While a comorbid relationship between substance abuse and depression in Caucasian adults has been widely documented, comorbid substance abuse and depression in minorities remains unexplored, leaving a gap in knowledge concerning the treatment of these comorbid disorders in the fastest growing population in the United States. Cognitive behavior theory posits that specific stressors increase the likelihood of substance abuse. These factors may include structural discrimination experienced by minorities. This quantitative, pretest-posttest archival study examined the effects of a substance abuse treatment program in reducing comorbid depressive symptoms among 317 participants from 3 minority subgroups and a comparison nonminority group enrolled in a court-mandated residential program in Texas. Depression scores were assessed at intake and 30 days later by the Client Evaluation of Self and Treatment-Psychological Functioning. Using gender and age as covariates, a 2 x 2 and a 2 x 3 mixed ANOVA design evaluated changes in depression scores among different racial groups. All participants who completed treatment experienced a significant decline in symptoms associated with depression. By adding to the existing literature regarding the successful treatment of those who participate in a CBT-oriented therapy, this study informs programs seeking successful strategies in helping minorities to enter and complete treatment, which lends itself to positive social change. Further, the efficacy of CBT-oriented therapies across all groups, regardless of race or ethnic identity, provides a unique opportunity for counselors and doctors to develop successful long-term strategies for patients struggling with comorbid substance abuse and depression.

No description available.

Low cholesterol concentrations and cholesterol-lowering therapies have been suggested to be associated with increased suicidality. This article examined the association of cholesterol, triglycerides, and body-mass index (BMI) with suicidal ideation and suicide attempts. Findings are based on a nationally representative community sample of n = 4,181 subjects (18–65 years) examined with a standardized diagnostic interview (CIDI) for (DSM-IV) mental disorders. Controlling for age and gender the study revealed a moderate positive association between cholesterol, triglycerides, BMI, and suicide attempts in subjects with depressive symptoms during the past 12 months (n = 1,205). The results of this study are compatible with two recent epidemiological cohort studies showing a positive association between cholesterol and completed suicide.

Low cholesterol concentrations and cholesterol-lowering therapies have been suggested to be associated with increased suicidality. This article examined the association of cholesterol, triglycerides, and body-mass index (BMI) with suicidal ideation and suicide attempts. Findings are based on a nationally representative community sample of n = 4,181 subjects (18–65 years) examined with a standardized diagnostic interview (CIDI) for (DSM-IV) mental disorders. Controlling for age and gender the study revealed a moderate positive association between cholesterol, triglycerides, BMI, and suicide attempts in subjects with depressive symptoms during the past 12 months (n = 1,205). The results of this study are compatible with two recent epidemiological cohort studies showing a positive association between cholesterol and completed suicide.

Schwermut, Einsamkeit, Desinteresse: 2-7% der Weltbevölkerung werden von diesen Gefühlen bestimmt, sie sind an einer Depression erkrankt. In Deutschland leiden aktuell bis zu 4 Mio. Menschen an einer Depression. Zwei Drittel diese Kollektivs befinden sich in hausärztlicher Behandlung, aber nur etwa die Hälfte von diesen Patienten wird korrekt diagnostiziert und behandelt. Die Gründe hierfür sind auf der einen Seite die schwierige Diagnosefindung, auf der anderen die bisher nicht vollständig geklärte Ätiologie und die komplexen Wirkmechanismen der medikamentösen antidepressiven Therapieoptionen. Die Entstehung einer depressiven Episode ist multifaktoriell bedingt, wobei insbesondere genetischen Faktoren in der Pathogenese depressiver Erkrankungen eine wichtige Rolle zugeordnet wird. Neurobiologische Untersuchungen der molekularen und biochemischen Hintergründe von depressiven Episoden befassen sich zurzeit insbesondere mit drei Hypothesen: Diese sind die Neurotransmitter-Dysbalance-Hypothese (Monoaminhypothese), die Stressachsen-Hypothese (Hypothalamus-Hypophysen-Achse) und die Neurotrophin-Hypothese. Die Stressachsen-Hypothese befasst sich in diesem Zusammenhang mit der Aktivität des Hypothalamus-Hypophysen-Systems, die bei depressiv erkrankten Patienten dysreguliert ist und mit einer erhöhten Kortisolsekretion einhergeht. Die Monoaminhypothese der Depression postuliert eine Dysfunktion serotonerger, noradrenerger und dopaminerger Systeme. Die Neurotrophinhypothese bezieht sich auf das Second Messenger-System des durch Antidepressiva aktivierten cyclischen Adenosin-Monophosphat (cAMP) Signalwegs. Cyclisches Adenosin-Monophosphat aktiviert die cAMP-abhängige Proteinkinase (PKA), die wiederum den Transkriptionsfaktor cAMP response element binding protein (CREB) phosphoryliert und ihn somit stimuliert. Aktiviertes CREB verstärkt die Transkription zahlreicher Zielgene, inklusive die des brain-derived neurotrophic factor (BDNF), welcher unter anderem als Regulator von Neurotransmittern dient und Überleben, Differenzierung und Plastizität von Neuronen beeinflusst. Astrozyten gehören zur Gruppe der Makrogliazellen im zentralen Nervensystem (ZNS) und sind die größte Population der Gliazellen. Sie sind für die Kaliumhomöostase und ebenso für die Regulation der synaptischen Transmission und der neurovaskulären Koppelung zuständig. Des Weiteren scheinen Astrozyten eine wichtige Rolle für die Bildung glialer Narben, die Induktion der Blut-Hirn-Schranke und auch für das neuronale Überleben zu spielen. Bei der Analyse der Wirkmechanismen medikamentöser antidepressiver Therapien ist in der letzten Zeit die Rolle der Astrozyten in den Vordergrund gerückt, um deren Beitrag zu antidepressiven Therapien zu untersuchen. Das Ziel der vorliegenden Arbeit war zu untersuchen, ob in Astrozyten der Serotonin-Transporter (5-HT-Transporter, 5-HTT), der Brain-derived neurotrophic factor (BDNF), der Dopamin-Transporter oder die Stickstoffmonoxyd-Synthase III (endotheliale Stickstoffmonoxid-Synthase, eNOS) gebildet werden und falls ja, ob sich deren Expression durch Applikation von Antidepressiva ändert. Die aus Rattenhirnen gewonnenen Astrozytenkulturen wurden hierfür entweder mit dem trizyklischen Antidepressivum Imipramin, dem selektiven Serotoninrückaufnahmeinhibitor Escitalopram oder zur Kontrolle mit Kochsalzlösung inkubiert. Nachdem die entsprechende mRNA aus den behandelten Astrozytenkulturen extrahiert wurde, ist sie in cDNA translatiert und mit Hilfe der quantitativen Real-Time PCR quantifiziert worden. Durch Vergleich der Expression des zu untersuchenden Gens mit der Expression der Housekeeping-Gene 18s-rRNA, Glycerinaldehyddehydrogenase (GAPDH) und Acidic ribosomal phosphoprotein (ARP) wurden Ungenauigkeiten bei der cDNA-Synthese ausgeglichen und die Daten normalisiert. Die rechnerische Auswertung der quantitativen Real-Time PCR erfolgte unter Verwendung der Ct-Werte unter Zuhilfenahme der geNORM Software. Die Ergebnisse zeigen eine signifikant erhöhte BDNF-Expression nach Imipramingabe. Hierbei zeigen bei den getrennten Untersuchungen der jeweiligen mRNA Chargen die mit 100µM Imipramin behandelten Astrozytenkulturen stärker signifikante Ergebnisse, als die mit 50µM Imipramin behandelten Astrozytenkulturen. Werden alle Proben, die mit der jeweiligen Imipraminkonzentration 4 Stunden inkubiert wurden, zusammen analysiert und mit den jeweiligen Kontrollen verglichen, zeigt sich sowohl bei der Behandlung mit 50µM Imipramin als auch mit 100µM Imipramin eine signifikante Steigerung der BDNF Expression. Escitalopram stimulierte die BDNF-Expression zwar ebenfalls nominell, jedoch war der Effekt nicht signifikant. Des Weiteren konnte eine deutliche Expression von 5-HTT-mRNA in Astrozytenkulturen nachgewiesen werden. Jedoch hatte keines der Antidepressiva einen signifikanten Effekt auf die 5-HTT-Expression. Es konnten weder in den behandelten, noch in den unbehandelten Astrozytenkulturen DAT oder NOS-III nachgewiesen werden. / Melancholia, loneliness, lack of interest: 2-7% of world population are ruled by these feelings. In Germany, 4 million inhabitants suffer from depression. Two third of this population are under medical treatment, but only half of these patients are diagnosed and medicated correctly. Reasons are difficulties in finding the exact diagnosis on the one hand and the vague aetiology and complex effects of antidepressants on the other. The origin of a depressive episode has multiple reasons, especially genetic components are considered to play an important role. Neurobiological investigations of the molecular and biochemical backgrounds of depressive episodes centre on three hypotheses: The dysbalance hypothesis of neurotransmitters (monoamine hypothesis), the hypothesis of activated hypothalamus-pituitary-adrenal axis and the neurotrophin hypothesis. In this context, the hypothesis of activated hypothalamus-pituitary-adrenal axis deals with the dysregulation and over-stimulation of the hypothalamus-pituitary-adrenal axis and the following elevated cortisol-secretion. The monoamine hypothesis of depressive episodes postulates a dysfunction of serotonergic, noradrenergic and dopaminergic systems. The neurotrophin hypothesis refers to the cyclic adenosine monophosphate (cAMP) second messenger system, activated by antidepressants. Cyclic adenosine monophosphate activates the cAMP dependent protein kinase (PKA) that phosphorylates and consequently stimulates the transcription factor cAMP response element binding protein (CREB). Activated CREB enhances the transcription of numerous genes, including the brain derived neurotrophic factor (BDNF) that is among others regulating neurotransmitters and influences neuronal survival, differentiation and plasticity. Astrocytes are part of the macroglia in central nervous system and form the major population of glial cells. They are considered to be responsible for homeostasis of potassium and the regulation of synaptic transmission and neurovascular linkage. Furthermore, astrocytes take part in forming glial cicatrixes, induction of blood-brain-barrier and neuronal survival. In the course of investigating the effects of antidepressants, the centre of interest has focused on astrocytes and their contribution to antidepressant therapy. The aim of this dissertation was to study, if the serotonin transporter (5-HTT), the brain derived neurotrophic factor (BDNF), the dopamin transporter or the nitric oxide synthase III (eNOS) is synthesised in astrocytes and in case of, if their expression is modulated by antidepressants. The astrocyte cultures, gained from rats’ brains, were incubated with the tricyclic antidepressant imipramine, the selective serotonin reuptake-inhibitor escitalopram or sodium chloride solution. After extracting the corresponding mRNA from the astrocyte cultures, it was translated to cDNA and quantified using the quantitative Real-Time PCR. Comparing the expression of the gene of interest with the expression of the housekeeping genes 18s-rRNA, glyceraldehydes phosphate dehydrogenase (GAPDH) and acidic ribosomal phosphoprotein (ARP), equated inexactness of cDNA synthesis and normalised the acquired data. The mathematical evaluation of the qRT-PCR based on the Ct-figures with the assistance of geNORM software. The results show a significantly elevated BDNF expression after imipramine administration. mRNA batches of astrocyte cultures incubated with 100µM imipramine presented more significant results than mRNA batches of astrocyte cultures incubated with 50µM imipramine. Analysing all samples incubated for four hours with the corresponding concentration of imipramine and compared with the sodium chloride solution controls, a significant elevation of BDNF expression is detected in 50µM imipramine samples as well as in 100µM imipramine samples. Escitalopram stimulates the expression of BDNF nominally without showing significant effects. Furthermore, a clear expression of 5-HTT-mRNA in astrocyte cultures could be detected, but none of the antidepressants induced a significant effect on 5-HTT expression. Neither in medicated nor in control samples DAT or NOS-III were detected.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-02-26T11:26:20Z No. of bitstreams: 1 izabellaliguoricorsinovabo.pdf: 625553 bytes, checksum: cb3de105eafd87fb538ddfcec36c8d50 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-03-03T13:37:11Z (GMT) No. of bitstreams: 1 izabellaliguoricorsinovabo.pdf: 625553 bytes, checksum: cb3de105eafd87fb538ddfcec36c8d50 (MD5) / Made available in DSpace on 2016-03-03T13:37:12Z (GMT). No. of bitstreams: 1 izabellaliguoricorsinovabo.pdf: 625553 bytes, checksum: cb3de105eafd87fb538ddfcec36c8d50 (MD5) Previous issue date: 2015-01-29 / Mundialmente a hepatite C crônica é uma das principais causas de hepatopatia crônica. No mundo ocidental, representa a principal causa de cirrose hepática, carcinoma hepatocelular e indicação de transplante hepático. Atualmente, o tratamento utilizado consiste na utilização de interferon alfa peguilado e ribavirina associado ou não aos novos inibidores da protease por 24 a 48 semanas dependendo do genótipo e do grau de fibrose hepática. Além da eficácia longe do ideal, o tratamento da hepatite C crônica é repleto de eventos adversos destacando-se os transtornos neuropsiquiátricos, sobretudo o episódio depressivo. No Brasil existem poucos estudos a respeito da incidência deste episódio na terapia dupla. Diante disso, a proposta deste estudo foi verificar a incidência e os fatores associados ao surgimento de episódio depressivo em pacientes com hepatite C crônica submetidos à terapia antiviral com Interferon peguilado alfa 2a ou 2b e ribavirina, além de avaliar o impacto do surgimento deste episódio sobre a resposta virológica sustentada. Foram incluídos 32 pacientes com Hepatite C Crônica, submetidos à terapia dupla em seguimento regular no Ambulatório de Hepatologia do Serviço de Gastroenterologia do HU/CAS-UFJF, no período de junho de 2012 a junho de 2014. A HADS (Escala Hospitalar de Ansiedade e Depressão) foi utilizada para rastreamento do episódio depressivo, aplicada no baseline e nas semanas 4, 12, 24, 48 e 4 semanas após a interrupção da terapia. O diagnóstico de episódio depressivo foi estabelecido nos pacientes com HADS ≥ 9. Estes foram submetidos ao BDI-II (Inventário de Depressão de Beck) para graduação do episódio depressivo em nível mínimo, leve, moderado e grave. Variáveis clínicas, laboratoriais, histológicas e sócio- demográficas de interesse foram obtidas. Destes pacientes, 25% desenvolveram episódio depressivo sendo o pico de incidência observado na semana 12 de terapia antiviral. O episódio depressivo foi moderado em 87% dos pacientes. Não foi possível identificar preditores de episódio depressivo. A taxa de resposta virológica sustentada foi 75% e 67% nos pacientes com e sem episódio depressivo, respectivamente (p = 0,66). Os resultados permitem concluir que a incidência de episódio depressivo em portadores de hepatite C Crônica submetidas a terapia antiviral é elevada; não foi possível demonstrar fatores relacionados ao aparecimento deste; a presença de episódio depressivo não influenciou a taxa de resposta virológica sustentada. / Chronic Hepatitis C is one of the main causes of chronic liver disease around the world. In the west, it represents the leading cause of liver cirrhosis, hepatocellular carcinoma and indication of liver transplantation. Currently, the usual treatment consists on the use of pegylated interferon alpha and ribavirin, associated or not with the new protease inhibitors, for 24 to 48 weeks, depending on the genotype and the degree of liver fibrosis. Besides the far from ideal effectiveness, the treatment of chronic Hepatitis C is full of adverse events, of which the neuropsychiatric disorders stand out, especially the depressive episode. In Brazil, there are few studies about the incidence of that episode on double therapy. As such, the goal of this study was to verify the incidence and the factors associated with the appearance of the depressive episode in chronic Hepatitis C patients subjected to antiviral therapy with pegylated Interferon alpha 2a or 2b and ribavirin, as well as to evaluate the impact of the appearance of that episode over the sustained viral response. 112 chronic Hepatitis C patients were included, 80 of which were antiviral treatment-naive (control group) and 32 subjected to double therapy (treatment group), regularly followed at the Hepatology Clinic of the Gastroenterology Service of HU/CAS-Universidade Federal de Juiz de Fora, between June 2012 and June 2014. The HADS (Hospital Anxiety and Depression Scale) was used for tracking the depressive episode in both groups, being applied at baseline, at weeks 4, 12, 24 and 48 and 4 weeks after interruption of the therapy on the treatment group. The diagnosis of depression was established at patients with HADS ≥ 9. These were subjected to BDI-II (Beck Depression Inventory) for gradation of the depressive episode in levels minimum, light, moderate and severe. Clinical, laboratory, histological and sociodemographic variables of interest were obtained. On the treatment group, 25% of the patients developed depressive episode, with the peak incidence observed at week 12 of antiviral therapy. The depressive episode was moderate on 87% of the patients. It was not possible to identify predictors for the depressive episode. The sustained viral response rate was 75% and 67% on patients with and without depressive episode, respectively (p = 0,66). The results allow concluding that the incidence of depression on chronic Hepatitis C carriers subjected to antiviral therapy is high and was similar to what the literature describes; it was not possible to demonstrate factors related to the appearance of depression; the presence of depression did not influence the sustained viral response rate.

No description available.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jana Rambousková Supervisor: Prof. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Pharmacotherapy of mood disorder This diploma thesis deals with the characterization of mood disorders concentrating especially on depression disorders. It presents the classification of mood disorders according to classification MKN-10. The diploma thesis presents patophysiology of depression disorders, their causes, symptoms and progress. It analyses the choice of pharmacotherapy in depression disorders and bipolar affective disorder. It describes individual groups of antidepressants and drugs used for treatement of bipolar affective disorder. It analyses their mechanism of action, indications, contraindications and adverse effects. At the end of diploma thesis states the other use of antidepressants in non- psychiatric indications.

Objetivos: Estudar a confiabilidade e validade de uma versão brasileira dos módulos Episódio Depressivo Maior (EDM) e Transtorno de Ansiedade Generalizado (TAG) do Mini International Neuropsychiatric Interview TRACKING (MINI-TRACKING); comparar a evolução de pacientes com diagnóstico de EDM e TAG seguidos por equipes de Estratégia de Saúde da Família (ESF) com acesso ao modelo de Cuidado Colaborativo (CC) em Saúde Mental versus um grupo de pacientes seguidos por equipes sem acesso ao CC. Metodologia: O estudo envolveu quatro equipes de ESF vinculadas à Faculdade de Medicina de Ribeirão Preto (FMRP), sendo duas com acesso ao CC e duas sem CC. Um total de 147 pacientes foram entrevistados com o objetivo de rastrear transtornos mentais com a aplicação do WHO-5 e do COOP-WONCA Quadro Sentimentos. Após a confirmação diagnóstica de EDM e/ou TAG, com a entrevista MINI, 42 pacientes foram selecionados e concordaram em participar da pesquisa. Estes pacientes foram acompanhados por doze meses por um médico de família (MF), que aplicou periodicamente a cada oito a doze semanas os módulos EDM e/ou TAG do MINI-TRACKING. Para avaliação da fidedignidade e da validade concorrente, um psiquiatra (cego quanto ao diagnóstico do MF e quanto a qual equipe seguia o paciente) aplicou, com intervalo máximo de 72h do MF, os mesmos módulos do MINI-TRACKING, o PHQ-9 e/ou o GAD-7. Resultados: Não foi encontrada diferença estatisticamente significativa entre os pacientes das equipes com e sem CC no que se refere as características clínicodemográficas. Os itens individuais dos dois módulos do MINI-TRACKING mostraram boa fidedignidade inter-avaliadores (Kappa entre 0,78 e 0,98), bem como seus escores totais (Coeficiente Intra-classe de 0,996 e 0,993 para EDM e TAG, respectivamente). Os módulos EDM e TAG mostraram também boa validade concorrente com as escalas PHQ-9 e GAD-7 (coeficiente de Pearson 0,994 e 0,976, respectivamente). Trinta pacientes (quinze de equipes com CC e 15 de equipes sem CC) completaram as cinco avaliações no decorrer de um ano de seguimento. A ANOVAmr destes pacientes mostrou diferenças significativas no fator tempo e na interação tempo x intervenção, com diminuição significativamente maior dos escores do MINI-TRACKING nos pacientes seguidos pelas equipes com CC. Conclusão: Os módulos EDM e TAG do MINI-TRACKING são uma opção confiável para o seguimento de pacientes com estes diagnósticos. Este estudo também mostrou, de forma preliminar, que o CC em saúde mental é uma estratégia eficaz na redução de sintomas dos pacientes com EDM e TAG na Atenção Primária. / Objectives: To study the reliability and validity of a Brazilian version of the Mini International Neuropsychiatric Interview - TRACKING (MINI-TRACKING) modules for Major Depressive Episode (MDE) and Generalized Anxiety Disorder (GAD); To compare the outcomes of patients diagnosed with MDE and GAD followed by teams of the Family Health Strategy (FHS) with access to the Mental Health Collaborative Care model (CC) versus a group of patients followed by teams without access to CC. Methodology: The study involved four FHS teams of the Faculty of Medicine of Ribeirão Preto (FMRP), two of them with access to CC and two without it. A total of 147 patients were tracked for mental disorders with the application of the WHO-5 and the COOP-WONCA Chart Feelings. After confirming the diagnosis of MDE and/or GAD using the MINI interview, 42 patients were selected and agreed to participate. These patients were followed for twelve months by a family physician (FP), who applied regularly every eight to twelve weeks the MDE and/or the GAD MINI-TRACKING modules. To assess the reliability and concurrent validity, a psychiatrist (blind to the diagnosis and to which team the patient was followed) also applied the same modules of the MINI-TRACKING, the PHQ-9 and/or the GAD-7, with a maximum interval of 72 hours of the FP. Results: There was no statistically significant difference between the patients with and without CC teams regarding demographic and clinical characteristics. The individual items of the two MINI-TRACKING modules showed good inter-rater reliability (kappa between 0.78 and 0.98), as well as their total scores (Intra-class coefficient of 0.996 and 0.993 for MDE and GAD, respectively). The MDE and GAD modules also showed good concurrent validity with PHQ-9 and GAD-7 scales (Pearson coefficient 0.994 and 0.976, respectively). Thirty patients (fifteen with CC and 15 without CC) completed the five assessments during one year of follow up. The repeated-measures analysis of variance (rmANOVA) showed significant differences in the time factor and the interaction time x intervention, decrease significantly higher of the MINI-TRACKING scores in the patients followed by teams with CC. Conclusion: MINI-TRACKING MDE and GAD modules are a reliable option for following patients with these diagnoses. This study also showed, preliminarily, that CC in Mental Health is an effective strategy in reducing symptoms in Primary Care patients with MDE and GAD.

INTRODUÇÃO: A depressão bipolar (DB) é uma condição altamente prevalente associada a déficits cognitivos que persistem mesmo na fase eutímica da doença. Os tratamentos farmacológicos para DB podem agravar ainda mais o comprometimento cognitivo, destacando a necessidade de desenvolver intervenções que tenham segurança cognitiva. A Estimulação Magnética Transcraniana \'profunda\' através de bobina H1 (EMTr-H1) é uma nova modalidade de neuromodulação com eficácia estabelecida para a depressão unipolar. Este é o primeiro estudo em caráter exploratório e controlado por placebo, a avaliar os efeitos cognitivos da EMTr-H1 em pacientes com DP resistente ao tratamento. MÉTODO: Quarenta e três pacientes foram randomizados para receber 20 sessões de EMTr-H1 ativa (55 séries de estímulos direcionados à área pré frontal esquerda, a 18Hz e 120% de intensidade do limiar motor em repouso) ou de EMTr-H1 placebo, em um ensaio duplo-cego, controlado por estimulação simulada. Uma bateria de avaliação neuropsicológica contendo 20 testes cognitivos, agrupados em seis domínios cognitivos (atenção e velocidade de processamento, memória de trabalho e função executiva, controle inibitório, linguagem, memória verbal imediata e memória verbal de longo prazo), foi realizada imediatamente antes do início das sessões de EMTr-H1 (avaliação basal - semana 0) e após 4 (20ª e última sessão - semana 4) e 8 semanas (seguimento de mais 4 semanas sem novas intervenções - semana 8) do início deste estudo. Sintomas depressivos e maníacos também foram avaliados. A medida clínica de desfecho primária foi à redução percentual do escore basal da Escala de Hamilton para avaliação da depressão com 17 itens (HDRS-17) após 20 sessões de estimulação (semana 4). A medida de segurança durante as 8 semanas incluiu, além da Escala de Mania de Young (YMRS) para avaliar ciclagens de mania emergentes possivelmente relacionados ao tratamento (TEMS), principalmente, uma bateria de testes de avaliação neuropsicológica, que avaliou a possibilidade de sequelas e/ou reparações cognitivas em relação ao método. RESULTADOS: Entre os 50 pacientes que iniciaram o estudo, 2 do grupo placebo EMTr-H1 e 5 do grupo EMTr-H1 ativo, desistiram de participar do ensaio e não completaram as avaliações, sendo excluídos da análise (\"dropouts\"), portanto, 43 pacientes finalizaram o estudo. O grupo EMTr-H1 ativo apresentou uma resposta clinica antidepressiva superior ao placebo na semana 4 (diferença favorecendo EMTr-H1=4,88; 95% CI=0,43 a 9,32, p=0,03), mas não nas semanas de seguimento. Houve também uma tendência para maiores taxas de resposta no grupo ativo (48%) vs. placebo (24%) (OR=2,92; 95% CI=0,87 a 9,78, p=0,08). As taxas de remissão não foram estatisticamente diferentes. Não foram observados episódios de TEMS. Foi constatada uma melhoria cognitiva em relação a todos os domínios cognitivos, mas que ocorreu ao longo do tempo e independentemente do grupo de intervenção e da melhora da depressão. Não foi encontrada correlação entre a melhora da depressão e da cognição. LIMITAÇÕES: Ausência de um grupo controle saudável. CONCLUSÕES: A EMTr \'profunda através da bobina H1 é uma terapia antidepressiva de adição potencialmente eficaz e bem tolerada em pacientes com depressão bipolar resistente que receberam farmacoterapia adequada. Os resultados cognitivos deste estudo exploratório fornecem evidências sobre a segurança cognitiva da EMTr-H1 para pacientes com DB. Não foram observados supostos efeitos deletérios e nem pró-cognitivos da EMTr-H1 na DB, mas pesquisas adicionais se fazem necessárias por meio de outros estudos similares e que contemplem a cognição / INTRODUCTION: Bipolar depression (BD) is a highly prevalent condition associated with marked cognitive deficits that persist even in the euthymic phase of the illness. Pharmacological treatments for BD might further aggravate cognitive impairment, highlighting the need of developing interventions that have cognitive safety. \'Deep\' H1-coil Transcranial Magnetic Stimulation (H1-rTMS) is a new modality of neuromodulation with established efficacy for unipolar depression. This is the first exploratory, placebo-controlled study evaluating the cognitive effects of rTMS in patients with treatment-resistant bipolar depression. METHODS: Fourty-three patients were randomized to receive 20 sessions of active (55 trains directed to the left prefrontal area, 18Hz, 120% resting motor threshold intensity) or sham rTMS within a double-blind, sham-controlled trial. A battery of neuropsychological assessment with 20 cognitive tests, grouped in 6 domains (attention and processing speed, working memory and executive function, inhibitory control, language, immediate verbal memory, and long-term verbal memory) was performed at baseline (week 0) and after 4 (20th and last session - week 4) and 8 weeks (follow-up of 4 weeks without further intervention - week 8) of trial onset. Depressive and manic symptoms were also evaluated. The primary clinical outcome measure was percentage reduction of the baseline score of the Hamilton Scale for assessment of depression with 17 items (HDRS-17) after 20 stimulation sessions (week 4). The safety measure during the 8 weeks included, in addition to the Young Mania Scale (YMRS) wich evaluated the emergent mania possibly related to treatment (TEMS), mainly a battery of neuropsychological evaluation tests, which evaluated the possibility of sequelae or cognitive repairs in relation to the method. RESULTS: Among the 50 patients who started the study, 2 of the sham H1-rTMS group and 5 of the active H1-rTMS group, gave up participating in the trial and did not complete the assessments, being excluded from the analysis (\"dropouts\"), therefore, 43 patients completed the study. The active H1-rTMS had an antidepressant clinical response higher than placebo at week 4 (difference favoring H1-rTMS=4.88; 95% CI=0.43 to 9.32, p=0.03) but not at weeks of follow-up. There was also a trend for greater response rates in the active (48%) vs. sham (24%) groups (OR=2.92; 95% CI=0.87 to 9.78, p=0.08). Remission rates were not statistically different. No TEMS episodes were observed. A cognitive improvement was observed in all cognitive domains, but it occurred over time and independently of the intervention group and depression improvement. No correlation was found between improvement of depression and cognition. LIMITATIONS: Absence of healthy control group. CONCLUSION: Deep H1-rTMS is a potentially effective and well-tolerated add-on antidepressive therapy in resistant bipolar depressed patients to received adequate pharmacotherapy. The cognitive results of this exploratory study provide evidence on the cognitive safety of H1-coil rTMS for BD patients. No deleterious or pro-cognitive effects of H1-rTMS in BD have been observed, but further research is needed through other similar studies that contemplate cognition