Eficácia e segurança de Duloxetina comparado a outros antidepressivos disponíveis no SUS para o tratamento de depressão maior: revisão rápida de evidências / Effectiveness and safety of Duloxetine compared to other antidepressant agents available in Brazilian Public Health for treatment of major depression: rapid response review of evidence

Tecnologia: Duloxetina e outros antidepressivos disponíveis no Sistema Único de Saúde (amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona). Indicação: Tratamento do primeiro episódio depressivo no transtorno de depressão maior em adultos. Pergunta: A duloxetina é mais eficaz e tolerável que a amitriptilina, nortriptilina, clomipramina, fluoxetina e bupropiona para o tratamento do primeiro episódio de depressão maior em adultos? Métodos: Revisão rápida de evidências (overview) de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews). Resultados: Foi selecionada 1 revisão sistemática, que atendia aos critérios de inclusão. Conclusão: Os antidepressivos, comparados ao placebo, tinham maior taxa de resposta, taxa de remissão e taxa de descontinuação devido a efeitos colaterais, no tratamento de curto prazo. Duloxetina tinha taxa de resposta similar a amitriptilina, clomipramina, fluoxetina e bupropiona. Duloxetina e amitriptilina tinham maior taxa de remissão que fluoxetina. Comparando-se as taxas de abandono de tratamento devido a efeitos colaterais, clomipramina era menos seguro, amitriptilina, bupropiona e duloxetina eram parecidos entre si, e fluoxetina era o antidepressivo mais seguro

Technology: Duloxetine and other antidepressants available in the Brazilian Public Health System (amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion). Indication: Treatment of the first depressive episode in adult major depressive disorder. Question: Is duloxetine more effective and tolerable than amitriptyline, nortriptyline, clomipramine, fluoxetine and bupropion for the treatment of first episode of major depression in adults? Methods: Rapid response review of evidence (overview) from systematic reviews, with a bibliographic search in the PUBMED database, using a structured strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (Methodological Quality Assessment of Systematic Reviews). Results: One systematic review was selected, which met the inclusion criteria. Conclusion: In short-term treatment, antidepressants, compared to placebo, had a higher rate of response, rate of remission and rate drop-out due to side effects. Duloxetine had a similar response rate to amitriptyline, clomipramine, fluoxetine and bupropion. Duloxetine and amitriptyline had higher remission rates than fluoxetine. Comparing rates of dropout due to side effects, clomipramine had the worst rates, amitriptyline, bupropion, and duloxetine were similar to each other, and fluoxetine had the better rates

The effect of antidepressant treatment on the HPA axis, changes in depression score and serum levels of TNF-α in depressed infertile women

Abstract Objectives This study aimed to explore the effect of antidepressant treatment on the HPA axis, changes in depression score, and serum levels of TNF-α in depressed infertile women. Methods In this randomized controlled trial research, 60 infertile women who had undergone in vitro fertilization (IVF) treatment with depression scores between 16-47 were divided into two groups. The intervention group with fluoxetine capsule was under treatment for two months before the embryo transfer, while the control group was given placebo. Depression score, serum levels of tumor necrosis factor alpha (TNF-α) as well as cortisol hormone levels were measured and recorded both before and after the intervention. The data were analyzed using SPSS version 21 software. Results We analyzed the data related to 55 subjects who had undergone embryo transfer. 7 subjects in the intervention group and 3 in the control group got pregnant. We observed a significant decrease in the depression score (p < 0/001) and serum levels of cortisol (p = 0/001) in the intervention group. There was a significant increase in the serum levels of TNF-α in the intervention group (p < 0/001). There was a significant difference between the two groups in the number of pregnancies (p = 0.04). However, there was no statistical difference between them with regard to the number of harvested oocytes (p = 0.174). Discussion Decrease in depression score and cortisol level, and an increase in the levels of TNF-α in the intervention group caused any changes in the number of oocytes in comparison with the control group. However, the number of pregnancies was larger in the intervention group.

Treatment data from the Brazilian fibromyalgia registry (EpiFibro)

Abstract Background: EpiFibro (Brazilian Epidemiological Study of Fibromyalgia) was created to study patients with fibromyalgia (FM). Patients were included since 2011 according to the classification criteria for FM of the American College of Rheumatology of 1990 (ACR1990). Objective: To analyze the therapeutic measures prescribed by Brazilian physicians. Materials and methods: Cross-sectional study of a multicenter cohort. The therapeutic measures were described using descriptive statistics. Results: We analyzed 456 patients who had complete data in the registry. The mean age was 54.0 ± 11.9 years; 448 were women (98.2%). Almost all patients (98.4%) used medications, 62.7% received health education, and less than half reported practicing physical exercise; these modalities were often used in combination. Most patients who practiced exercises practiced aerobic exercise only, and a significant portion of patients combined it with flexibility exercises. The most commonly used medication was amitriptyline, followed by cyclobenzaprine, and a minority used medication specifically approved for FM, such as duloxetine and pregabalin, either alone or in combination. Combinations of two or three medications were observed, with the combination of fluoxetine and amitriptyline being the most frequent (18.8%). Conclusion: In this evaluation of the care of patients with FM in Brazil, it was found that the majority of patients are treated with a combination of pharmacological measures. Non-pharmacological methods are underused, with aerobic exercise being the most commonly practiced exercise type. The most commonly prescribed single drug was amitriptyline, and the most commonly prescribed combination was fluoxetine and amitriptyline. Drugs specifically approved for FM are seldom prescribed.(AU)

Management of the pseudobulbar affect (PBA) in Kabuki syndrome combined dextromethorphan-fluoxetine treatment as an alternative to dextromethorphan/quinidine

A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global Impression-Improvement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) ­ especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It's could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary. (AU)

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)

Which of available selective serotonin reuptake inhibitors (SSRIs) is more effective in treatment of premature ejaculation? A randomized clinical trial

ABSTRACT Purpose: To compare the efficacy and safety of available selective serotonin reuptake inhibitors (SSRIs) in order to find the most effective drug with the least number of side effects in treatment of premature ejaculation (PE). Materials and Methods: This study was a randomized clinical trial. Four hundred and eighty patients with PE in the 4 groups referred to Imam Reza hospital Tehran, Iran from July 2018 to February 2019 were enrolled in the study. The patients received sertraline 50mg, fluoxetine 20mg, paroxetine 20mg and citalopram 20mg, every 12 hours daily. The intravaginal ejaculatory latency time (IELT) before treatment, fourth and eighth weeks after treatment was recorded by the patient's wife with a stopwatch. Results: Mean IELT before, 4 and 8 weeks after treatment in four groups were: sertraline 69.4±54.3, 353.5±190.4, 376.3±143.5; fluoxetine 75.5±64.3, 255.4±168.2, 314.8±190.4; paroxetine 71.5±69.1, 320.7±198.3, 379.9±154.3; citalopram 90.39±79.3, 279.9±192.1, 282.5±171.1 seconds, respectively. The ejaculation time significantly increased in all groups (p <0.05), but there was no significant difference between the groups (P=0.75). Also, there was no significant difference in drugs side effects between groups (p >0.05). The most common side effects were drowsiness and dyspepsia, which were not severe enough to cause discontinuation of the drug. Conclusions: All available SSRIs were effective and usually had no serious complications. In patients who did not respond to any of these drugs, other SSRI drugs could be used as a salvage therapy.

Trichotillomania: a case report with clinical and dermatoscopic differential diagnosis with alopecia areata

ABSTRACT Trichotillomania is a psychodermatologic disorder characterized by uncontrollable urge to pull one's own hair. Differential diagnoses include the most common forms of alopecia such as alopecia areata. It is usually associated with depression and obsessive-compulsive disorder. Trichotillomania treatment standardization is a gap in the medical literature. Recent studies demonstrated the efficacy of N-acetylcysteine (a glutamate modulator) for the treatment of the disease. We report the clinical case of a 12-year-old female patient who received the initial diagnosis of alopecia areata, but presented with clinical and dermoscopic features of trichotillomania. She was treated with the combination of psychotropic drugs and N-acetylcysteine with good clinical response. Due to the chronic and recurring nature of trichotillomania, more studies need to be conducted for the establishment of a formal treatment algorithm.

Análisis de costo-efectividad del escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento para pacientes con trastorno de pánico en Colombia / Cost-effectiveness analysis of escitalopram compared to paroxetine, sertraline, fluoxetine, imipramine and fluvoxamine as maintenance therapy for patients with panic disorder in Colombia

Problema de investigación: Describir los costos y la efectividad de escitalopram comparado con paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina como terapia de mantenimiento en adultos con diagnóstico de trastorno de pánico en Colombia. Tipo de evaluación económica: Análisis de costo-efectividad. Población objetivo: Adultos colombianos con diagnóstico de trastorno de pánico. Intervención y comparadores: Intervención: escitalopram, Comparadores: paroxetina, sertralina, fluoxetina, imipramina y fluvoxamina. Horizonte temporal: 32 semanas. Perspectiva: SGSSS de Colombia. 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, Ensayo s clínicos a leatorizados. Desenlaces y valoración: Ausencia de crisis de pánico, Semanas libres de crisis de pánico. 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, fluvoxamina y fluoxetina e imipramina fueron tecnologías dominadas por sertralina y paroxetina. El costo adicional por crisis de pánico evitada en tratamiento con paroxetina comparado con trasertralina se estimó en $4.814.953. Análisis de sensibilidad: Los análisis de sensibilidad y el diagrama de tornado muestran a la probabilidad de lograr ausencia de crisis de pánico y la probabilidad de recaída, como a las variables con mayor impacto sobre las estimaciones de la razón de costo-efectividad. Conclusiones y discusión: De acuerdo con los hallazgos aquí presentados, paroxetina, ofrece mayor razón de costo-efectividad, respecto a sus comparadores. No obstante, es \r\nnecesario tener en cuenta que cualquiera de las alternativas aquí estudiadas, puede ser costo-efectiva, debido a que las pequeñas variaciones en la probabilidad de ausencia de crisis de pánico pueden cambiar el resultado. La principal limitación de este estudio es la ausencia de información roveniente de estudios de investigación clínica, que muestre el desempeño comparativo entre las tecnologías, así como el seguimiento de los participantes en los estudios, en escenarios de más largo plazo que los existentes al momento de elaborar este documento.(AU)

Análisis de impacto presupuestal de escitalopram, paroxetina, sertralina, fluoxetina, fluvoxamina y clomipramina como terapia de mantenimiento para pacientes adultos con trastorno obsesivo compulsivo en Colombia / Budget impact analysis of escitalopram, paroxetine, sertraline, fluoxetine, fluvoxamine and clomipramine as maintenance therapy for adult patients with obsessive-compulsive disorder in Colombia

Tecnologías evaluadas: Nuevas: escitalopram, paroxetina, fluvoxamina y clomipramina\r\nActuales: sertralina y fluoxetina. Población: Pacientes mayores\tde\t18 años\tcon trastorno\tobsesivo\r\ncompulsivo en Colombia. Perspectiva: La perspectiva del presente AIP corresponde al tercer pagador,\r\nque 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 es de 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 incluídos: Costo por mg de los medicamentos. Fuente de costos: SISMED. Escenarios: En el escenario 1 se considera una igualación progresiva de las participaciones de mercado de todos los medicamentos analizados hasta llegar al año 3. En el escenario 2, además de una participación\tde\tmercado\tigual para\ttodos los medicamentos, se asume un precio común para las nuevas alternativas con base en la metodología de inclusión de grupos terapéuticos definida por el Ministerio de Salud y Protección\r\nSocia. Resultados: Para la inclusión en el POS de escitalopram, paroxetina, fluvoxamina y Clomipramina como terapia de mantenimiento para pacientes con diagnóstico de trastorno obsesivo ompulsivo en Colombia, se requeriría una inversión de $99.508.967.049 en el año 1 y de $136.213.036.626 en el año 3. En el caso que los medicamentos del escenario nuevo sean incluidos con un precio igual basado en las metodología de grupos terapéuticos del Ministerio de Salud y protección Social, el impacto presupuestal\r\nse reduciría a $13.170.025.624 en el año 1 y $19.887.249.147, en el año 3.(AU)

Possible solutions to the shortcomings of the Yale-Brown Obsessive-Compulsive Scale / Possíveis soluções para as deficiências da escala de Yale-Brown para avaliação do transtorno obsessivo-compulsivo

OBJECTIVE: The Yale-Brown Obsessive-Compulsive Scale is the most frequently used instrument to measure obsessive-compulsive symptom severity. We describe its shortcomings and propose new methods of evaluating current severity and treatment response. METHOD: The Yale-Brown Obsessive-Compulsive Scale total and subscale scores were pooled from one cross-sectional study database containing information on 1,000 obsessive-compulsive disorder patients from seven specialized mental health care centers. Additional longitudinal data were pooled for 155 patients who participated in a 12-week trial that evaluated the effectiveness of fluoxetine vs. cognitive-behavior therapy as first-line treatment options. All patients were followed by a clinician who provided a clinical opinion of improvement. Neither patients nor clinicians were aware of the classifications proposed in this study. New methods for using the severity scores were compared with the clinical opinion of improvement. RESULTS: In the Yale-Brown Obsessive-compulsive scale, the summing-up of subscale scores to compose a total score does not accurately reflect clinical severity. In addition, the reduction of scores with treatment does not usually reach score zero in either subscale. To overcome such problems, we suggest (a) use of the maximum score of any of the subscales; (b) use of a minimum score of 4 in each subscale or 5 for the maximum in any subscale as the goal after treatment. This method performed better than traditional ones regarding sensitivity and specificity against the gold standard represented by the clinical opinion of improvement. CONCLUSION: The new proposed response criteria are coherent with the clinical opinion of improvement and perform better than the traditional methodology.

RESUMO OBJETIVO: A escala de Yale-Brown para avaliação do transtorno obsessivo-compulsivo é o instrumento mais utilizado para medir a gravidade desse transtorno. Descrevemos as deficiências dessa escala e propomos novos métodos de cálculo dos escores para avaliação de gravidade e resposta ao tratamento. MÉTODO: Os escores totais e subtotais da escala de Yale-Brown foram recuperados de um banco de dados de um estudo transversal com informações sobre 1.000 pacientes com transtorno obsessivo-compulsivos atendidos em sete centros especializados em saúde mental. Foram acrescentados os dados longitudinais de 155 pacientes participantes de um ensaio clínico de 12 semanas que avaliou a eficácia da fluoxetina ou da terapia cognitivo-comportamental como opções de tratamento de primeira linha. Todos os pacientes foram acompanhados por um médico que forneceu um parecer clínico de melhora. Nem os pacientes nem os médicos estavam conscientes das classificações propostas neste estudo. Novos métodos para avaliar os escores de gravidade foram comparados com o parecer clínico de melhora. RESULTADOS: Na escala obsessivo-compulsiva Yale-Brown, a soma de sub-escalas para compor a pontuação total não reflete com precisão a gravidade clínica. Além disso, a redução da pontuação com o tratamento, normalmente, não atinge o valor zero em qualquer das sub-escalas. Para superar esses problemas, sugerimos (a) o uso da pontuação máxima de qualquer das sub-escalas antes do tratamento; (b) o uso de um score mínimo de 4 em cada sub-escala ou um escore mínimo de 5 como o máximo de qualquer das sub-escalas como a meta para o pós-tratamento. Os novos métodos propostos tiveram melhor desempenho do que os tradicionais quanto a sensibilidade e especificidade contra o padrão ouro representado pelo parecer clínico de melhora. CONCLUSÃO: Os novos critérios propostos são coerentes com o parecer clínico de melhora e desempenham melhor do que a metodologia tradicional.

Utilización de antidepresivos en pacientes ambulatorios del Hospital Policial / Use of antidepressants in outpatient Hospital Policial

El presente es un estudio de consumo de antidepresivos (ad) en el Hospital Policial de tercer nivel de atención. El objetivo del trabajo es determinar el consumo de ad en el período enero 2010-diciembre 2014. Se trata de un estudio observacional y retrospectivo del consumo de ad. Se utilizó el método dosis diaria definida (ddd) por 1000 habitantes por día (dhd). El estudio incluyó los consumos de ad de pacientes ambulatorios en el período enero 2010-diciembre 2014. De los resultados se destaca que el valor total de dhd presentó un aumento del 8 %. Los ad más consumidos en el período estudiado fueron sertralina y fluoxetina. Se observó un incremento lineal significativo en el consumo de venlafaxina, citalopram, escitalopram y fluvoxamina. El consumo de aden la población pediátrica disminuyó un 66 %. La medición del consumo de ad para el período enero 2010-diciembre 2014 proporciona un diagnóstico inicial de situación en el Hospital Policial.

Treatment effect on temperament and character in panic disorder: a prospective randomized double-blind study / Efeito de tratamento sobre temperamento e caráter no transtorno de pânico: estudo randomizado prospectivo duplo-cego

OBJECTIVE: The present study aims to analyze the effect of pharmacological treatment for panic disorder on temperament and character dimensions and to compare the effect of imipramine and fluoxetine on this outcome. METHOD: Temperament and character dimensions were evaluated in panic disorder patients before and after six months of pharmacological treatment with imipramine and fluoxetine, using the Temperament and Character Inventory-Revised. Patients were randomized between groups and both (patient and investigators) were blinded to the intervention drug. Furthermore, 34 non-panic controls answered the revised Temperament and Character Inventory through an Internet survey. RESULTS: Panic disorder patients showed higher scores for Harm Avoidance and lower scores for Persistence, Self-Directedness, and Cooperativeness than controls at baseline, but only the low Persistence value remained different from controls after treatment. Responder patients presented significant reduction in Harm Avoidance scores and a significant increase in Self-Directedness scores, whereas non-responders showed a significant increase of Harm Avoidance levels. Fluoxetine and Imipramine showed similar effects on the revised Temperament and Character Inventory dimensions. CONCLUSION: High Harm Avoidance and low Self-Directedness, Persistence, and Cooperativeness are associated with panic disorder. Treatment of acute panic disorder symptoms lead to the reduction of Harm Avoidance and to an increase in Self-Directedness scores. However, there was no difference between treatment with fluoxetine and imipramine for the effect on the revised Temperament and Character Inventory dimensions.

OBJETIVO: O presente estudo tem como objetivo analisar o efeito do tratamento farmacológico do transtorno do pânico nas dimensões de temperamento e caráter, comparando os efeitos das medicações imipramina e fluoxetina neste desfecho. METODOLOGIA: As dimensões de temperamento e caráter foram avaliadas em pacientes com transtorno do pânico antes e depois de seis meses de tratamento com imipramina ou fluoxetina, utilizando-se o "Temperament and Character Inventory- Revised" (TCI-R). O estudo foi randomizado e duplo-cego. Além disso, 34 controles sem transtorno do pânico responderam ao TCI-R via internet. RESULTADOS: Pacientes com transtorno do pânico apresentaram maior pontuação para "Harm Avoidance" e menor pontuação para "Persistence", "Self-Directedness" e "Cooperativeness" que os controles antes do tratamento, mas apenas "Persistence" manteve a diferença após o tratamento. Pacientes respondedores apresentaram redução significativa da pontuação para "Harm Avoidance" e aumento significativo para "Self-Directedness" após o tratamento, enquanto os não-respondedores mostraram aumento significativo na pontuação para "Harm Avoidance". A fluoxetina e a imipramina apresentaram efeitos semelhantes nas dimensões do TCI-R. CONCLUSÃO: Alta pontuação para "Harm Avoidance" e baixa para "Persistence", "Self-Directness" e "Cooperativeness" estão associados ao transtorno do pânico. O tratamento sintomático do transtorno do pânico leva a redução da pontuação para "Harm Avoidance" e aumento de pontuação para "Self-Directedness". No entanto, não há diferença entre os efeitos da imipramina e da fluoxetina nestas dimensões do TCI-R.

Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

A Case of Superior Mesenteric Artery Syndrome Caused by Anorexia Nervosa / 대한소화기학회지

Superior mesenteric artery (SMA) syndrome is a rare disorder, characterized by compression of the third segment of the duodenum by the mesenteric artery at the level of the SMA, resulting in duodenal dilatation. Precipitating factors of the SMA syndrome include prolonged bed rest, weight loss, abdominal surgery, and increased lordosis of the spine. We report a case of SMA syndrome caused by anorexia nervosa in a 15-year-old adolescent girl. CT and an upper gastrointestinal contrast series revealed partial obstruction of the third portion of duodenum and decreased aortomesenteric distance. The patient's symptoms were successfully treated with total parental nutrition and psychiatric treatment including supportive, cognitive behavioral therapy and antidepressant medication. This case shows that SMA syndrome is an unusual gastrointestinal complication that may occur in patients with anorexia nervosa.

Respuesta a fluoxetina y polimorfismos del transportador de serotonina en trastorno límite de personalidad / Fluoxetine response and serotonin transporter polymorphism in borderline personality disorders

Introduction: Impulsiveness and aggressiveness are characteristics of borderline personality disorders. Aggressive and impulsive behaviors are associated to a serotoninergic system dysfunction and are treated with selective serotonin reuptake inhibitors (SSRJs). The short (S) allele of the serotonin transporter promoter (5-HTTPR) gene is associated to a worse response to SSRI in major depression. The objective of this work is to study the anti-impulsive effect of fluoxetine and his relation with short and long alleles of 5-HTTPR gene in borderline personality disordered patients. Method: 59 patients with DSM-IV borderline personality disorder were treated with fluoxetine for 12 weeks. Impulsivity was evaluated with the Overt Aggression Scale Modified (OAS-M). Polymorphisms L and S of the 5-HTTPR gene were determined. Results: S carriers (LS and SS) had a significantly minor response on OAS-M and Aggression subscale than LL carriers. Conclusions: S allele of the 5-HTTPR gene predicts poor response to anti-impulsive effect of fluoxetine in borderline personality disorder. It is likely that multiple genes contribute to a SSRI response.

Introducción: Los trastornos límite de personalidad se caracterizan por una elevada impulsividad y agresividad. Las conductas agresivas e impulsivas se han asociado a disfunciones del sistema serotoninérgico y responden a los inhibidores de la recaptura de serotonina (ISRS). En depresión mayor el alelo corto (S) del promotor del gene del transportador de serotonina se asocia a pobre respuesta a los ISRS. El objetivo de este trabajo es estudiar el efecto anti-impulsivo de serotonina y su relación con los alelos LyS en pacientes con trastorno límite de personalidad. Método: 59 pacientes con trastorno límite de personalidad fueron tratados por 12 semanas confluoxetina. Se evaluó la impulsividad mediante la Overt Aggression Scale Modified (OAS-M)y se determinó los polimorfismos LyS. Resultados: Los portadores de S (LS y SS) presentaron una menor reducción en la OAS-M total y en la subescala de agresividad que los homocigotos LL. Conclusiones: En trastorno límite de personalidad el alelo S del promotor del gene del transportador de serotonina predice pobre respuesta anti-impulsiva de la fluoxetina. Probablemente múltiples genes participen en la respuesta a los ISRS.

The drug-naïve OCD patients imaging genetics, cognitive and treatment response study: methods and sample description / Estudo de genética, imagem, cognição e resposta a tratamento em pacientes com TOC virgens de tratamento: métodos e descrição da amostra

OBJECTIVE: To describe a protocol that was based on an integrative neurobiological model of scientific investigation to better understand the pathophysiology of obsessive-compulsive disorder and to present the clinical and demographic characteristics of the sample. METHOD: A standardized research protocol that combines different methods of investigation (genetics, neuropsychology, morphometric magnetic resonance imaging and molecular neuroimaging of the dopamine transporter) obtained before and after treatment of drug-naïve adult obsessive-compulsive disorder patients submitted to a sequentially allocated 12-week clinical trial with a selective serotonin reuptake inhibitor (fluoxetine) and group cognitive-behavioral therapy. RESULTS: Fifty-two treatment-naïve obsessive-compulsive disorder patients entered the clinical trial (27 received fluoxetine and 25 received group cognitive-behavioral therapy). At baseline, 47 blood samples for genetic studies, 50 neuropsychological evaluations, 50 morphometrical magnetic resonance images and 48 TRODAT-1 single-photon emission computed tomography (SPECT) exams were obtained. After 12 weeks, 38 patients completed the protocol (fluoxetine = 20 and GCBT = 18). Thirty-eight neuropsychological evaluations, 31 morphometrical magnetic resonance images and 34 TRODAT-1 SPECT exams were obtained post-treatment. Forty-one healthy controls matched for age, gender, socioeconomic status, level of education and laterality were submitted to the same research procedures at baseline. CONCLUSION: The comprehensive treatment response protocol applied in this project allowing integration on genetic, neuropsychological, morphometrical and molecular imaging of the dopamine transporter data in drug-naïve patients has the potential to generate important original information on the neurobiology of obsessive-compulsive disorder, and at the same time be clinically meaningful.

OBJETIVO: Descrever um protocolo integrativo de investigação neurobiológica para melhor compreender as bases patofisiológicas do transtorno obsessivo-compulsivo e apresentar as características clínicas e demográficas da amostra. MÉTODO: Protocolo padronizado que combina diferentes modalidades de investigação (genética, neuropsicologia, ressonância magnética cerebral e imagem molecular do transportador de dopamina) obtidas antes e depois do tratamento em pacientes com transtorno obsessivo-compulsivo nunca expostos à medicação submetidos a um ensaio clínico comparando um inibidor seletivo da recaptação de serotonina (fluoxetina) e terapia cognitivo-comportamental em grupo. RESULTADOS: Cinquenta e dois pacientes com transtorno obsessivo-compulsivo entraram no ensaio clínico (27 no grupo fluoxetina e 25 no grupo de terapia). No início, foram realizadas 47 coletas de sangue para genética, 50 avaliações neuropsicológicas, 50 ressonâncias magnéticas cerebrais e 48 exames de tomografia computadorizada por emissão de fóton único (SPECT) com TRODAT-1. Depois de 12 semanas, 38 pacientes terminaram o protocolo (20 no grupo de fluoxetina e 18 no grupo de terapia). Trinta e oito reavaliações neuropsicológicas, 31 ressonâncias magnéticas de crânio e 34 exames de SPECT foram obtidos após o tratamento. Quarenta e um controles pareados foram submetidos ao mesmo protocolo inicial. CONCLUSÃO: Os dados genéticos, neuropsicológicos, volumétricos e moleculares do transportador de dopamina aliados à resposta a tratamento podem tanto gerar informações importantes a respeito da neurobiologia do transtorno obsessivo-compulsivo quanto ter uma aplicação clínica.

Morphological aspects of the embryonic development of the TMJ in rats (Rattus norvegicus albinus) treated with fluoxetine / Aspectos morfológicos del desarrollo embrionario de la ATM en ratas (Rattus norvegicus albinus) tratadas con fluoxetina

The TMJ has been to the Dental community a key point in the search of knowledge, being it part of the temporomandibular joint complex and of the estomatognathic system which are in charge of the mastication, speech, swallowing, as well as participation in breathing and taste perception. For the majority of the women in serious state of depression, which do not respond psychotherapeutic treatment, pharmacological treatment it's applied. The antidepressants serotonin selective reuptake inhibitors (SSRIs) are the most recommended in these cases. The teratogenic effect of the SSRIs is considered controversial, studies done with women who used these drugs during the pregnancy showed that the respiratory and central nervous systems are the most affected, was also recorded a deficit of body growth and the decrease of the encephalon and skull measures. In the present study, our goal was to assess whether the administration of Fluoxetine during the pregnancy modified the embryology and morphology of the TMJ of rats. For that, 16 Wistar female rats from the Nutrition Department of the UFPE vivarium were selected; 8 for the control group, which received daily 0.9 percent of saline in subcutaneous dose of 10ml/g, with schedules previously established after daily weighing and 8 for the experimental one that were treated with fluoxetine hydrochloride with the dose of 10mg/Kg in a volume 10ml/g of weight, were injected subcutaneously with the same standards established for the control group. It was observed, with this dose that the embryological development of the TMJ, especially of the mandibular condyle, does not present any difference between the degree of maturation of the tissue that forms the TMJ, especially of the condyle between the treated and control groups.

La ATM ha sido para la comunidad odontológica un punto clave en la búsqueda del conocimiento, dado que forma parte del complejo articular temporomandibular y del sistema estomatognático, los cuales se encargan de la masticación, fonación y deglución, así como la participación en la respiración y de la percepción gustativa. Para la mayoría de las mujeres con cuadros graves de depresión, que no responden al tratamiento psicoterapéutico, el tratamiento farmacológico es aplicado. Los antidepresivos del grupo de los Inhibidores Selectivos de Recaptación de Serotonina (ISRSs) son los más comúnmente recomendados en estos casos. El efecto teratogénico de los ISRSs es considerado controversial. Estudios realizados en mujeres que utilizaron estas drogas durante la gestación mostraron que los sistemas respiratorios y nervioso central son los más afectados, también fue constatado un déficit de crecimiento corporal, encefálico y disminución de las medidas craneales. En el presente estudio, nuestro objetivo fue evaluar si la administración de fluoxetina durante la gestación modifica la embriología y la morfología de la ATM de ratas de laboratorio. Para este fin, 16 ratas Wistar del bioterio de nutrición de la UFPE fueron seleccionadas: 8 para el grupo de control, las cuales recibieron diariamente solución fisiológica a 0,9 por ciento en aplicaciones subcutáneas en la dosis de 10ml/g, en horarios previamente establecidos después de pesaje diario y 8 para el experimental, las que fueron tratadas con clorhidrato de fluoxetina en la dosis de 10mg/kg, en un volumen de 10ml/g, inyectados por vía subcutánea en los mismos estándares establecidos para el grupo de control. Se observó, que con esta dosis el desarrollo embriológico de la ATM, especialmente del cóndilo mandibular, no presentó ninguna diferencia entre el grado de maduración de los tejidos que forman la ATM, especialmente del cóndilo, entre los grupos tratado y grupo control.

Pharmacoeconomics of antidepressants in moderate-to-severe depressive disorder in Colombia / Farmacoeconomía de antidepresivos en trastornos de depresión moderada e intensa en Colombia

OBJECTIVE: To compare three antidepressant drugs from different classes used in treating moderate-to-severe major depressive disorder (MDD) in Colombian adults. METHODS: Based on expert input, a decision-tree model was adapted for Colombia to analyze data over 6 months from the government-payer perspective. The cost-effectiveness of amitriptyline, fluoxetine, and venlafaxine was determined. The clinical outcome was remission of depression (a score <7 on the Hamilton Depression [HAM-D] scale or <12 on the Montgomery-Åsberg Depression Rating Scale [MADRS]) after 8 weeks of treatment. Clinical data were obtained from the literature and costs from standard Colombian price lists. One-way and multivariate sensitivity analyses tested model robustness. RESULTS: Costs per patient (in 2007 US$) for treatment were: venlafaxine, $1 618; fluoxetine, $1 207; and amitriptyline, $1 068. Overall remission rates were 73.1 percent, 64.1 percent, and 71.3 percent, respectively. Amitriptyline dominated fluoxetine (i.e., it had lower costs and higher outcomes). The incremental cost-effectiveness ratio (ICER) of venlafaxine over amitriptyline was US$ 31 595. The acquisition price of venlafaxine was the model's cost driver, comprising 53.4 percent of the total cost/patient treated, compared with 18.5 percent and 24.8 percent for fluoxetine and amitriptyline, respectively. For the others, hospitalization comprised the major cost (72.1 percent and 65.2 percent, respectively). Probabilistic (Monte Carlo) sensitivity analysis confirmed the original findings of the pharmacoeconomic model. CONCLUSIONS: Amitriptyline is cost-effective in comparison to fluoxetine and venlafaxine in Colombia. However, the cost of venlafaxine was estimated for the brand-name product, as generics were not currently available. These cost-effectiveness results can be substantially affected by the presence of generics or drug cost regulations.

OBJETIVO: Comparar tres medicamentos antidepresivos de diferentes clases empleados para tratar trastornos depresivos mayores moderados e intensos en adultos colombianos. MÉTODOS: A partir de los aportes de expertos se adaptó un modelo de árbol de decisión para Colombia a fin de analizar los datos de seis meses desde la perspectiva del gobierno como pagador de los servicios. Se determinó la relación costo-efectividad de la amitriptilina, la fluoxetina y la venlafaxina. El desenlace clínico fue la remisión de la depresión (una puntuación <7 en la escala de depresión de Hamilton o <12 en la escala de valoración de la depresión de Montgomery-Åsberg) después de 8 semanas de tratamiento. Los datos clínicos se obtuvieron de la literatura especializada y los costos, de las listas habituales de precios de Colombia. Se realizaron análisis de sensibilidad simples y multifactoriales para probar la robustez de los modelos. RESULTADOS: Los costos del tratamiento por paciente (en dólares estadounidenses de 2007) fueron: US$ 1 618 para la venlafaxina, US$ 1 207 para la fluoxetina y US$ 1 068 para la amitriptilina. Las tasas de remisión general fueron 73,1 por ciento, 64,1 por ciento y 71,3 por ciento, respectivamente. La amitriptilina tuvo un menor costo y una mayor remisión que la fluoxetina. La razón de rentabilidad incremental de la venlafaxina sobre la amitriptilina fue de US$ 31 595. El inductor de costos (cost driver) del modelo fue el valor de adquisición de la venlafaxina, que representó 53,4 por ciento del total del costo por paciente tratado, en comparación con la fluoxetina (18,5 por ciento) y la amitriptilina (24,8 por ciento). En los otros casos, la hospitalización representó el mayor costo (72,1 por ciento y 65,2 por ciento, respectivamente). El análisis de sensibilidad probabilístico (Monte Carlo) confirmó los resultados preliminares del modelo farmacoeconómico. CONCLUSIONES: En Colombia, la amitriptilina es más efectiva en función del...