stratified by the presence or absence of predominant negative symptoms at baseline (>or=40% of the maximum negative factor score and <40% of the maximum positive factor score on the Positive and Negative Syndrome Scale [PANSS]). RESULTS: Although these studies were not designed to examine patients with predominant negative symptoms, the criteria identified 23% of acutely ill patients (270/1193). The mean (SD) baseline PANSS negative symptoms factor score, 27.4 (3.3), was 49% of the maximum; the positive symptoms factor score, 23.7 (2.8), was 33% of the maximum. Completion rates with paliperidone ER (n=195) and placebo (n=75) were 64.6% and 44.0%, respectively. Greater improvements occurred with paliperidone ER vs placebo on PANSS (total, negative and other factors), Clinical Global Impressions-Severity and Personal and Social Performance scores at endpoint (all P values <0.05). Adverse events reported in >or=10% of patients were (paliperidone ER vs placebo): headache (14.4% vs 6.7%), insomnia (13.8% vs 21.3%) and sinus tachycardia (10.3% vs 1.3%). Paliperidone ER treatment was associated with a similar response profile in patients without predominant negative symptoms (paliperidone ER, n=647; placebo, n=276). CONCLUSIONS: Schizophrenia patients with predominant negative symptoms were identified in a population of acutely ill patients. Findings of this post-hoc analysis suggest that acutely ill patients with or without predominant negative symptoms respond similarly to treatment with paliperidone ER. No unexpected tolerability findings were observed.