Bartzokis G, Lu PH, Amar CP, Raven EP, Detore NR, Altshuler LL et al. Long acting injection vs oral risperidone in first-episode schizophrenia: differential impact on white matter myelination trajectory. Schizophr Res 132: 35-41

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, The David Geffen School of Medicine at UCLA, Los Angeles, California, United States.
Schizophrenia Research (Impact Factor: 3.92). 07/2011; 132(1):35-41. DOI: 10.1016/j.schres.2011.06.029
Source: PubMed


Imaging and post-mortem studies provide converging evidence that subjects with schizophrenia (SZ) have a dysregulated trajectory of frontal lobe myelination. Prior MRI studies suggested that early in treatment of SZ, antipsychotic medications initially increase frontal lobe white matter (WM) volume, which subsequently declines prematurely in chronic stages of the disease. Insofar as the trajectory of WM decline associated with chronic disease may be due to medication non-adherence, it may be modifiable by long acting injection (LAI) formulations.
Examine the impact of antipsychotic formulation on the myelination trajectory during a randomized six-month trial of LAI risperidone (RLAI) versus oral risperidone (RisO) in first-episode SZ subjects.
Two groups of SZ subjects (RLAI, N=11; and RisO, N=13) that were matched in pre-randomization oral medication exposure and 14 healthy controls (HCs) were prospectively examined. Frontal lobe WM volume was estimated using inversion recovery (IR) MRI images. A brief neuropsychological battery that focused on reaction times was performed at the end of the study.
WM volume change scores.
WM volume remained stable in the RLAI and decreased significantly in the RisO groups resulting in a significant differential treatment effect, while the HC had a WM change intermediate and not significantly different from the two SZ groups. WM increase was associated with faster reaction times in tests involving frontal lobe function.
The results suggest that RLAI may improve the trajectory of myelination in first-episode patients and have a beneficial impact on cognitive performance. Better adherence provided by LAI may underlie the modified trajectory of myelin development. In vivo MRI biomarkers of myelination can help clarify mechanisms of action of treatment interventions.

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    • "Forced treatment, in and of itself, does not improve outcome;26 however, supervised administration of medication in a trusting relationship can be very effective. In this regard, LAI are nearly universally associated with better outcome when compared with oral medications.27–29 "
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    • "Bartzokis et al.31) evaluated the treatment effects of RLAI on frontal lobe white matter volume in first-episode schizophrenia patients. Their randomized 6-month trial using inversion recovery magnetic resonance image image revealed that the frontal lobe white matter volume remained stable in the RLAI group whereas it significantly decreased in the oral risperidone group. "
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    ABSTRACT: Antipsychotic medications are important for the successful management of schizophrenia. Continuous treatment with medication is superior in relapse prevention and non-adherence to antipsychotic medication is associated with a poor clinical outcome. Long-acting injectable antipsychotics (LAIs) that can guarantee adherence to a treatment regimen could be a useful treatment option. With the introduction of second-generation atypical antipsychotics-long acting injection (SGA-LAI), the risks for extrapyramidal adverse events are decreased. The indications for SGA-LAI have been extended from chronic, stabilized patients to acute psychotic patients. Some studies investigated the use of LAI in first-episode schizophrenia patients and raised the possibility of prescribing LAI as a treatment option. However, there is still limited research using LAI in first-episode schizophrenia. More well-designed, randomized, controlled clinical trials using SGA-LAIs in first episode schizophrenia are needed. Additionally, studies on side effects of SGA-LAI in long-term use are required prior to recommending LAI for patients with first episode schizophrenia.
    Clinical Psychopharmacology and Neuroscience 04/2013; 11(1):1-6. DOI:10.9758/cpn.2013.11.1.1
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    • "A recent study by Bartzokis et al. [32] compared RLAI and oral risperidone treatment in subjects with first-episode schizophrenia. The study focused on changes in frontal lobe myelination and cognitive functioning. "
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    08/2012; 2012(33, supplement):560836. DOI:10.1155/2012/560836
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