Posibles mecanismos de acción de la terapia electroconvulsiva en trastornos afectivos: revisión de la evidencia disponible en investigación con seres humanos / Putative mechanisms of action of electronvulsive therapy in affective disorders, a review

The mechanisms of action (MA) of electroconvulsive therapy (ECT) in affective disorders are poorly understood. We synthesized and discussed the evidence provided by primary studies and systematic reviews in humans. There are differences in the methylation of candidate genes involved in the response to ECT. Functioning of the hippocampal serotonin receptor 5-HT1B is associated with the response in patients with major depressive disorder (PMDD), while the striatal dopamine transporter would participate in the response of PMDD and in patients with bipolar disorders (BD). The only neurotrophic factor associated with ECT response was vascular endothelial growth factor. In BD, some oxidative stress metabolites had a clinical correlation, while tryptophan metabolism showed a clinical association in BD and PMDD. Furthermore, in PMDD, some neurodegeneration markers were implicated in the MA of ECT. There were no other biological dimensions associated with BD. In PMDD, multiple inflammatory mediators were associated with the clinical response (natural killer cells, tumor necrosis and growth factors, and interleukins 1, 4, 6, 10,1β). Likewise, some structures and circuits consistently involved at the morphological and functional level are the default mode network, cognitive control networks, frontal, temporal, cingulate, occipital and temporal cortices, frontal, temporal, precentral, fusiform and left angular gyri, hippocampus, thalamus and amygdala. Investigations are mostly focused on PMDD, are observational, and their samples limited, but they show relatively consistent results with clinical significance.

Posibles mecanismos de acción de la terapia electroconvulsiva en esquizofrenia: revisión de la evidencia disponible en investigación con seres humanos / A review about the putative mechanisms of action of electroconvulsive therapy in schizophrenia in human research

Electroconvulsive therapy (ECT) has multiple uses in psychiatry, but its mechanisms of action (MA) in patients with schizophrenia (PS) are poorly understood. We synthesize and discuss the available evidence in this regard. We conducted a search for primary human studies and systematic reviews searching MA of ECT in PS published in PubMed/Medline, SciELO, PsycInfo, and the Cochrane Library, including 24 articles. Genetic findings are scarce and inconsistent. At the molecular level, the dopaminergic and GABAergic role stands out. The increase in brain derived neurotrophic factor (BDNF) after ECT, is a predictor of positive clinical outcomes, while the change in N-acetyl aspartate levels would demonstrate a neuroprotective role for ECT. This intervention would improve inflammatory and oxidative parameters, thereby resulting in a symptomatic improvement. ECT is associated with an increase in functional connectivity in the thalamus, right putamen, prefrontal cortex and left precuneus, structures that play a role in the neural default mode network. A decrease in connectivity between the thalamus and the sensory cortex and an enhanced functional connectivity of the right thalamus to right putamen along with a clinical improvement have been reported after ECT. Moreover a volumetric increase in hippocampus and insula has been reported after ECT. These changes could be associated with the biochemical pathophysiology of schizophrenia. Most of the included studies are observational or quasi-experimental, with small sample sizes. However, they show simultaneous changes at different neurobiological levels, with a pathophysiological and clinical correlation. We propose that the research on ECT should be carried out from neurobiological dimensions, but with a clinical perspective.

The maintenance of modified electroconvulsive therapy combined with risperidone is better than risperidone alone in preventing relapse of schizophrenia and improving cognitive function / Manutenção de eletroconvulsoterapia modificada combinada com risperidona é melhor do que a risperidona isoladamente na prevenção de recidivas de esquizofrenia e melhoras da função cognitiva

ABSTRACT Objective To evaluate the effect of maintenance modified electroconvulsive therapy (MECT) on schizophrenic patients. Methods From June 2012 to June 2014, 62 patients with schizophrenia, who had recovered from a successful course of acute MECT, were recruited. Thirty-one patients received maintenance MECT and risperidone, as the experimental group. Another 31 patients were enrolled in the control group, and received risperidone only. The effects on cognitive functions, clinical symptoms and relapse rate were determined. Results Patients in the experimental group had a lower relapse rate and longer relapse-free survival time than the controls. Relative to the baseline evaluation, patients showed statistically significant improvement in verbal memory and visual memory. At the final assessment, the scores of verbal and visual memory were remarkably lower in the experimental group than the controls but there was no significant difference in other tests. Conclusion Maintenance MECT plus medication is superior to medication alone in preventing relapse and improving cognitive function.

RESUMO Objetivo Avaliar o efeito da manutenção de eletroconvulsoterapia modificada (ECTM) em pacientes com esquizofrenia. Métodos Entre junho de 2012 a junho de 2014, 62 pacientes, com esquizofrenia e que apresentaram recuperação bem-sucedida após ECTM aguda, foram recrutados. Um grupo experimental de trinta e um pacientes recebeu ECTM de manutenção e risperidona. Os demais pacientes foram incluídos no grupo controle, recebendo apenas a risperidona. Determinou-se os efeitos sobre as funções cognitivas, os sintomas clínicos e a taxa de recidiva. Resultados Os pacientes do grupo experimental tiveram menor taxa de recidiva e maior tempo de sobrevida livre de recidiva do que os do grupo controle. Em relação à avaliação inicial, os pacientes apresentaram melhora estatisticamente significativa da memória verbal e da memória visual. Na avaliação final, os escores de memória verbal e visual foram extraordinariamente menores no grupo experimental do que no grupo controle, mas não se observou diferenças significativas em outros testes. Conclusão A ECTM de manutenção combinada à medicação é superior ao uso apenas de medicação na prevenção de recidivas e na melhora da função cognitiva.

Electroconvulsive therapy in Parkinson´s disease / A eletroconvulsoterapia na doença de Parkinson

Purpose To analyze the effectiveness of electroconvulsive therapy for the management of depression and/or psychosis refractory to drug therapy in patients with Parkinson disease.Methods A retrospective study was carried out including patients treated with electroconvulsive therapy during the period between 2002 and 2013. A review of the literature was performed.Results A total of 27 patients were included. In regards to the neuropsychiatric diagnosis, 14 patients had major depression, 12 patients had both psychosis and depression, and only one patient had isolated psychosis. The mean number of electroconvulsive therapy sessions was 12 ± 2.8. After electroconvulsive therapy, all patients showed a statistically significant improvement in the Brief Psychiatric Rating scale (reduction of 52% points) and Hamilton Depression Rating Scale (reduction of 50% points) independent of the presence of psychosis, depression or both.Conclusion Electroconvulsive therapy is effective for the treatment of refractory neuropsychiatric symptoms in Parkinson’s disease.

Propósito Analisar a eficácia da eletroconvulsoterapia para o tratamento da depressão e/ou psicoses refratária ao tratamento medicamentoso em pacientes com doença de Parkinson.Métodos Um estudo retrospectivo foi realizado com pacientes tratados com a eletroconvulsoterapia, durante o período entre 2002 e 2013. Uma revisão da literatura foi realizada.Resultados Um total de 27 pacientes foram incluídos. Em relação ao diagnóstico neuropsiquiátrico, 14 pacientes tinham depressão maior, 12 pacientes tiveram tanto psicoses e depressão, e apenas um paciente tinha isolado psicoses. O número médio de sessões de eletroconvulsoterapia foi de 12 ± 2,8. Após a eletroconvulsoterapia, todos os pacientes apresentaram uma melhora estatisticamente significativa no Brief Psychiatric Rating Scale (redução de 52% de pontos) e Hamilton Depression Rating Scale (redução de 50% de pontos), independente da presença de psicose, depressão ou ambos.Conclusão Eletroconvulsoterapia é eficaz para o tratamento de sintomas neuropsiquiátricos refractários na doença de Parkinson.

Variation of plasma cortisol levels in patients with depression after treatment with bilateral electroconvulsive therapy / Variação de cortisol plasmático em pacientes deprimidos após tratamento com eletroconvulsoterapia bilateral

Introduction: More than 60 years after the introduction of modern psychopharmacology, electroconvulsive therapy (ECT) continues to be an essential therapeutic modality in the treatment of mental disorders, but its mechanism of action remains unclear. Hormones play an essential role in the development and expression of a series of behavioral changes. One aspect of the influence of hormones on behavior is their potential contribution to the pathophysiology of psychiatric disorders and the mechanism of action of psychotropic drugs and ECT. Objective: We measured blood levels of the hormone cortisol in patients with unipolar depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and compared results with levels found in healthy adults. Method: Blood cortisol levels were measured before the beginning of treatment with ECT, at the seventh session, and at the last session, at treatment completion. Depression symptoms were assessed using the Beck Depression Inventory (BDI). Results: Cortisol levels remained stable in both men and women between the seventh and the last sessions of ECT; values ranged from 0.686±9.6330 g/dL for women, and there was a mean decrease of 5.825±6.0780 g/dL (p = 0.024). Mean number of ECT sessions was 12. After the seventh and the last ECT sessions, patients with depression and individuals in the control group had similar cortisol levels, whereas BDI scores remained different. Conclusion: Cortisol levels decreased during ECT treatment. ECT seems to act as a regulator of the hypothalamic-pituitaryadrenal axis. .

Introdução: Mais de 60 anos após a introdução da moderna psicofarmacologia, a eletroconvulsoterapia (ECT) continua essencial para o tratamento de distúrbios mentais, mas seu mecanismo de ação ainda não é totalmente conhecido. Certos hormônios têm um papel fundamental no desenvolvimento e expressão de uma série de alterações comportamentais. Um aspecto da influência dos hormônios nos comportamentos é sua contribuição potencial para a patofisiologia dos distúrbios psiquiátricos e o mecanismo de ação de psicotrópicos e da ECT. Objetivo: Os níveis do hormônio cortisol no sangue foram medidos em pacientes com depressão unipolar classificados de acordo com a 4ª edição do Manual Estatístico e Diagnóstico de Transtornos Mentais (DSM-IV), e os resultados foram comparados com os níveis encontrados em adultos saudáveis. Métodos: Os níveis de cortisol no sangue foram medidos antes do início do tratamento com ECT, na sétima e na última sessão, após a conclusão do tratamento. Os sintomas de depressão foram avaliados usando o Inventário de Depressão de Beck (BDI). Resultados: Os níveis de cortisol permaneceram estáveis tanto nos pacientes masculinos quanto femininos entre a sétima e a última sessão de ECT; os valores variaram 0,686±9,6330 g/ dL entre as pacientes femininas, e houve uma diminuição de 5,825±6,0780 g/dL (p = 0,024). O número médio de sessões de ECT foi 12. Após a sétima e a última sessão de ECT, os níveis de cortisol nos pacientes com depressão e nos indivíduos no grupo controle foram semelhantes, enquanto os resultados da escala BDI permaneceram diferentes. Conclusão: Os níveis de cortisol diminuíram durante o tratamento com ECT. A ECT parece atuar como reguladora do eixo hipotalâmico-hipofisário-adrenal. .

Twenty years of electroconvulsive therapy in a psychiatric unit at a university general hospital / Vinte anos de eletroconvulsoterapia em enfermaria psiquiátrica de hospital geral universitário

Objective: To describe the sociodemographic and clinical profile of patients who underwent electroconvulsive therapy (ECT) at a university general hospital. Method: In this retrospective study, records from all patients undergoing ECT between January 1988 and January 2008 at the psychiatric unit of the general hospital of Universidade Estadual de Campinas (UNICAMP) were reviewed. Telephone contact was made with patients/relatives to collect follow-up data. Results: A total of 200 charts were reviewed. The majority of patients were women, with a mean age of 39 years, and history of psychiatric hospitalization. The main indications for ECT were depression and catatonia. Complications were observed in less than half of the cases, and most were temporary and not severe. There was a good psychiatric outcome for 89.7% of the patients, especially for catatonic patients (100%, p = 0.02). Thirty-four percent of the cases were later contacted by telephone calls, at a mean of 8.5 years between the procedure and the contact. Among these, three (1.5%) reported persistent memory disorders and 73% considered ECT a good treatment. Conclusion: ECT has been performed according to international guidelines. In the vast majority of cases, undesirable effects were temporary and not severe. Response to ECT was positive in most cases, particularly in catatonic patients.

Objetivo: Descrever o perfil sociodemográfico e clínico de pacientes submetidos a eletroconvulsoterapia (ECT) em um hospital geral universitário. Método: Neste estudo retrospectivo, foram revisados os prontuários de todos os pacientes submetidos a ECT entre janeiro de 1988 e janeiro de 2008 na unidade psiquiátrica do hospital geral da Universidade Estadual de Campinas (UNICAMP). Os pacientes/familiares foram contatados por telefone para a coleta de dados de seguimento. Resultados: Um total de 200 prontuários foram revisados. A maioria dos pacientes era do sexo feminino, com uma idade média de 39 anos e história de hospitalização psiquiátrica prévia. As principais indicações para ECT foram depressão e catatonia. Complicações foram observadas em menos de metade dos casos, e a maioria delas teve caráter temporário e não grave. Houve resultado psiquiátrico favorável em 89,7% dos pacientes, especialmente os catatônicos (100%, p = 0,02). Trinta e nove por cento dos casos foram contatados por telefone, a uma média de 8,5 anos decorridos entre o procedimento e o contato. Entre estes, três (1,5%) relataram transtornos amnésticos persistentes e 73% consideraram a ECT um bom tratamento. Conclusão: A ECT foi realizada de acordo com diretrizes internacionais. Na grande maioria dos casos, efeitos indesejáveis foram temporários e não graves. A resposta à ECT foi positiva na maioria dos casos, especialmente em pacientes catatônicos.

Neuromodulation approaches for the treatment of major depression: challenges and recommendations from a working group meeting / Estratégias de neuromodulação para o tratamento da depressão maior: desafios e recomendações de uma força-tarefa

The use of neuromodulation as a treatment for major depressive disorder (MDD) has recently attracted renewed interest due to development of other non-pharmacological therapies besides electroconvulsive therapy (ECT) such as transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). METHOD: We convened a working group of researchers to discuss the updates and key challenges of neuromodulation use for the treatment of MDD. RESULTS: The state-of-art of neuromodulation techniques was reviewed and discussed in four sections: [1] epidemiology and pathophysiology of MDD; [2] a comprehensive overview of the neuromodulation techniques; [3] using neuromodulation techniques in MDD associated with non-psychiatric conditions; [4] the main challenges of neuromodulation research and alternatives to overcome them. DISCUSSION: ECT is the first-line treatment for severe depression. TMS and tDCS are strategies with a relative benign profile of side effects; however, while TMS effects are comparable to antidepressant drugs for treating MDD; further research is needed to establish the role of tDCS. DBS and VNS are invasive strategies with a possible role in treatment-resistant depression. In summary, MDD is a chronic and incapacitating condition with a high prevalence; therefore clinicians should consider all the treatment options including invasive and non-invasive neuromodulation approaches.

O uso de técnicas de neuromodulação para o tratamento do transtorno depressivo maior (TDM) tem despertado um renovado interesse nos últimos anos com o desenvolvimento de outras intervenções não-farmacólogicas além da eletroconvulsoterapia (ECT), como a estimulação magnética transcraniana (EMT), a estimulação transcraniana por corrente continua (ETCC), a estimulação cerebral profunda (DBS) e a estimulação de nervo vago (VNS). MÉTODO: Nós organizamos um grupo de trabalho com vários pesquisadores para discutir os avanços recentes e os principais desafios para o uso da neuromodulação no tratamento do TDM. RESULTADOS: O estado-da-arte da neuromodulação foi revisado e discutido em quatro seções: [1] epidemiologia e fisiopatologia do TDM; [2] uma revisão das técnicas de neuromodulação; [3] o uso das técnicas de neuromodulação na depressão que ocorre associada ou em virtude de condições não-psiquiátricas; [4] os principais desafios da pesquisa na neuromodulação e alternativas para superá-los. DISCUSSÃO: ECT é o tratamento de primeira linha para depressão grave. EMT e ETCC são estratégias com um perfil benigno de efeitos adversos; contudo, enquanto os efeitos da EMT são comparáveis ao das drogas antidepressivas para o tratamento da TDM, a eficácia da ETCC ainda precisa ser estabelecida por mais pesquisas clínicas. DBS e VNS são intervenções invasivas com um papel possível para a depressão refratária. Em resumo, TDM é uma condição crônica, incapacitante e de alta prevalência; portanto na prática clínica todas as opções de tratamento possíveis, incluindo as farmacológicas e não-farmacológicas, devem ser consideradas.

Aspectos bioéticos relacionados con el tratamiento del electroshock en pacientes psiquiátricos / Electroconvulsive therapy

El electroshock o terapia electroconvulsivante (TEC) ha sido considerado uno de los tratamientos psiquiátricos más controversiales desde que comenzó su aplicación, aceptado por unos y negado por otros, en el intervienen criterios de disciplinas tales como la Filosofía, la Ética, los aspectos medicolegales y la religión. Este trabajo pretende, en su revisión y análisis, evidenciar un viejo conflicto no resuelto aún en el cual se interrelacionan paciente, familiares y profesional médico además de una terapéutica específica (terapia electroconvulsivante), tema aún muy debatido en la actualidad por los mitos que existen en torno a él, para cuya solución se requieren nuevos estudios más serios y cuidadosos en el campo de las neurociencias por ser este un nuevo desafío en el estudio del cerebro.

Electroshock or electroconvulsive therapy (TEC) has been considered one of the most controversial psychiatric treatment since the beginning of its application, being accepted by some professionals and denied by others, where criteria and disciplines such as Philosophy and Ethics; medical legal aspects and Religion interfere. This work intends through its revision and analysis to evidence an old conflict not resolved in which patient, relatives and medical personnel in addition to this therapy are involved. This therapy constitutes a so much discussed matter at present time due to the myths that surrounded it and requires new more serious and careful studies carry out on the Neurosciences field due to the fact that this treatment means a new challenge on the study of the brain.

Terapias somáticas para transtornos psiquiátricos resistentes ao tratamento / Somatic therapies for treatment-resistant psychiatric disorders

OBJETIVO: O presente artigo é uma revisão do conhecimento atual relativo às terapias somáticas em psiquiatria, com foco em transtornos psiquiátricos resistentes ao tratamento usual. MÉTODO: Foi realizada uma pesquisa computadorizada da literatura no Medline utilizando as palavras "eletroconvulsoterapia", "estimulação magnética transcraniana", "terapia magnética convulsiva", "estimulação do nervo vago" e "estimulação cerebral profunda", com todos os termos traduzidos para o idioma inglês. Referências listadas em cada artigo foram também analisadas. RESULTADOS: O desenvolvimento de novos tratamentos psiquiátricos não farmacológicos nas últimas décadas renovou o interesse em terapias somáticas. A despeito de a eletroconvulsoterapia continuar a ser o único tratamento somático com eficácia estabelecida, a estimulação magnética transcraniana, a terapia magnética convulsiva, a estimulação do nervo vago e a estimulação cerebral profunda são potencialmente novas modalidades de tratamento psiquiátrico. CONCLUSÕES: Novas modalidades de tratamento ainda padecem de falta de conhecimento cientifico adequado. Entretanto, estratégias somáticas ainda representam uma promessa como formas mais eficazes e seguras de tratamento psiquiátrico.

OBJECTIVE: This paper reviews the current knowledge of somatic treatment in psychiatry, with a focus on treatment-resistant psychiatric disorders. METHOD: A computerized search of the literature was conducted on Medline using the words "electroconvulsive therapy", "transcranial magnetic stimulation", "vagus nerve stimulation", "deep brain stimulation" and "magnetic seizure therapy". References from each paper were also screened. RESULTS: The development of new non-pharmacological psychiatric interventions in the past decades has renewed the clinical and research interest in somatic therapies. Although electroconvulsive therapy remains the only somatic treatment with undisputed efficacy, transcranial magnetic stimulation, magnetic seizure therapy, vagus nerve stimulation and deep brain stimulation all offer potential as novel means of psychiatric treatment. CONCLUSIONS: New treatment modalities still have an insufficient body of data. Notwithstanding, biological strategies continue to hold promise as a safer and more effective approach to psychiatric treatment.

Propofol frente a tiopental en la terapia electroconvulsiva / Propofol versus Thiopental in electroconvulsive therapy

Con el fin de comparar efectos clínicos de tiopental y propofol en la terapia electroconvulsiva, se estudiaron 50 pacientes en el Hospital Militar Central Dr Carlos J Finlay. Se empleó tiopental 3 mg/kg o propofol 1,5 mg/kg endovenoso y succinilcolina 0,5 mg/kg; se aplicó estímulo biparietal (120-150 volts). Se analizaron las variables presión arterial media, frecuencia y ritmo cardiaco, duración de la convulsión y de la recuperación. No hubo diferencias estadísticamente significativas al comparar las cifras tensionales en ambos grupos; clínicamente se presentó mayor incremento en el grupo tiopental terminada la convulsión; las arritmias cardiacas fueron más frecuentes también en este grupo (70 por ciento) al compararlo con propofol (14 por ciento). La duración de la convulsión fue 29,84 s en el grupo propofol y 37,24 s en el grupo tiopental, con tiempos de recuperación de 6,85 y 8,16 min promedio respectivamente. El propofol resultó mejor hipnótico para la terapia electroconvulsiva.

To compare clinical effects of Thyopental and Propofol in electroconvulsive therapy (ECT), 50 patients were studied in Dr Carlos J Finlay Central Military Hospital, Thyopental was used (3 mg/kg) or Propofol (1.5 mg/kg) by intravenous way, and succinylcholine ( 0.5 mg/kg) ; biparietal stimulus was applied (120-150 v). Following variables were analyzed: mean blood pressure, cardiac frequency and rhythm, duration of generalized seizure, and of recovery. There weren't significant statistically differences in comparison of tension figures in both groups; clinically there was a greater increase in Thiopental group post generalized seizure; cardiac arrhythmias were also more frequent in this group (70 percent) in comparison to Propofol (14 percent). Generalized seizure course was of 29.84 s in Propofol group, and of 37.24 in Thyopental group, with recovery times of 6.85 and 8.16 average minutes, respectively. Propofol was a better hypnotic for electroconvulsive therapy.

Assessment of the cardiovascular effects of electroconvulsive therapy in individuals older than 50 years

To evaluate the impact of electroconvulsive therapy on arterial blood pressure, heart rate, heart rate variability, and the occurrence of ischemia or arrhythmias, 38 (18 men) depressive patients free from systemic diseases, 50 to 83 years old (mean: 64.7 ± 8.6) underwent electroconvulsive therapy. All patients were studied with simultaneous 24-h ambulatory blood pressure and Holter monitoring, starting 18 h before and continuing for 3 h after electroconvulsive therapy. Blood pressure, heart rate, heart rate variability, arrhythmias, and ischemic episodes were recorded. Before each session of electroconvulsive therapy, blood pressure and heart rate were in the normal range; supraventricular ectopic beats occurred in all patients and ventricular ectopic beats in 27/38; 2 patients had non-sustained ventricular tachycardia. After shock, systolic, mean and diastolic blood pressure increased 29, 25, and 24 percent (P < 0.001), respectively, and returned to baseline values within 1 h. Maximum, mean and minimum heart rate increased 56, 52, and 49 percent (P < 0.001), respectively, followed by a significant decrease within 5 min; heart rate gradually increased again thereafter and remained elevated for 1 h. Analysis of heart rate variability showed increased sympathetic activity during shock with a decrease in both sympathetic and parasympathetic drive afterwards. No serious adverse effects occurred; electroconvulsive therapy did not trigger any malignant arrhythmias or ischemia. In middle-aged and elderly people free from systemic diseases, electroconvulsive therapy caused transitory increases in blood pressure and heart rate and a decrease in heart rate variability but these changes were not associated with serious adverse clinical events.