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.

Abstract

We investigated changes in brain intracortical myelin (ICM) volume in the frontal lobe after 9months of treatment with paliperidone palmitate (PP) compared with 9months 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. 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, 9months 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. 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). In participants with recent-onset schizophrenia or schizophreniform disorder, frontal ICM volume was preserved at baseline levels in those treated with PP over 9months. However, a decrease of frontal ICM volume was observed among participants treated with OAPs. clinicaltrials.gov identifier NCT02431702.