Agomelatine for Depression in Schizophrenia: A Case-Series

Objectives

Agomelatine, a melatonin (MT1/MT2) receptor agonist and 5-HT2C receptor antagonist, is a new antidepressant and a potential therapeutic option for major depressive episodes and negative symptoms in persons with schizophrenia. We investigated such treatment outcomes with respect to antidepressant efficacy, safety, and tolerability.

Methods

We report a consecutive case series of seven patients with schizophrenia and comorbid major depressive symptoms who received agomelatine for a period of at least six weeks in addition to stable doses of antipsychotic agents. General psychopathology, positive, negative and depressive symptoms were assessed with standardized interviews. Relevant blood parameters were assessed.

Results

Depressive symptoms improved significantly. Positive symptoms remained stable, while negative symptoms and global psychopathology improved significantly. Agomelatine was well tolerated in most patients.

Conclusions

Our findings provide initial evidence that agomelatine is safe and efficacious in treating depressive symptoms in patients with schizophrenia. Furthermore, agomelatine seems to be effective for the treatment of negative symptoms. Randomized controlled trials are necessary to confirm these first observations.     

Exposure to dioxin-like pollutants via different food commodities in Swedish children and young adults

The dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) in terms of toxic equivalents (TEQs) was investigated in Swedish children and young adults. Exposure was estimated from concentration data of six groups of individual food commodities (meat, fish, dairy products, egg, edible fats and other foodstuff) combined with food intake data from a 7-day record book obtained from 670 individuals aged 1–24 years. The results showed that Swedish boys and girls, up to the age of ten, had a median TEQ intake that exceeded the tolerable daily intake (TDI) of 2 pg TEQ/kg body weight. Children exceeding the TDI varied from almost all individuals among the youngest children to about 20% among young men and women. Dairy and fish products were the main sources of exposure for the average child, accounting for 59% of the total TEQ intake. The individuals most highly exposed were, on the other hand, characterized by a high consumption of fish. Since children constitute a vulnerable group, results obtained from the present study show that it is essential to perform age specific dietary intake assessments of pollutants and more carefully consider sensitive and/or highly exposed groups in the population in the risk management processes.     

Internet-based Self-Assessment after the Tsunami: lessons learned

Background  

In the aftermath of the Tsunami disaster in 2004, an online psychological self-assessment (ONSET) was developed and made available by the University of Zurich in order to provide an online screening instrument for Tsunami victims to test if they were traumatized and in need of mental health care. The objective of the study was to report the lessons learnt that were made using an Internet-based, self-screening instrument after a large-scale disaster and to discuss its outreach and usefulness.     

Dietary intake and biomarker status of folate in Swedish adults

Purpose

National data on folate status are missing in Sweden, and regional data indicate folate insufficiency in up to more than 25% of the study populations. The objectives were to determine folate intake and status in the adult Swedish population as well as identifying dietary patterns associated with beneficial folate status.

Methods

Folate intake was estimated using a web-based 4-d food record in adults aged 18–80 years (n = 1797). Folate status was measured as erythrocyte (n = 282) and plasma folate concentrations (n = 294). Factor analysis was used to derive a dietary pattern associated with a higher folate status.

Results

Median folate intake was 246 µg/day (Q ₁ = 196, Q ₃ = 304, n = 1797) and for women of reproductive age 227 µg/day (Q ₁ = 181, Q ₃ = 282, n = 450). As dietary folate equivalents (DFE), median intake was 257 µg/day (Q ₁ = 201, Q ₃ = 323) and for women of reproductive age 239 µg/day (Q ₁ = 185, Q ₃ = 300). Low blood folate concentrations were found in 2% (erythrocyte concentrations <317 nmol/L) and 4% (plasma concentrations <6.8 nmol/L) of the participants, respectively. None of the women of reproductive age had erythrocyte folate concentrations associated with the lowest risk of neural tube defects. Dietary patterns associated with higher folate status were rich in vegetables, pulses and roots as well as cheese and alcoholic beverages, and low in meat.

Conclusions

Prevalence of low erythrocyte folate concentrations was low in this population, and estimated dietary intakes are well above average requirement. However, to obtain a folate status optimal for prevention of neural tube defects major dietary changes are required and folic acid supplements recommended prior to conception.

     

Combination of a hot-melt subcoating and an enteric coating for moisture protection of hygroscopic Sennae fructus tablets

The objective of this study was to investigate the efficiency of moisture protection of hot-melt coatings solely and in combination with an enteric coating on hygroscopic tablet cores containing a spray-dried Sennae fructus extract. Tablet cores were subcoated with different hot-melt coating materials: medium chain tryglycerides, stearic acid, Precirol^® ATO 5, and Compritol^® 888 ATO, at varying amounts and coated with Eudragit^® L 30D-55 for enteric resistance. Subcoating penetration, tablet disintegration, dissolution times, tablet hygroscopicity, and tablet properties such as weight, height, diameter, and hardness were analyzed. 3?mg/cm² of tablet surface seemed to be sufficient if sustained release is not required. Thereby, hot-melt coating did not adversely affect the tablet properties with regard to subsequent processing steps. Compared to the tablet cores it was possible to reduce the moisture uptake by 85% at 75% relative humidity with tablets coated with a combination of Precirol^® ATO 5 and Eudragit^® L 30D-55. This combination was more efficient than high amounts of Eudragit^® L 30D-55. Hot-melt coating proved to be a suitable technique for the application of subcoating material to tablet cores serving as a barrier against water permeation into hygroscopic tablet cores without exceeding the required disintegration times.     

Assessment of dietary cadmium exposure in Sweden and population health concern including scenario analysis

The median dietary cadmium exposure for adults in Sweden is around 1 μg/kg/week and the upper 95th and 99th percentiles are 1.6-1.8 and 1.9-2.2 μg/kg/week, respectively. Potatoes and wheat flour were the most important food categories, contributing with 40-50% to the exposure. Differences in dietary patterns between high and low exposed individuals were observed; for high exposed individuals, seafood and spinach contributed with an exposure similar to that low exposed individuals received from potatoes and wheat flour. Consequences of differences in methodology used for exposure assessment are discussed. The median exposure is a factor 2 lower compared to that estimated by the European Food Safety Authority (EFSA). It is also a factor 1.4 lower compared to that of the assessment used for development of the EFSA tolerable weekly intake (TWI). The potential importance of this latter fact was addressed by adjusting the present assessment to that used for TWI derivation. While the percentage of the population exceeding the TWI was <1% for the present data, it was around 3% for adjusted data, which is more in line with observations at the level of urinary cadmium. Scenario analysis was also performed to addresses the consequence of increasing/decreasing cadmium occurrence levels.     

Teenage pregnancy in developed countries: determinants and policy implications

Because of the high adolescent fertility rates in the US, the Alan Guttmacher Institute (AGI) conducted a 1985 study of adolescent pregnancy and childbearing in 37 developed countries. This was an effort to unveil those factors responsible for determining teenage reproductive behavior. This article presents the data from that study. Birthrates were collected and separated into 2 age groups: for those under 18 and those women 18 to 19 years of age. A 42 variable questionnaire was sent to the public affairs officer of the American embassy and family planning organization in each foreign country to provide additional socioeconomic, behavioral, and educational data. Childbearing was found to be positively correlated with agricultural work, denoting a socioeconomic influence. Adolescent birthrates showed a positive correlation with levels of maternity leaves and benefits offered in the country. The lowest birthrates were found in those countries with the most liberal attitudes toward sex as demonstrated through media representation of female nudity, extent of nudity on public beaches, sales of sexually explicit literature, and media advertising of condoms. A negative correlation was seen for equitable distribution of income and the under 18 birthrate. The older teenage birthrate was found to be lower for countries with higher minimum ages for marriage. They also suggested a responsiveness to government efforts to increase fertility. Some general patterns emerged to explain the high teenage birthrate for the US: it is less open about sexual matters than countries with lower adolescent birthrates and the income in the US is distributed to families of low economic status. A more subtle factor is that although contraception is available, it is not that accessible to young men and women because of the cost. Case studies were presented to provide a more detailed understanding of the reasons for the high adolescent birthrates. Examined are desire for pregnancy, exposure to risk of pregnancy, contraceptive use, access to contraceptive and abortion services, and sex education.     

Neuropeptide Y and somatostatin immunoreactivity in the rat hippocampus after moderate hypoxia

Transient moderate hypoxia has been previously shown to exert a potent protective role to subsequently applied convulsant drugs. We now investigated neuropeptide Y and somatostatin immunoreactivities seven days after moderate hypoxia (9% O₂ in N₂ for two times 8 h) in the hippocampus of the rat. A slight reduction of somatostatin immunoreactive cells was observed in the hilus of the dorsal and ventral hippocampus. At the same time, the total number of neuropeptide Y immunoreactive neurons was increased in this area due to a pronounced increase in staining of presumable basket cells. There was also increased staining of neuropeptide Y positive fibers in the outer molecular layer. Our data suggest activation of neuropeptide Y containing interneurons after a moderate or a mild transient hypoxia. Activation of these inhibitory neurons may contribute to the protective effect of this treatment.     

Seasonal associations between weather conditions and suicide--evidence against a classic hypothesis

Psychiatrists, epidemiologists, and sociologists have debated the existence of an association between weather conditions and suicide seasonality since the preliminary statistical investigations in the 19th century. Provided that the effect of weather conditions on suicide operates via a dose-response-like mechanism, time-series (Box-Jenkins) analysis permits an indirect test of the hypothesis that temperature or other weather variables promote higher suicide frequencies in late spring and early summer months. The authors modeled monthly data on suicide and climatic conditions (i.e., temperature, sunshine, and precipitation data) in Switzerland. Cross-correlations between the filtered (prewhitened) residual series were calculated for the period 1881-2000, for consecutive 30-year periods, for different suicide methods, and--with regard to the seasonality hypothesis--for series relying on moving 1- and 3-month frames. Positive cross-correlations emerged between suicide and temperature data for the whole time series, as well as in all consecutive 30-year periods. However, cross-correlations of data series based on moving frames showed a minor peak in associations for summer frames and a major peak in associations for winter frames, the latter reflecting suicides performed mainly outdoors (being run over by a train and jumping from high places). The results represent a novel minor effect in seasonality of suicide, which is hardly compatible with the hypothesized role of temperature in suicide seasonality.     

Impact of target reproducibility on tumor dose in stereotactic radiotherapy of targets in the lung and liver.

BACKGROUND AND PURPOSE: Previous analyses of target reproducibility in extracranial stereotactic radiotherapy have revealed standard security margins for planning target volume (PTV) definition of 5mm in axial and 5-10mm in longitudinal direction. In this study the reproducibility of the clinical target volume (CTV) of lung and liver tumors within the PTV over the complete course of hypofractionated treatment is evaluated. The impact of target mobility on dose to the CTV is assessed by dose-volume histograms (DVH). MATERIALS AND METHODS: Twenty-two pulmonary and 21 hepatic targets were treated with three stereotactic fractions of 10 Gy to the PTV-enclosing 100%-isodose with normalization to 150% at the isocenter. A conformal dose distribution was related to the PTV, which was defined by margins of 5-10mm added to the CTV. Prior to each fraction a computed tomography (CT)-simulation over the complete target volume was performed resulting in a total of 60 CT-simulations for lung and 58 CT-simulations for hepatic targets. The CTV from each CT-simulation was segmented and matched with the CT-study used for treatment planning. A DVH of the simulated CTV was calculated for each fraction. The target coverage (TC) of dose to the simulated CTV was defined as the proportion of the CTV receiving at least the reference dose (100%). RESULTS: A decrease of TC to <95% was found in 3/60 simulations (5%) of pulmonary and 7/58 simulations (12%) of hepatic targets. In two of 22 pulmonary targets (9%) and in four of 21 hepatic targets (19%) a TC of <95% occurred in at least one fraction. At risk for a decreased TC <95% were pulmonary targets with increased breathing mobility and hepatic targets with a CTV exceeding 100 cm(3). CONCLUSIONS: Target reproducibility was precise within the reference isodose in 91% of lung and 81% of liver tumors with a TC of the complete CTV >or=95% at each fraction of treatment. Pulmonary targets with increased breathing mobility and liver tumors >100 cm(3) are at risk for target deviation exceeding the standard security margins for PTV-definition at least for one fraction and require individual evaluation of sufficient margins.