paliperidone

The relationship of LAI paliperidone and LAI aripiprazole plasma levels to their efficacy and tolerability: data from EULAST.

Ustohal Libor L, Obdržálková Marie M, Jáni Martin M, Horská Kateřina K

Poor adherence in schizophrenia is often solved by long-acting injectable (LAI) medication. Even LAIs need to be individualised through dosing adjustments to ensure efficacy and safety. It can be achieved by implementing therapeutic drug monitoring (TDM). That's why we decided to analyse data from the EULAST study. Data from 180 patients who were randomised to one of the LAI groups were used in this study. Their plasma levels at the beginning, throughout and at the end of the study were analysed, and their relationships with efficacy, extrapyramidal side effects, functional status and quality of life were assessed. At the beginning, a significant number (56.1%) of all patients had subtherapeutic plasma levels, during the study 41% of patients had subtherapeutic plasma levels, and at the end, 26.7%. Only a minimum of patients had supratherapeutic plasma levels. No substantial evidence for the relationship between LAI type, plasma level range and treatment outcomes, including efficacy, side effects, functional status and quality of life, was found. Our data did not confirm the impact of LAIs' plasma levels on treatment outcomes. It seems beneficial to revise and reconsider the therapeutic reference range for LAIs; however, further studies are needed.

Structural brain age trajectories in antipsychotic-naive first episode psychosis.

Roig-Herrero Alejandro A, Francey Shona M SM, O'Donoghue Brian B, Nelson Barnaby B et al.

Psychotic disorders such as schizophrenia have been associated with older-appearing brain structure, commonly quantified using the brain-age paradigm. However, it remains unclear whether these alterations are present at illness onset and whether antipsychotic treatment modifies their trajectory. In this study, 61 (28 females and 33 males) antipsychotic-naïve people with first-episode psychosis were randomized to receive either a second-generation antipsychotic (risperidone or paliperidone) or placebo over a 6-month treatment period, alongside intensive psychosocial therapy. A healthy control group (n = 27, 17 females, 10 males) was also recruited. Structural MRI scans were collected at baseline, 3 months, and 12 months. Brain age was estimated using two pretrained and validated models (Pyment and CentileBrain). Brain-predicted age difference (brain-PAD) did not differ between patients and healthy controls at baseline (F(1,80) = 0.81, p = 0.37). There were also no significant effects of time, treatment group (antipsychotic, placebo, healthy control), or their interaction on brain-PAD across the first year (all p > 0.26). Findings were consistent across both brain-age models, and brain-PAD was not associated with clinical and lifestyle measures. These findings suggest that altered structural brain aging is not evident during the earliest stages of psychosis and is not modified by early antipsychotic exposure over the first year of illness. Longer follow-up and approaches that account for illness heterogeneity may be needed to clarify when brain-age alterations emerge in psychotic disorders. Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/; ACTRN12607000608460).

Six-Monthly Formulation of Paliperidone Palmitate in Delusional Disorder: First Case Report.

Cunha Mário Jorge Martins Rodrigues da MJMRD, Velosa Ana Patrícia Santos APS

Effects of Second-Generation Long-Acting Injectable Antipsychotics on Brain Structure in Schizophrenia: A Systematic Review of Neuroimaging Studies.

Martiadis Vassilis V, Scognamiglio Pasquale P, Raffone Fabiola F, Olivola Miriam M et al.

Background/Objectives: Second-generation long-acting injectable antipsychotics (SGA-LAIs) are increasingly used to improve adherence and prevent relapse in patients suffering from schizophrenia. Beyond clinical efficacy, growing attention is being paid to their potential impact on brain structure. This systematic review aims to synthesize available evidence from neuroimaging studies investigating the effects of SGA-LAIs on grey matter (GM) and white matter (WM) in individuals with schizophrenia. Methods: A systematic search of PubMed/MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials was run from database inception to 13 August 2026, supplemented by Google Scholar, trial registries, and backward and forward citation tracking of the included studies. Eligible studies were original reports assessing the effects of SGA-LAIs on brain structure or brain function with magnetic resonance imaging (MRI) in patients with schizophrenia. Study selection followed the PRISMA 2020 statement, and data extraction focused on sample characteristics, treatment, imaging outcomes, and main findings. Risk of bias was appraised with RoB 2 and ROBINS-I. Results: Of 687 unique records screened, nine studies met the inclusion criteria. The evidence base is narrow: the nine studies correspond to only five independent samples, with six of them acquiring both a baseline and a follow-up scan and five providing a randomized comparison with oral antipsychotics, and the only molecules studied were risperidone LAI and paliperidone palmitate. Five randomized reports compared an SGA-LAI with oral antipsychotics and described better preservation of intracortical myelin and of cortical thickness with the long-acting formulation, most often in frontal regions, although the between-group difference reached statistical significance in only two of them and diffusion measures in one cohort moved in the opposite direction. Two cross-sectional functional MRI studies comparing risperidone LAI with first-generation depot medication described activation patterns closer to those of healthy controls in the LAI group, and one longitudinal resting-state study documented changes in regional homogeneity during paliperidone palmitate treatment. In some cases, structural or functional changes correlated with clinical or cognitive improvement. However, all included studies were judged to be at high or serious risk of bias, and the nine studies correspond to only five independent samples, so that the apparent convergence of findings partly reflects repeated analyses of the same participants; the limited number of studies and their methodological heterogeneity prevent firm generalizations. Conclusions: Preliminary and low-certainty evidence suggests that SGA-LAIs may be associated with better preservation of intracortical myelin and cortical thickness in schizophrenia, with convergent but weaker functional data and with diffusion findings that do not fit this reading. These results are hypothesis-generating and do not establish a neuroprotective effect. Larger and independent longitudinal studies with standardized imaging protocols and prespecified clinical endpoints are needed before any structural advantage of LAI formulations can be considered established.