Persistence and adherence to second-generation antipsychotic long-acting injectable medications for schizophrenia: A comparative study in the Australian context.

OBJECTIVE: To examine patient characteristics, persistence and adherence to treatment associated with use of second-generation antipsychotic long-acting injectable (SGA LAI) medications in the Australian real-world setting. METHOD: Five SGA LAIs were compared using a retrospective 10% sample of prescriptions in Australian Pharmaceutical Benefits Scheme (PBS) data: paliperidone palmitate 1-monthly (PP1M), paliperidone palmitate 3-monthly (PP3M), aripiprazole monohydrate (ARI), risperidone (RLAI) and olanzapine pamoate (OLAI). RESULTS: Patients in the PP3M cohort were more persistent with treatment (p < 0.001). Median months of persistence: PP3M (36 months); ARI (18 months); PP1M (11 months); OLAI (8 months); RLAI (4 months). Patients in the PP3M cohort were more adherent to treatment (p < 0.001): PP3M (78%); ARI (51%); PP1M (46%); OLAI (35%); RLAI (33%). CONCLUSIONS: Patients on PP3M treatment showed comparatively longer persistence and better adherence. Treatments for schizophrenia with longer dosing intervals may provide patients with symptomatic stability that could allow for reduced hospitalisations/relapse and increased focus on functional recovery.

Novel PPAR-gamma agonists identified from a natural product library: a virtual screening, induced-fit docking and biological assay study.

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays an essential role in lipid and glucose homeostasis. It is recognized as the receptor of the thiazolidinediones-a synthetic class of anti-diabetic drugs-and is the target of many drug discovery efforts because of its role in disease states, such as type II diabetes mellitus. In this study, structure-based virtual screening of the PPAR-gamma ligand binding domain against a natural product library has revealed 29 potential agonists. In vitro testing of this list identified six flavonoids to have stimulated PPAR-gamma transcriptional activity in a transcriptional factor assay. Of these, flavonoid-psi-baptigenin-was classed as the most potent PPAR-gamma agonist, possessing low micromolar affinity (EC(50) = 2.9 microM). Further in vitro testing using quantitative RT-PCR and immunoblotting experiments demonstrated that psi-baptigenin activated PPAR-gamma mRNA (4.1 +/- 0.2-fold) and protein levels (2.9 +/- 0.4-fold) in THP-1 macrophages. Moreover, psi-baptigenin's-induced PPAR-gamma enhancement was abolished in the presence of a selective PPAR-gamma antagonist, GW9662. Induced-fit docking investigations provide a detailed understanding on the ligands' mechanism of action, suggesting five of the active flavonoids induce significant conformational change in the receptor upon binding. Overall, these results offer insight into various naturally derived flavonoids as leads/templates for development of novel PPAR-gamma ligands.