Aripiprazole for late-life schizophrenia

Antipsychotics are frequently used in elderly patients to treat a variety of conditions, including schizophrenia. While extensively studied for their impact in younger populations, there is comparatively limited evidence about the effectiveness of these agents in older patients. Further complicating this situation are the high co-morbidity rates (both psychiatric and medical) in the elderly; age-related changes in pharmacokinetics leading to a heightened proclivity for adverse effects; and the potential for multiple, clinically relevant drug interactions. With this background in mind, we review diagnostic and treatment-related issues specific to elderly patients suffering from schizophrenia and other psychotic conditions, focusing on the potential role of aripiprazole

Paliperidone ER: a review of the clinical trial data

Paliperidone extended-release tablet (paliperidone ER; INVEGA™) is an oral antipsychotic for the treatment of schizophrenia. The recommended dose range is 3–12 mg per day. Paliperidone ER utilizes the OROS® delivery system, which allows for once-daily dosing. Its pharmacokinetic profile results in a more stable serum concentration. Paliperidone is 9-hydroxyrisperidone, the chief active metabolite of risperidone. It undergoes limited hepatic metabolism, thereby minimizing the risks of hepatic drug–drug and drug–disease interactions. Three 6-week trials in patients with acute schizophrenia reported that paliperidone ER was effective, well tolerated, and produced clinically meaningful improvements in personal and social functioning compared with placebo. Post-hoc analysis of these trials in various populations, including recently diagnosed, elderly and more severely ill patients, those with sleep disturbances and those with predominant negative symptoms demonstrated improvement as well. Paliperidone ER was also significantly better than placebo in the prevention of symptom recurrence in a 6-month maintenance study. The most common clinically relevant adverse events associated with paliperidone ER were extrapyramidal symptoms, tachycardia and somnolence. The incidence of Parkinsonism, akathisia and use of anticholinergic medications increased in a dose-related manner. Further, modest QTc interval prolongation was observed but did not produce clinical symptoms. Similar to risperidone, paliperidone ER is associated with increases in serum prolactin levels. Overall, paliperidone ER was effective, well tolerated and provides a new treatment option for patients with schizophrenia

Can Medication Free, Treatment-Resistant, Depressed Patients Who Initially Respond to TMS Be Maintained Off Medications? A Prospective, 12-Month Multisite Randomized Pilot Study

AbstractBackgroundRepetitive transcranial magnetic stimulation (TMS) is efficacious for acute treatment of resistant major depressive disorder (MDD), but there is little information on maintenance TMS after acute response.Objective/hypothesisThis pilot feasibility study investigated 12-month outcomes comparing two maintenance TMS approaches – a scheduled, single TMS session delivered monthly (SCH) vs. observation only (OBS).MethodsAntidepressant-free patients with unipolar, non-psychotic, treatment-resistant MDD participated in a randomized, open-label, multisite trial. Patients meeting protocol-defined criteria for improvement after six weeks of acute TMS were randomized to SCH or OBS regimens. TMS reintroduction was available for symptomatic worsening; all patients remained antidepressant-free during the trial.ResultsSixty-seven patients enrolled in the acute phase, and 49 (73%) met randomization criteria. Groups were matched, although more patients in the SCH group had failed ≥2 antidepressants (p = .035). There were no significant group differences on any outcome measure. SCH patients had nonsignificantly longer time to first TMS reintroduction, 91 ± 66 days, vs. OBS, 77 ± 52 days; OBS patients were nonsignificantly more likely to need reintroduction (odds ratio = 1.21, 95% CI .38–3.89). Reintroduction lasted 14.3 ± 17.8 days (SCH) and 16.9 ± 18.9 days (OBS); 14/18 (78%) SCH and 17/27 (63%) OBS responded to reintroduction. Sixteen patients (32.7%) completed all 53 weeks of the study.ConclusionsMaintaining treatment-resistant depressed patients off medications with periodic TMS appears feasible in some cases. There was no statistical advantage of SCH vs. OBS, although SCH was associated with a nonsignificantly longer time to relapse. Those who initially respond to TMS have a strong chance of re-responding if relapse occurs

Predicting hospital admission and discharge with symptom or function scores in patients with schizophrenia: pooled analysis of a clinical trial extension

<p>Abstract</p> <p>Background</p> <p>The purpose of this analysis was to evaluate relationships between hospital admission or discharge and scores for symptom or functioning in patients with schizophrenia.</p> <p>Methods</p> <p>Data were from three 52-week open-label extensions of the double-blind pivotal trials of paliperidone extended-release (ER). Symptoms and patient function were measured every 4 weeks using the Personal and Social Performance (PSP) scale and the Positive and Negative Syndrome Scale (PANSS). The intent-to-treat analysis set was defined as open-label patients who had at least one post-baseline PSP and PANSS measurement. Time until first hospitalization was evaluated using the Cox proportional hazard model with categorical time-dependent measures for the PSP (1 to 30, 31 to 70, 71 to 100) or PANSS (< 75, ≥ 75 to < 95, ≥ 95), as well as age, gender, schizophrenia duration, and country. Similar analyses were performed for time to discharge.</p> <p>Results</p> <p>Of the 1,077 enrolled patients, 1,028 (95.5%) met study criteria; of these, 382 (37.2%) were hospitalized at open-label baseline. Compared with patients with PSP ≥ 71 group, the hazard for new hospitalization was 8.351 times greater (<it>P </it>= 0.0001) for patients with the poorest functioning (PSP 1 to 30) and 1.977 times greater (<it>P </it>= 0.0295) for patients with PSP of 31-70 compared to the ≥ 71 group. The hazard for new hospitalization was 5.457 times greater (<it>P </it>< 0.0001) for patients PANSS ≥ 95 and 2.316 times greater (<it>P </it>= 0.0027) for the ≥ 75 to < 95 group compared with the < 75 group. For patients hospitalized at baseline, the PANSS ≥ 95 patients had a discharge hazard that was 0.456 times lower than for the < 75 patients (<it>P </it>< 0.0001). The hazard for discharge was 0.646 times lower (<it>P = </it>0.0012) for the PANSS ≥ 75 to < 95 group compared with the < 75 group. A patient's country was a significant predictor variable, with US patients being admitted and discharged faster.</p> <p>Conclusions</p> <p>Better functioning or being less symptomatic is associated with reduced risk for hospitalization and greater chance for early discharge. Treatments or programs that reduce symptoms or improve function decrease the risk of hospitalization in community patients or increase the chance of discharge for hospitalized patients.</p

Improving the Performance in Occupational Health and Safety Management in the Electric Sector: An Integrated Methodology Using Fuzzy Multicriteria Approach

The electric sector is fundamental for the economic and social development of society, impacting on essential aspects such as health, education, employment generation, industrial production, and the provision of various services. In addition to the above, the growing trend in energy consumption worldwide could increase, according to expert estimates, up to 40% by 2030, which in turn increases the efforts of the public and private sector to meet increasing demands and increase access to energy services under requirements of reliability and quality. However, the electricity sector presents challenges and complexities, one of which is the reduction of health and safety risks for workers, service users, and other stakeholders. In many countries, this sector is classified as high risk in occupational safety and health, due to its complexity and the impact of accidents and occupational diseases on the health of workers, in infrastructure, in operating costs and competitiveness of the energy sector. Worldwide, there are rigorous regulations for the electricity sector, from local and national government regulations to international standards to guarantee health and safety conditions. However, it is necessary to develop objective and comprehensive methodologies for evaluating occupational safety and health performance that provides solutions for the electricity sector, not only to comply with standards and regulations also as a continuous improvement tool that supports the decision-making processes given the complexity of the industry and the multiple criteria that are taken into account when evaluating and establishing improvement strategies. In scientific literature, different studies focus on the analysis of accident statistics, the factors that affect accidents and occupational diseases, and the risk assessment of the sector. Despite these considerations, studies that focus directly on the development of hybrid methodologies for the evaluation and improvement of performance in occupational safety and health in the electrical sector, under multiple criteria and uncertainty are mostly limited. Therefore, this document presents an integrated methodology for improving the performance in occupational health and safety in the electric sector through the application of two techniques of Multi-criteria Decision Methods (MCDM) uses in environments under uncertainly. First, the fuzzy Analytic Hierarchy Process (FAHP) is applied to estimate the initial relative weights of criteria and sub-criteria. The fuzzy set theory is incorporated to represent the uncertainty of decision-makers’ preferences. Then, the Decision-making Trial and Evaluation Laboratory (DEMATEL) used for evaluating the interrelations and feedback among criteria and sub-criteria. FAHP and DEMATEL are later combined for calculating the final criteria and sub-criteria weights under vagueness and interdependence. Subsequently, we applied the proposed methodology in a company of the energy sector for diagnosis of performance in OHS to establish improvement proposals, the work path, and implementation costs. Finally, we evaluate the impact of the strategies applied in the improvement of the performance of the company

Meta-Review of Metanalytic Studies with Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Major Depression

BACKGROUND: Major Depression (MD) and treatment-resistant depression (TRD) are worldwide leading causes of disability and therapeutic strategies for these impairing and prevalent conditions include pharmacological augmentation strategies and brain stimulation techniques. In this perspective, repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique with a favorable profile of tolerability which, despite being recently approved by the Food and Drug Administration (FDA) for the treatment of patients with medication-refractory unipolar depression, still raises some doubts about most effective parameters of stimulation.METHODS: A literature search was performed using PubMed for the years 2001 through February 2011 in order to review meta-analytic studies assessing efficacy and safety issues for rTMS in depressive disorders. Fifteen meta-analyses were identified and critically discussed in order to provide an updated and comprehensive overview of the topic with specific emphasis on potentially optimal parameters of stimulation.RESULTS: First meta-analyses on the efficacy of rTMS for the treatment of MD and TRD have shown mixed results. On the other hand, more recent meta-analytic studies seem to support the antidepressant efficacy of the technique to a greater extent, also in light of longer periods of stimulation (e.g. > 2 weeks).CONCLUSION: rTMS seems to be an effective and safe brain stimulation technique for the treatment of medication refractory depression. Nevertheless, further studies are needed to better define specific stimulation-related issues, such as duration of treatment as well as durability of effects and predictors of response