Genotoxic and cytotoxic evaluation of venlafaxine in an acute and a subchronic assay in mouse / Avaliação genotóxica e citotóxica da venlafaxina em ensaio agudo e subcrônico em camundongos

Abstract The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.

Resumo A presente pesquisa foi feita para determinar a capacidade micronuclei e citotóxica do antidepressivo venlafaxina em ensaios agudos e subcrônicos in vivo em camundongos. No primeiro estudo, administramos uma vez 5, 50 e 250 mg/kg do medicamento e incluímos um grupo negativo e um grupo tratado com daunorubicina. As observações foram feitas diariamente durante quatro dias. O ensaio subcrônico durou cinco semanas com administração diária de venlafaxina (1, 5, e 10 mg/kg) mais um grupo negativo e um grupo administrado de imipramina. As observações foram feitas a cada semana. No primeiro ensaio, os resultados não mostraram aumento de eritrócitos policromáticos micronucleados (MNPE), exceto com a dose elevada a 72 h. O efeito citotóxico mais forte foi encontrado com 250 mg/kg a 72 h (um efeito citotóxico de 51% em comparação com o nível médio de controle). No ensaio subcrônico não foi encontrado aumento de MNPE; entretanto, com a dose mais alta, um aumento significativo de eritrócitos normocromáticos micronucleados foi observado nas últimas três semanas (média de 51% em relação ao valor médio de controle). Foi observado um efeito citotóxico com as duas altas doses nas últimas duas semanas (uma diminuição média de 52% em relação ao valor médio de controle dos eritrócitos policromáticos). Os resultados sugerem cautela com a venlafaxina.

Para el abordaje de depresión en adolescentes: guía de práctica clínica / For the management of depression in adolescents: clinical practice guideline

Generar recomendaciones basadas en la mejor evidencia disponible acerca de la entrega de respecto a la pesquisa, diagnóstico y tratamiento de adolescentes con depresión. Adolescentes sospecha o diagnóstico de depresión, que reciben atención en el nivel primario, secundario y terciario de salud en el sector público y privado de salud. Todos los profesionales de salud con responsabilidades en la atención de adolescentes con depresión. Las recomendaciones de esta Guía fueron elaboradas de acuerdo al sistema "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE). Luego de priorizadas las preguntas a responder, se realizó la búsqueda y la síntesis de evidencia, para finalmente generar las recomendaciones a través del juicio del Panel de Expertos.

La depresión: un desafío en la práctica médica general / La depresión: un desafío en la práctica médica general

Asociada o no a una enfermedad orgánica, la depresión tiene gran prevalencia en la práctica médica pero es subdiagnosticada. El trastorno del ánimo suele coexistir con variadas quejas somáticas y dolores crónicos, configurando síndromes mixtos con un diagnóstico diferencial complejo. En este artículo se describen distintas presentaciones clínicas de la depresión en medicina general, con énfasis en los estados depresivos atípicos, depresiones enmascaradas muy relevantes por su frecuencia y consecuencias: depresión posquirúrgica, cuadros dolorosos crónicos como cefaleas o lumbago, la fatiga crónica y la fibromialgia. Solo el reconocimiento y diagnóstico de la depresión subyacente posibilitará la implementación de las adecuadas intervenciones terapéuticas. Se revisan también algunas recomendaciones para el uso de antidepresivos en atención primaria y la eventual consulta psiquiátrica. (AU)

Associated or not with an organic disease, depression has a high prevalence in medical practice but is underdiagnosed. The mood disorder usually coexists with varied somatic complaints and chronic pain, forming mixed syndromes with a complex differential diagnosis. This article describes different clinical presentations of depression in general medicine, with emphasis on atypical depressive states, masked depressions very relevant for their frequency and consequences: post-surgical depression, chronic painful conditions such as headaches or lumbago, chronic fatigue and fibromyalgia. Only the recognition and diagnosis of the underlying depression will enable the implementation of appropriate therapeutic interventions. Some recommendations for the use of antidepressant drugs in primary care and the eventual psychiatric consultation are also reviewed. (AU)

Effects of in vitro amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts

Abstract Objective: In this study, we aimed to examine the effects of amitriptyline, fluoxetine, tranylcypromine and venlafaxine on saphenous vein grafts in coronary artery bypass graft surgeries. Methods: 59 patients (40 males and 19 females; mean age 65.1 years, distribution: 45-84 years) who had coronary artery bypass graft surgery between February 2014 and May 2016 were included in the study. After the saphenous vein grafts with intact and denuded endothelium were precontracted with 3×10-6M phenylephrine, amitriptyline, fluoxetine and tranylcypromine were cumulatively added to isolated organ baths in the range of 10-11-3x10-5M, while venlafaxine was added in the range of 10-9-3×10-5M. Then, the antidepressant-induced relaxation responses were recorded isometrically. Results: While the relaxation response of amitriptyline at -6.42 (Log M) was 74.6%, the response at -6.32 (Log M) was 75.5%. While the relaxation response at -6.46 (Log M) of fluoxetine was 68.02%, the response at -6.02 (Log M) was 72.12%. While the relaxation response of tranylcypromine at -7.53 (Log M) was 61.13%, the response at -7.23 (Log M) was 65.53%. While the relaxation response of venlafaxine at -6.21 (Log M) was 29.98%, the response at -5.90 (Log M) was 32.96%. Conclusion: The maximum relaxation at minimum and maximum therapeutic concentrations was obtained with amitriptyline, fluoxetine and tranylcypromine, and the minimum relaxation was obtained with venlafaxine. The relaxation responses were independent of the endothelium.

Therapeutic effect of the combined treatment with acupuncture and venlafaxine hydrochloride on depression based on diffusion tensor imaging technology / 中国针灸

OBJECTIVE@#To explore the effectiveness and safety of the combined treatment with acupuncture and venlafaxine hydrochloride on depression in terms of the microstructure change of white matter fiber tracts of brain based on diffusion tensor imaging technology (DTI).@*METHODS@#The prospective study design was adopted. All of 60 patients with depression were randomized into an acupuncture-medication group and a medication group, 30 cases in each one. In the medication group, venlafaxine hydrochloride was used, 75 mg per day in the 1st week, 150 mg per day in the 2nd week and 225 mg per day from the 3rd to 6th week. In the acupuncture-medication group, on the base of the treatment in the medication group, acupuncture was combined. Baihui (GV 20) and Yintang (GV 29) were the main acupoints. The supplementary acupoints were selected according to the clinical symptoms of individuals. The needles were retained for 30 min. Acupuncture was provided once every 2 days, 3 times a week. The consecutive 12 weeks of treatment were required in the two groups. Additionally, a normal group was prepared with 30 healthy volunteers. Separately, before treatment, in 2, 8 and 12 weeks of treatment, Hamilton's depression scale (HAMD-17), Beck depression inventory scale (BDI) and the antidepressant side effect scale (SERS) were adopted to evaluate the effectiveness and safety of the two groups. Moreover, before and after 12 weeks of treatment, DTI was adopted to detect the fractional anisotropy score (FA) of each brain region in the patients.@*RESULTS@#After treatment, the scores of HAMD-17 and BDI were all reduced in the two groups (0.05). Compared with the healthy volunteers, FA scores in 6 brain regions changed obviously in the patients with depression, including the white matter of bilateral frontal lobes, splenium of corpus callosum, left cingulated gyrus, white matter of bilateral inferior temporal gyrus, white matter of bilateral inferior parietal lobe and white matter of bilateral deep temporal occipital region separately. Before treatment, the differences in FA scores of these 6 brain regions were not significant statistically between the two groups (>0.05). After treatment, FA scores in the white matter of bilateral frontal lobes, white matter of bilateral inferior temporal gyrus and white matter of bilateral deep temporal occipital region in the acupuncture-medication group were all higher than those in the medication group (<0.05).@*CONCLUSION@#Acupuncture repairs the brain white matter fiber tracts in some brain regions to certain extent and the therapeutic effects are enhanced with the adjuvant medication of venlafaxine hydrochloride.

Antidepressants in Spine Surgery: A Systematic Review to Determine Benefits and Risks

Antidepressant drugs can be advantageous in treating psychiatric and non-psychiatric illnesses, including spinal disorders. However, spine surgeons remain unfamiliar with the advantages and disadvantages of the use of antidepressant drugs as a part of the medical management of diseases of the spine. Our review article describes a systematic method using the PubMed/Medline database with a specific set of keywords to identify such benefits and drawbacks based on 17 original relevant articles published between January 2000 and February 2018; this provides the community of spine surgeons with available cumulative evidence contained within two tables illustrating both observational (10 studies; three cross-sectional, three case-control, and four cohort studies) and interventional (seven randomized clinical trials) studies. While tricyclic antidepressants (e.g., amitriptyline) and duloxetine can be effective in the treatment of neuropathic pain caused by root compression, venlafaxine may be more appropriate for patients with spinal cord injury presenting with depression and/or nociceptive pain. Despite the potential associated consequences of a prolonged hospital stay, higher cost, and controversial reports regarding the lowering of bone mineral density in the elderly, antidepressants may improve patient satisfaction and quality of life following surgery, and reduce postoperative pain and risk of delirium. The preoperative treatment of preexisting psychiatric diseases, such as anxiety and depression, can improve outcomes for patients with spinal cord injury-related disabilities; however, a preoperative platelet function assay is advocated prior to major spine surgical procedures to protect against significant intraoperative blood loss, as serotonergic antidepressants (e.g., selective serotonin reuptake inhibitors) and bupropion can increase the likelihood of bleeding intraoperatively due to drug-induced platelet dysfunction. This comprehensive review of this evolving topic can assist spine surgeons in better understanding the benefits and risks of antidepressant drugs to optimize outcomes and avoid potential hazards in a spine surgical setting.

The Effect of Antidepressants on Mesenchymal Stem Cell Differentiation

BACKGROUND: Use of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism. METHODS: Human MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was added, supplemented with five increasing concentrations of amitriptyline (0.001–10 µM), venlafaxine (0.01–25 µM), or fluoxetine (0.001–10 µM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a MTT. RESULTS: We found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival. CONCLUSIONS: This study showed a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.

Korean Guidelines for the Pharmacological Treatment of Social Anxiety Disorder: Initial Treatment Strategies

OBJECTIVE: The aim of the present study was to provide clinical consensus and evidence regarding initial treatment strategies for the pharmacological treatment of social anxiety disorder (SAD) in Korea. METHODS: We prepared a questionnaire to derive a consensus from clinicians regarding their preference for the pharmacological treatment of SAD in Korea. Data regarding medication regimens and psychotropic drugs used during initial treatment, the doses used, and the pharmacological treatment duration were obtained. Responses were obtained from 66 SAD experts, and their opinions were classified into three categories (first-line, second-line, third-line) using a chi-square analysis. RESULTS: Clinicians agreed upon first-line regimens for SAD involving monotherapy with selective serotonin reuptake inhibitors (SSRIs) or the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine, or combined therapy using antidepressants with betablockers or benzodiazepines on a standing or as-needed basis. First-line psychotropic drug choices for initial treatment included the following: escitalopram, paroxetine, sertraline, venlafaxine, and propranolol. The medication dosage used by domestic clinicians was found to be comparable with foreign guidelines. Domestic clinicians tended to make treatment decisions in a shorter amount of time and preferred a similar duration of maintenance treatment for SAD when compared with foreign clinicians. CONCLUSION: This study may provide significant information for developing SAD pharmacotherapy guidelines in Korea, especially in the early stage of treatment.

Evaluation of Overactive Bladder in Male Antidepressant Users: A Prospective Study / 대한배뇨장애요실금학회지

PURPOSE: In this study, we investigated overactive bladder (OAB) functions in male patients who used antidepressant drugs (ADs) that were previously examined in female patients, based on conflicting data in literature regarding the effects of AD on OAB and the differences between male and female urinary system physiologies (anatomical and hormonal). METHODS: The study included 202 male patients (a control group of 90 healthy subjects, and an experimental group of 112 patients taking ADs for different disorders). All the patients completed the overactive bladder-validated 8 (OAB-V8) questionnaire, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and the Beck Depression Inventory (BDS). RESULTS: The OAB-V8, ICIQ-SF, and BDS scores for the antidepressant users were significantly higher than those of the control group. The highest prevalence of OAB symptoms was observed in patients taking venlafaxine (68.2%), and the lowest prevalence was in patients taking sertraline (28.0%). Moreover, the frequency of OAB between the antidepressant groups was statistically significant. The univariate logistic regression analyses showed a significant relationship between the presence of OAB, antidepressant usage, BDS score, and the age of a patient. In the multivariate logistic regression analyses, the association between the presence of OAB and antidepressant usage was statistically significant. CONCLUSIONS: The present study showed that the incidence of OAB and the severity of OAB symptoms increased in males using antidepressants for various disorders. This may have been due to unique pharmacological effects, on a molecular or individual level, of serotonin-norepinephrine reuptake inhibitors.

Paroxetine versus Venlafaxine and Escitalopram in Korean Patients with Major Depressive Disorder: A Randomized, Rater-blinded, Six-week Study

OBJECTIVE: The purpose of this study was to compare the efficacy and safety of escitalopram, paroxetine and venlafaxine in Korean patients with major depressive disorder (MDD). METHODS: A total of 449 Korean MDD patients were recruited in a six-week, randomized, rater-blinded, active-controlled trial and were evenly randomized to paroxetine, venlafaxine, or escitalopram treatment. RESULTS: When comparing the mean difference for the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS) total scores during six weeks, paroxetine (−6.4±0.4, and −5.4±0.4, respectively) was found to be significantly superior to escitalopram (−3.7±0.5 and −3.1±0.4, respectively). Venlafaxine had a significantly lower MADRS total score (−5.4±0.4) than escitalopram. When adjusting baseline variables, the response, according to the MADRS and HDRS scores, in the paroxetine group was greater than that for the escitalopram group (odds ratio [OR]=2.43, 95% confidence interval [CI]=1.42–4.16 for MADRS; and OR=2.32, 95% CI=1.35–3.97 for HDRS) and the venlafaxine group (OR=1.94, 95% CI=1.17–3.21 for MADRS; and OR=1.71, 95% CI=1.03–2.83 for HDRS). Despite that the overall tolerability was high and similar among the three groups, a total of 268 subjects (59.7%) prematurely discontinued treatment, representing the main limitation of the present study. CONCLUSION: Although a low study completion rate limits generalizability, our findings suggest that paroxetine might be superior to escitalopram in Korean MDD patients. Further studies should be conducted to draw a definite conclusion.

Dose Dependent Course of Hyperprolactinemic and Normoprolactinemic Galactorrhea Induced by Venlafaxine

Venlafaxine is a serotonergic and noradrenergic reuptake inhibitor which is used for the treatment of depression. We report a case of galactorrhea in a patient with major depressive disorder after starting treatment with venlafaxine. In particular, we discuss the course of hyper and normoprolactinemic galactorrhea. We managed this side effect initially by dose reduction and further by switching to essitalopram. Physicians should be aware of endocrinologic side effects such as galactorrhea during the serotonin and noradrenaline reuptake inhibitor treatment.

Codeine Precipitating Serotonin Syndrome in a Patient in Therapy with Antidepressant and Triptan

The serotonin syndrome is a serioius medical condition due due to an intensive stimulation of setonin receptors. It is a rare, but severe, consequence of interaction between serotomimetic agents. This is a report of a 70-year-old woman steadily in therapy with venlafaxine and rizatriptan for migraine and major depressive syndrome. She was admitted to neurology unit for decreased light reflex with miotic pupils, global hyperreflexia, tremor, anxiety, ataxia and incoordination. The patient was diagnosed as a probable case of serotonin syndrome due to a pharmacological interaction between venlafaxine and rizatriptan trigged by opioid intake. In this paper, the development of syntomatology, the clinical examination and the possible pharmacokinetics explanation were carefully discussed and analysed.

TeleCondutas: ansiedade / TeleGuides: anxiety

A ansiedade pode ser vista como sintoma psiquiátrico e/ou como reação emocional não patológica associada a diversos contextos de vida. Ela representa um sinal de alarme a determinado estímulo percebido pelo indivíduo como perigoso. Em geral, é composta por uma combinação variável de sintomas físicos, pensamentos catastróficos e alterações de comportamento. A ansiedade pode ser compreendida como mecanismo evolutivo, isto é, uma ferramenta que nos ajuda a detectar o perigo e adotar as medidas necessárias para lidar com ele. No entanto, esse recurso adaptativo muitas vezes encontra-se desregulado, causando sofrimento e prejuízo ao desempenho social e/ou profissional. A ansiedade se torna um transtorno psiquiátrico quando representa emoção desconfortável e inconveniente, surgindo na ausência de um estímulo externo claro ou com magnitude suficiente para justificá-la, e apresenta intensidade, persistência e frequência desproporcionais. Estudos epidemiológicos indicam os transtornos de ansiedade como os mais prevalentes dentre os transtornos psiquiátricos. Na grande maioria dos casos, não há como estabelecer uma causa específica aos transtornos aqui tratados. A interação entre fatores genéticos e ambientais resume a etiologia atualmente proposta e aceita. Esta guia apresenta informação que orienta a conduta para casos de ansiedade no contexto da Atenção Primária à Saúde, incluindo: Diagnóstico, Diagramas diagnósticos, Condições de saúde associadas aos sintomas, Fármacos associados aos sintomas, Abordagem psicoeducativa/psicossocial, Tratamento conforme diagnóstico, Medicamentos e dose, Quando encaminhar.

Análisis de costo-efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de fobia social en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline, fluoxetine and venlafaxine as maintenance therapy for patients with social phobia disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina, y venlafaxina como terapia de mantenimiento en adultos con diagnóstico de trastorno de fobia social en Colombia. Tipo de evaluación económica: Análisis de costo-utilidad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de fobia social. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina, fluoxetina, y venlafaxina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS. Tasa de descuento: No aplica. Estructura del modelo: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. Fuentes de datos de efectividad y seguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: AVAC, Tasa de respuesta al medicamento. Costos incluidos: Costo de los medicamentos, Costo de procedimientos, Costo de los eventos adversos. Fuentes de datos de costos: SISMED. Manual tarifario ISS 2001. Resultados del caso base: Para el caso base, paroxetina, sertralina y venlafaxina son dominados por fluoxetina y escitalopram. El costo por AVAC ganado con escitalopram comparado con fluoxetina se estimó en $30.968.662. Todas las alternativas tienen una efectividad esperada muy similar. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado mostraron que las variables con mayor impacto sobre las estimaciones de costo-utilidad del escitalopram son la probabilidad de respuesta y las ponderaciones de utilidad. Conclusiones y discusión: Escitalopram parece ofrecer una mejor relación entre costos y efectividad respecto a sus comparadores. No obstante, es necesario tener en cuenta que sertralina, paroxetina y fluoxetina pueden llegar a ser costo-efectivas debido a que variaciones en los parámetros de efectividad y utilidad pueden cambiar la decisión. Venlafaxina obtuvo una peor relación de costos y beneficios comparativos. La principal limitación de este estudio se centra en la ausencia de ensayos clínicos de no inferioridad con un horizonte de largo plazo. (AU)

Análisis de impacto presupuestal de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes adultos con trastorno de ansiedad generalizada en Colombia / Budget impact analysis of escitalopram, paroxetine and venlafaxine as maintenance therapy for adult patients with generalized anxiety disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina y venlafaxina, Actuales: sertralina y fluoxetina. Población: Pacientes mayores de 18 años con trastorno de ansiedad generalizada en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos por mg de los medicamentos analizados. Fuente de costos: Los precios de cada tecnologías considerada fueron calculados con la base de datos SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados, igualándose en el año 3. En el escenario 2, además de dicha igualación de participaciones de mercado, se asumen un precio común para las nuevas alternativas, siguiendo las metodologías de inclusión fe grupos terapéuticos definidas\r\npor el Ministerio de Salud y Protección Social. Resultados: Para la inclusión en el POS de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de ansiedad\r\ngeneralizada en Colombia, se requeriría una inversión de $5.874.138.950 en el año 1 y de $5.795.867.954 en el año 3. En el caso en el que los medicamentos del escenario nuevo sean incluidos con un precio común\r\nbasado en las metodologías de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal se reduciría a $664.806.300 en el año 1 y $631.634.228, en el año 3.(AU)

Análisis de impacto presupuestal de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes adultos con trastorno de fobia social en Colombia / Budget impact analysis of escitalopram, paroxetine and venlafaxine as maintenance therapy for adult patients with social phobia disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina y venlafaxina, Actuales: sertralina y fluoxetina. Población:\tPacientes mayores de 18 años con trastorno de fobia social en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercero pagador, que en este caso es el Sistema General de Seguridad Social en Salud (SGSSS) en Colombia. Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos por mg de los medicamentos analizados. Fuente de costos: Los precios de cada tecnologías considerada fueron calculados con la base de datos SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados, igualándose en el año 3. En el escenario 2, además de dicha igualación de participaciones de mercado, se asumen un precio común para las nuevas alternativas, siguiendo las metodologías de inclusión fe grupos terapéuticos definidas\r\npor el Ministerio de Salud y Protección Social. Resultados: Para la inclusión en el POS de escitalopram, paroxetina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de fobia social en\r\nColombia, se requeriría una inversión de $44.181.317.390 en el año 1 y de $34.102.843.305 en el año 3. En el caso en el que los medicamentos del escenario nuevo sean incluidos con un precio común basado en las\r\nmetodologías de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal se reduciría a $5.822.672.775 en el año 1 y $3.330.318.162, en el año 3.(AU)

Análisis de costo-efectividad de escitalopram comparado con paroxetina, sertralina y venlafaxina como terapia de mantenimiento para pacientes con trastorno de ansiedad generalizada en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline and venlafaxine as maintenance therapy for patients with generalized anxiety disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina y venlafaxina como terapia de mantenimiento en adultos con diagnóstico de trastorno de ansiedad generalizada en Colombia. Tipo de evaluación económica: Análisis de costo-utilidad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de ansiedad generalizada. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina y venlafaxina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS. Tasa de descuento: No aplica. Estructura del modelo: Se estructuró un árbol de decisión, teniendo en cuenta modelos publicados en la literatura. Fuentes de datos de efectividad y seguridad: Reporte de efectividad y seguridad elaborado en diciembre de 2014 en el IETS, Ensayos clínicos aleatorizados. Desenlaces y valoración: AVAC, Tasa de respuesta al medicamento, Tasa de recaídas con el medicamento. Costos incluidos: Costo de los medicamentos, Costo de procedimientos, Costo de los eventos adversos. Fuentes de datos de costos: SISMED, Manual tarifario ISS 2001. Resultados del caso base: Para el caso base, escitalopram es la alternativa cost-efectiva con un costo esperado de $39.127.045 respecto a sertralina. La RICE de paroxetina fue superior al umbral de costo-efectividad de 3 veces el PIB per cápita. Venlafaxina fue dominada por todos los demás medicamentos. Se encuentra gran incertidumbre en la decisión y una e fectividad esperada muy similar entre todas las alternativas, por lo que estos resultados deben analizarse con precaución. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado mostraron que las variables con mayor impacto sobre las estimaciones de costo-utilidad del escitalopram son la probabilidad de respuesta, ponderaciones de utilidad, las dosis de los medicamentos y el desenlace utilizado. Conclusiones y discusión: Escitalopram parece ofrecer una mejorrelación entre costos y efectividad respecto a sus comparadores. No obstante, es necesario tener en cuenta que sertralina y paroxetina pueden llegar a ser costo-efectivas bajo escenarios plausibles. Venlafaxina obtuvo una peor relación de costos y beneficios comparativos. La principal limitación de este estudio se centra en la ausencia de ensayos clínicos de no inferioridad con un horizonte de largo plazo.(AU)

Effects of Persisting Emotional Impact from Child Abuse and Norepinephrine Transporter Genetic Variation on Antidepressant Efficacy in Major Depression: A Pilot Study

OBJECTIVE: Previous studies suggest child abuse and serotonergic polymorphism influence depression susceptibility and anti-depressant efficacy. Polymorphisms of the norepinephrine transporter (NET) may also be involved. Research in the area is possibly clouded by under reporting of abuse in researcher trials. METHODS: Adults (n=51) with major depressive disorder has 8 weeks treatment with escitalopram or venlafaxine. Abuse history was obtained, the ongoing emotional impact of which was measured with the 15-item impact of event scale (IES-15). The 17-item Hamilton Depression Rating Scale (HDRS) was applied serially. Two NET polymorphisms (rs2242446 and rs5569) were assayed, blinded to HDRS ratings and abuse history. RESULTS: No subjects reporting abuse with high impact in adulthood (IES-15 > or =26, n=12) remitted; whereas 77% reporting low impact (IES-15 <26; n=26) remitted (p<0.001). Subjects reporting high impact abuse (n=12) had a 50-fold (95% confidence interval=4.85-514.6) greater odds of carrying rs2242446-TT genotype, but the small sample size leaves this finding vulnerable to type I error. CONCLUSION: The level of persisting impact of child abuse appears relevant to antidepressant efficacy, with susceptibility to such possibly being influence by NET rs2242446 polymorphism. Larger studies may be merited to expand on this pilot level finding given potential for biomarker utility.