Impact on intracortical myelination trajectory of long acting injection versus oral risperidone in first-episode schizophrenia

Abstract

Context Imaging and post-mortem studies suggest that frontal lobe intracortical myelination is dysregulated in schizophrenia (SZ). Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe intracortical myelin (ICM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of ICM decline in chronic SZ is due to medication non-adherence or pharmacokinetics, it may be modifiable by long acting injection (LAI) formulations. Objectives Assess the effect of risperidone formulation on the ICM trajectory during a six-month randomized trial of LAI (RLAI) versus oral (RisO) in first-episode SZ subjects. Design Two groups of SZ subjects (RLAI, N=9; and RisO, N=13) matched on pre-randomization oral medication exposure were prospectively examined at baseline and six months later, along with 12 healthy controls (HCs). Frontal lobe ICM volume was assessed using inversion recovery (IR) and proton density (PD) MRI images. Medication adherence was tracked. Main outcome measure ICM volume change scores adjusted for the change in the HCs. Results ICM volume increased significantly (p=.005) in the RLAI and non-significantly (p=.39) in the RisO groups compared to the healthy controls. A differential between-group treatment effect was at a trend level (p=.093). SZ subjects receiving RLAI had better medication adherence and more ICM increases (chi-square p<.05). Conclusions The results suggest that RLAI may promote ICM development in first-episode SZ patients. Better adherence and/or pharmacokinetics provided by LAI may modify the ICM trajectory. In vivo MRI myelination measures can help clarify pharmacotherapeutic mechanisms of action.

Long-Acting Injectable Risperidone for Relapse Prevention and Control of Breakthrough Symptoms After a Recent First Episode of Schizophrenia

“…The superiority of long-acting injectable risperidone extends beyond preventing psychotic symptom return. Use of long-acting injectable risperidone in our first-episode patients also led to better maintenance of intracortical myelination 22 as well as improved cognitive functioning. 23 If this trifecta of improved psychotic symptom control, cognition, and intracortical myelination can be replicated in longer longitudinal studies of patients with a first episode of schizophrenia, it would suggest that the use of long-acting injectable antipsychotics early in schizophrenia can modify the trajectory of the disorder and lead to better long-term outcomes.…”

The Use of Continuous Treatment Versus Placebo or Intermittent Treatment Strategies in Stabilized Patients with Schizophrenia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with First- and Second-Generation Antipsychotics

“…Interesting, mortality was highest in those who were not medicated [138]. Moreover, several MRI studies [139,140] suggest that early in the treatment of schizophrenia, antipsychotic medications, and more specifically some long-acting SGAs, promote frontal lobe white matter volume, and specifically myelination of the lower layers of the cortex. This is important as dysregulation of the normal myelination trajectory may contribute to the functional deterioration and treatment resistance observed in chronic schizophrenia [139].…”

The role of long-acting injectable antipsychotics in schizophrenia: a critical appraisal

“…However, a study carried out in recently diagnosed patients showed that prolonged treatment with the SGA RLAI was associated with stable white matter volume in comparison with a decrease in volume observed in patients treated with the oral formulation of the same molecule [Bartzokis et al 2012]. These data suggest that, by modifying adherence, RLAI may differentially impact myelination and account for the better long-term outcomes compared with oral risperidone.…”