Factors associated with expression of extrapyramidal symptoms in users of atypical antipsychotics.

PURPOSE: The aim of this study was to investigate factors associated with the occurrence of extrapyramidal symptoms (EPS) in users of second-generation antipsychotics (SGA). METHODS: Observational cross-sectional study based on a random sample of subjects from three outpatient clinics. Inclusion criteria were age between 18 and 65 years, of both genders, with a diagnosis of schizophrenia and under the use of a single SGA agent. Subjects who had received i.m. long-acting antipsychotics in the past were excluded. The families of eligible patients were contacted by phone and, if willing to participate in the study, a household visit was scheduled. Informed consent was obtained from all study subjects and their next of kin. The risk of EPS associated with sociodemographic, clinical features and medications used was analyzed by logistic regression. RESULTS: The study population consisted of 213 subjects. EPS were observed in 38.0% of subjects. The more commonly used SGA were olanzapine (76, 35.7%), risperidone (74, 34.3%), quetiapine (26, 12.2%), and ziprasidone (23, 10.8%). Among the drugs used as adjunctive therapy for schizophrenia, benzodiazepines were the most prevalent (31.5%), followed by carbamazepine (24.4%) and antidepressants (20.2%). Multivariate analysis showed that the risk of EPS was associated with the use of carbamazepine (odds ratio 3.677, 95% CI 1.627-8.310). We found no evidence that the type of SGA modified the risk of EPS. CONCLUSION: The occurrence of EPS in SGA users is a common finding, with no difference of antipsychotics studied in relation to the risk of extrapyramidal manifestations. The adjunctive use of carbamazepine may predispose the user of SGA to the occurrence of EPS.

Quality of Life and Hormonal, Biochemical, and Anthropometric Profile Between Olanzapine and Risperidone Users.

This cross-sectional study compared quality of life and side effects in 108 users of olanzapine or risperidone suffering schizophrenia and being attended at psychiatric ambulatory services in Rio Grande do Norte, Brazil. Economic, socio-demographic, anthropometric, biochemical, and hormonal variables were compared. The EuroQoL Five-Dimension Scale (EQ-5D) was used to evaluate quality of life, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ(2) test and Student's t test, with a significance level of 5 %.The household incomes of approximately 80 % of patients were <2.0 minimum wages ($678). Anthropometric variables (waist circumference, hip circumference, weight, waist-to-hip ratio) and systolic and diastolic blood pressure were noted among male olanzapine users (all p < 0.05). EQ-5D scores showed that olanzapine use significantly impacted self-help ability (p < 0.001). Risperidone users had a mean quality-adjusted life year value of 1. Mean total Simpson-Angus Scale scores was 0.38 for olanzapine users and 0.11 for risperidone users (p < 0.02). Significant differences in UKU were observed for the following items: asthenia/lassitude/fatigue (higher among olanzapine users, p = 0.02), dystonia (higher among olanzapine users, p = 0.01), tremors (higher among olanzapine users, p = 0.03), gynecomastia (higher among risperidone users, p < 0.02), and ejaculatory dysfunction (higher among risperidone users, p < 0.02). Olanzapine users had impaired quality of life, which can be explained in part by adverse motor, biochemical, and hormonal effects characteristic of metabolic syndrome.

Olmesartan decreased levels of IL-1ß and TNF-α, down-regulated MMP-2, MMP-9, COX-2, RANK/RANKL and up-regulated SOCs-1 in an intestinal mucositis model.

Methotrexate (MTX) is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukaemia and other malignancies. The efficacy of methotrexate is often limited by mucositis and intestinal injury, which are major causes of morbidity in children and adults. The aim of this study was to evaluate the effect of olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pre-treated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX. Small intestinal homogenates were assayed for levels of the IL-1ß, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX + OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and haemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1ß (p<0.001) and TNF-a (p<0.01), and increase anti-inflammatory cytocine IL-10 (p<0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL(p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signalling in an IMM. We also suggest that the beneficial effect of olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytocines.

Carvedilol decrease IL-1ß and TNF-α, inhibits MMP-2, MMP-9, COX-2, and RANKL expression, and up-regulates OPG in a rat model of periodontitis.

Periodontal diseases are initiated primarily by Gram-negative, tooth-associated microbial biofilms that elicit a host response that causes osseous and soft tissue destruction. Carvedilol is a ß-blocker used as a multifunctional neurohormonal antagonist that has been shown to act not only as an anti-oxidant but also as an anti-inflammatory drug. This study evaluated whether Carvedilol exerted a protective role against ligature-induced periodontitis in a rat model and defined how Carvedilol affected metalloproteinases and RANKL/RANK/OPG expression in the context of bone remodeling. Rats were randomly divided into 5 groups (n = 10/group): (1) non-ligated (NL), (2) ligature-only (LO), and (3) ligature plus Carvedilol (1, 5 or 10 mg/kg daily for 10 days). Periodontal tissue was analyzed for histopathlogy and using immunohistochemical analysis characterized the expression profiles of MMP-2, MMP-9, COX-2, and RANKL/RANK/OPG and determined the presence of IL-1ß, IL-10 and TNF-α, myeloperoxidase (MPO), malonaldehyde (MDA) and, glutathione (GSH). MPO activity in the group with periodontal disease was significantly increased compared to the control group (p<0.05). Rats treated with 10 mg/kg Carvedilol presented with significantly reduced MPO and MDA concentrations (p<0.05) in addition to presenting with reduced levels of the pro-inflammatory cytokines IL-1 ß and TNF-α (p<0.05). IL-10 levels in Carvedilol-treated rats remained unaltered. Immunohistochemical analysis demonstrated reduced expression of MMP-2, MMP-9, RANK, RANKL, COX-2, and OPG in rats treated with 10 mg/kg Carvedilol. This study demonstrated that Carvedilol affected bone formation/destruction and anti-inflammatory activity in a rat model of periodontitis.