A double-blind, placebo-controlled treatment trial of citalopram for major depressive disorder in older patients with heart failure: The relevance of the placebo effect and psychological symptoms

Background: Little is known about the treatment of depression in older patients with heart failure. This Study was developed to investigate the effectiveness of antidepressant treatment for major depressive disorder (MDD) in the elderly with heart failure. Methods: We enrolled 72 older outpatients with ejection fraction < 50 and diagnosed with MDD by the structured clinical interview for DSM-IV. Thirty-seven patients, 19 on citalopram and 18 on placebo, initiated an 8-week double-blind treatment phase. Measurements were performed with the 31-item Hamilton Rating Scale for Depression (Ham-D-31), the Montgomery-Asberg rating scale (MADRS) and the Systematic Assessment for Treatment Emergent Effects (SAFTEE). A psychiatrist followed up the patients weekly, performing a consultation for about 20 min to field complaints after the measurements. Results: A trend toward superiority of citalopram over placebo in reducing depression was observed in MADRS scores (15.05 + 9.74 vs 9.44 + 9.25, P = .082) but not on HAM-D scores. The depressive symptomatology significantly decreased in both groups (P < .001). The high rate of placebo response during the double-blind phase (56.3%) led us to conclude the study at the interim analysis with 37 patients. Conclusion: Citalopram treatment of MDD in older patients with heart failure is well-tolerated with low rates of side effects, but was not significantly more effective than placebo in the treatment of depression. Weekly psychiatric follow-up including counseling may contribute to the improvement of depression in this population. Scales weighted on psychological symptoms such as the MADRS are possibly better suited to measure depression severity and improvement in patients with heart failure. (C) 2009 Elsevier Inc. All rights reserved.

Influence of quinidine, fluvoxamine, and ketoconazole on the enantioselective pharmacokinetics of citalopram in rats

Citalopram (CITA) is available as a racemic mixture or as (+)-(S)-CITA. In humans, CITA is metabolized to demethylcitalopram (DCITA) by CYP2C19, CYP2D6, and CYP3A and to didemethylcitalopram by CYP2D6. There are no data regarding the enzymes involved in CITA and DCITA metabolism in rats. The present study investigated the influence of CYP inhibitors on the enantioselective metabolism of CITA in rats. Male Wistar rats (n = 6) received a single dose of 20 mg.kg(-1) CITA after pretreatment with 80 mg.kg(-1) quinidine, 10 mg.kg(-1) fluvoxamine, 50 mg.kg(-1) ketoconazole, or vehicle (control). Blood samples were collected up to 20 h after CITA administration. The CITA and DCITA enantiomers were analyzed by LC-MS/MS using a Chiralcel OD-R column. The kinetic disposition of CITA was enantioselective in rats (AUC(S/R) ratio = 0.4). Coadministration with quinidine resulted in non-enantioselective inhibition of the metabolism of CITA. Coadministration with fluvoxamine or ketoconazole, however, inhibited only the metabolism of (+)-(S)-CITA, but not of (-)-(R)-CITA when the racemic drug was administered to rats.

Omeprazole preferentially inhibits the metabolism of (+)-(S)-citalopram in healthy volunteers

center dot Citalopram (CITA) pharmacokinetics are enantioselective in healthy volunteers and the metabolism of (+)-(S)-CITA to (+)-(S)-DCITA is dependent on CYP2C19. Omeprazole is a potent CYP2C19 inhibitor. WHAT THIS STUDY ADDS center dot This study indicates that omeprazole induces a loss of enantioselectivity in the CITA pharmacokinetics because of the selective inhibition of (+)-(S)-CITA metabolism. AIM The study assessed the influence of omeprazole on the kinetic disposition of the (+)-(S)-citalopram (CITA) and (-)-(R)-CITA enantiomers in healthy volunteers. METHODS In a cross-over study, healthy volunteers (n = 9) phenotyped as extensive metabolizers of CYP2C19 and CYP2D6 and with an oral midazolam clearance ranging from 10.9 to 149.3 ml min-1 kg-1 received a single dose of racemic CITA (20 mg orally) in combination or not with omeprazole (20 mg day-1 for 18 days). Serial blood samples were collected up to 240 h after CITA administration. CITA and demethylcitalopram (DCITA) enantiomers were analyzed by LC-MS/MS using a Chiralcel (R) OD-R column. RESULTS The kinetic disposition of CITA was enantioselective in the absence of treatment with omeprazole, with the observation of a greater proportion of plasma (-)-(R)-CITA [AUC S : R ratio of 0.53 (95% CI 0.41, 0.66) for CITA and 1.08 (95% CI 0.80, 1.76) for DCITA] than (+)-(S)-CITA. Racemic CITA administration to healthy volunteers in combination with omeprazole showed a loss of enantioselectivity in CITA pharmacokinetics with an increase of approximately 120% in plasma (+)-(S)-CITA concentrations [AUC S : R ratio of 0.95 (95% CI 0.72, 1.10) for CITA and 0.95 (95% CI 0.44, 1.72) for DCITA]. CONCLUSIONS The administration of multiple doses of omeprazole preferentially inhibited (+)-(S)-CITA metabolism in healthy volunteers. Although omeprazole increased plasma concentrations of (+)-(S)-CITA by approximately 120%, it is difficult to evaluate the clinical outcome because the range of plasma CITA concentrations related to maximum efficacy and minimum risk of adverse effects has not been established.

M??dulo 1 - ??tica y pr??ctica administrativa en el contexto de las sociedades en proceso de modernizaci??n: curso ??tica y administraci??n p??blica en am??rica latina

Este documento trata de ??tica en el contexto de las sociedades tradicionales, frente al desaf??o del desarrollo econ??mico y social y, sobre todo, de implantaci??n de una gesti??n p??blica moderna; la relevancia de los valores morales y ??ticos en la consolidaci??n de la democracia, de la ciudadan??a y justicia social en las sociedades en desarrollo

Escuela nacional de administraci??n p??blica

La Escuela Nacional de Administraci??n P??blica - ENAP es una fundaci??n p??blica vinculada al Ministerio de Planificaci??n, Presupuesto y Gesti??n. Fundada en 1986, tiene como misi??n principal "desarrollar las competencias de funcionarios p??blicos, con el prop??sito de mejorar la capacidad gubernamental de administrar pol??ticas p??blicas". Para cumplir con su misi??n ofrece un amplio programa de ense??anza y educaci??n continua a los gestores de pol??ticas p??blicas, adem??s del E-Learning (cursos online) y cursos personlizados de acuerdo con los objetivos institucionales y gubernamentales. Los cursos de la ENAP son planeados de acuerdo con las demandas estrat??gicas gubernamentales de inclusi??n social, reducci??n de la pobreza, y desarrollo econ??mico para fortalecer el liderazgo de la democracia sudamericana. El alcance y la diversidad de sus programas reflejan los desaf??os de los grandes cambios en el mercado y ambiente de trabajo, lo que es enfrentado por los actuales 550.000 funcionarios p??blicos y m??s de 7.000.000 funcionarios p??blicos estatales y municipales que hay en Brasil, de acuerdo con el ??ltimo conteo en 2006.

M??dulo 2 - relativismo de valores y universalismo de principios en la pr??ctica administrativa: curso ??tica y administraci??n p??blica en Am??rica Latina

Este trabajo se ocupa de los conceptos de ??tica y moral bajo la perspectiva de los principios y valores que permean la actuaci??n del servidor p??blico en la Administraci??n P??blica; la naturaleza sociocultural de esos conceptos referente a la diversidad de valores y principios universales que puedan ser adoptados en la pr??ctica administrativa

M??dulo 3 - perspectivas y pr??cticas en el incentivo a la consciencia y conducta ??tica en el contexto de la administraci??n p??blica: curso ??tica y administraci??n p??blica en Am??rica Latina

Este trabajo se ocupa de las cuatro grandes perspectivas en que se encuadran las propuestas de refuerzo de la dimensi??n ??tica en la gesti??n p??blica; los l??mites y el alcance de los aspectos ??ticos y legales de la pr??ctica administrativa; instrumentos gerenciales y pr??cticas que ayudan el desarrollo de la consciencia ??tica

??tica y administraci??n p??blica en Am??rica Latina

Este documento trata de ??tica en el contexto de las sociedades tradicionales, frente al desaf??o del desarrollo econ??mico y social y, sobre todo, de implantaci??n de una gesti??n p??blica moderna; la relevancia de los valores morales y ??ticos en la consolidaci??n de la democracia, de la ciudadan??a y justicia social en las sociedades en desarrollo

Static and hydrodynamic monitoring of citalopram based on its electro-oxidation behavior at a glassy-carbon surface

The electrooxidative behavior of citalopram (CTL) in aqueous media was studied by cyclic voltammetry (CV) and square-wave voltammetry (SWV) at a glassy-carbon electrode. The electrochemical behaviour of CTL involves two electrons and two protons in the irreversible and diffusion controlled oxidation of the tertiary amine group. The maximum analytical signal was obtained in a phosphate buffer (pH ¼ 8.2). For analytical purposes, an SWV method and a flow-injection analysis (FIA) system with amperometric detection were developed. The optimised SWV method showed a linear range between 1.10 10 5–1.20 10 4 molL 1, with a limit of detection (LOD) of 9.5 10 6 molL 1. Using the FIA method, a linear range between 2.00 10 6–9.00 10 5 molL 1 and an LODof 1.9 10 6 molL 1 were obtained. The validation of both methods revealed good performance characteristics confirming applicability for the quantification of CTL in several pharmaceutical products.

Electrochemical determination of citalopram by adsorptive stripping voltammetry–determination in pharmaceutical products

The electrochemical behavior of citalopram was studied by square-wave and square-wave adsorptive-stripping voltammetry (SWAdSV). Citalopram can be reduced and accumulated at a mercury drop electrode, with a maximum peak current intensity being obtained at a potential of approximately -1.25V vs. AgCl/Ag, in an aqueous electrolyte solution of pH 12. A SWAdSV method has been developed for the determination of citalopram in pharmaceutical preparations. The method shows a linear range between 1.0x10-7 and 2.0x10-6 mol L-1 with a limit of detection of 5x10-8 mol L-1 for an accumulation time of 30 s. The precision of the method was evaluated by assessing the repeatability and intermediate precision, achieving good relative standard deviations in all cases (≤2.3%). The proposed method was applied to the determination of citalopram in five pharmaceutical products and the results obtained are in good agreement with the labeled values.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Proposta del perfil de competències d'un professional de comunicació a l'administració pública

L’objecte d’aquest estudi és fer la proposta del perfil d’un professional de la comunicació a l’Administració Pública, dins l’àmbit de Barcelona, en funció d’una gestió per competències. A l’Administració Pública es dóna un buit important respecte al concepte de competències, així com en el marc acadèmic estan definides i classificades, en el món laboral, es troben a l’aire, encara no són una realitat, són competències latents. La nostra aportació, és la traducció de les funcions exigides en competències per tal d’intentar unificar el perfil d’un professional de la comunicació a l’Administració Pública.

Disseny i implementació de la web d'administració d'una colla castellera

El principal motor d una colla castellera són els seus propis castellers i per tant, la gestió de la informació referent a aquests és una de les tasques més importants per aconseguir que una colla creixi. Aquest projecte neix de la necessitat d estructurar i ordenar aquesta informació, a més a més de proporcionar les eines necessàries per poder administrar remotament, i de manera senzilla i eficient, totes aquestes dades. Així doncs, amb aquest treball, s ha intentat proveir als diferents equips que formen una colla castellera (junta, tècnica, comunicació), de les eines necessàries per poder realitzar les seves tasques eficientment.

L’ administració local catalana i la seva relació amb el fet religiós

El present treball no pretén aprofundir en la disciplina jurídica del dret eclesiàstic de l’ Estat, ja que en aquest sentit existeixen nombrosos treballs i molt bons que aborden el tema de forma magistral. El principi de llibertat religiosa i de culte que informen el dret eclesiàstic espanyol, atorga als individus i a les col•lectivitats diverses maneres d’ expressar la seva religió, formes que han d’ estar regulades per no topar amb les limitacions que qualsevol dret fonamental es pot trobar, sobretot la llibertat de les altres persones i l’ ordre públic, per això, calia des de les diferents legislacions tant estatal com autonòmica, abordar el tema des d’una òptica objectiva i laica. L’ encarregat de la defensa dels drets i llibertats fonamentals, continguts al títol I de la Constitució espanyola, és el Tribunal Constitucional a través del recurs d’empara, l’ anàlisi d’ algunes sentències d’ aquest Tribunal ens ha acostat a l’ estudi doctrinal dels diferents principis generals i de les seves limitacions. Per altra banda, les administracions més pròximes a la ciutadania són les administracions locals, són elles, a través dels instruments que la llei els hi permet, las qui han d’aplicar el fet religiós en l’ àmbit territorial on despleguen la seva potestat en relació a les matèries pròpies de la seva competència. L'objectiu d'aquest treball, és buscar i relacionar amb quines eines es troben les Entitats Locals, per fer front a la diversitat religiosa i de culte, producte del canvi social que ha generat bàsicament el moviment migratori. La llei, faculta a l’ administració local perquè adopti determinades posicions a través de la seva declaració de voluntat o la seva potestat reglamentaria, dins els límits que la pròpia llei li exigeix. És en aquest marc, on s’ han analitzat els actes administratius, les ordenances i reglaments que poden afectar a la llibertat religiosa o el dret de culte de dues Corporacions locals de la demarcació de Girona. Per últim, fem una reflexió a mode de conclusió, sobre quines actuacions en relació al fet religiós queden sota l’ autonomia local i en quina intensitat una administració local, que no pot imposar més limitacions que les imprescindibles per a preservar els drets fonamentals, pot influir en el fet religiós.