Estimulantes de tipo anfetamínico en estudiantes de medicina latinoamericanos: una revisión / Amphetamine-type stimulants in Latin American medicine students: a review

Introducción: el consumo de estimulantes de tipo anfetamínico (ETA) y sus derivados está cada vez más presente en los estudiantes universitarios y, en particular, en los programas de medicina. El objetivo principal de este estudio fue revisar la literatura sobre el uso de ETA y sus derivados en estudiantes de medicina latinoamericanos. Materiales y método: se realizó una revisión de la literatura disponible, utilizando las bases de datos PubMed, SciELO y LILACS. Se encontraron un total de 1.054 artículos, de los cuales 17 fueron seleccionados para esta revisión. Resultados: la revisión muestra, en general, una mayor frecuencia de uso de ETA en estudiantes de medicina de América Latina en comparación con la población general y estudiantes de otras carreras universitarias. También existe una tendencia a un mayor uso en hombres, de mayor nivel socioeconómico y en cursos posteriores del programa. La razón más informada para usar ETA fue aumentar el rendimiento académico. Como factor protector se destacaron los deportes, el tiempo en familia y la profesión de alguna creencia religiosa. De los artículos seleccionados, no se encontraron estudios sobre las consecuencias a largo plazo del uso de ETA en estudiantes de medicina. Discusión: en resumen, los estudiantes de medicina latinoamericanos tienen un alto consumo de ETA, por lo que es evidente la necesidad de nuevos estudios para mejorar la precisión estadística, determinar factores de riesgo específicos, estudiar las consecuencias a largo plazo y establecer políticas de prevención y tratamiento.

Introduction: the consumption of amphetamine-type stimulants (ATS) and their derivatives are increasingly present in university students and in particular in medical programs. The main objective of this study was to review the literature on the use of ATS and their derivatives in Latin American medical students. Materials and method: a review of the literature available was performed, using PubMed, SciELO, and LILACS databases. A total of 1054 articles were found, of which 17 were selected for this review. Results: the review generally shows a higher frequency of use of ATS in medical students of Latin America compared to the general population and students from other university degrees. There is also a tendency of a higher use in men, from higher socioeconomic status, and in later courses of the program. The most reported reason for using ATS was to increase the academic performance. As a protective factor, sports, family time and professing some religious belief stood out. Of the selected articles, no studies were found on the long-term consequences of the use of ATS in medical students. Discussion: in summary, Latin American medical students have a high consumption of ATS, and therefore there is an evident need for new studies to improve statistical precision, to determine specific risk factors, to study long-term consequences, and to stablish prevention policies and treatment.

Uso de metilfenidato en el trastorno por déficit de atención e hiperactividad / Use of methylphenidate in attention-deficit hyperactivity disorder

Resumen El Hospital Infantil de México Federico Gómez se encuentra afiliado a la Colaboración Cochrane. Como parte de las actividades del Centro Cochrane del Hospital Infantil de México Federico Gómez, se promueve el uso de las revisiones sistemáticas para la toma de decisiones en salud. Con ese objetivo, se realizará la publicación periódica de resúmenes de revisiones sistemáticas Cochrane sobre temas relevantes que apoyen la práctica clínica.

Abstract Hospital Infantil de México Federico Gómez is affiliated with the Cochrane Collaboration. As part of the activities of the Cochrane Center of the Hospital Infantil de México, the use of systematic reviews in health decision making is promoted. With this objective, summaries of Cochrane systematic reviews on relevant topics will be periodically published to support the clinical practice.

Prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among university students / Prevalência e fatores associados ao uso de metilfenidato para neuroaprimoramento farmacológico entre estudantes universitários

ABSTRACT Objective To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. Methods Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. Results Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. Conclusion The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.

RESUMO Objetivo Estimar a prevalência e os fatores associados ao uso de metilfenidato para neuroaprimoramento entre estudantes universitários. Métodos Amostra aleatória simples de discentes da Universidade Federal de Minas Gerais (n=438), convidados a responder um questionário online sobre o consumo de metilfenidato. A coleta ocorreu de setembro de 2014 a janeiro de 2015. A amostra foi descrita em termos de proporções, médias e desvio padrão. A análise multivariada foi realizada utilizando o algoritmo Classification and Regression Tree para classificação dos casos de uso do metilfenidato para neuroaprimoramento em grupos, com base nas variáveis de exposição. Resultados Dos 378 alunos incluídos, 5,8% (n=22) declararam ter feito uso de metilfenidato para neuroaprimoramento, sendo 41% (9/22) nas 4 semanas anteriores à pesquisa. A situação da moradia foi a variável mais associada ao uso de metilfenidato para neuroaprimoramento. Relataram o uso do metilfenidato para neuroaprimoramento e outros fins nas 4 semanas anteriores à pesquisa 11 estudantes, sendo que 27% não apresentaram prescrição médica para adquiri-lo. Conclusão O uso de metilfenidato para neuroaprimoramento ocorre no meio acadêmico brasileiro e deve ser considerado sério problema de saúde pública, principalmente diante dos riscos de danos e efeitos adversos associados ao seu uso.

Effects of N-acetylcysteine on amphetamine-induced sensitization in mice

Objective: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. Methods: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg. NAC (60 mg/kg) or saline was administered intraperitoneally before saline or amphetamine during the second and third weeks. After a 4-week washout period, latent inhibition (LI) and the locomotor response to amphetamine 2 mg/kg were assessed. Results: Sensitization disrupted LI and amplified the locomotor response; NAC disrupted LI in control mice. In sensitized animals, NAC attenuated the enhanced locomotion but failed to prevent LI disruption. Conclusion: NAC warrants consideration as a candidate for early intervention in ultra-high risk subjects due to its safety profile and the relevance of its mechanism of action. Supplementing this proposition, we report that NAC attenuates sensitization-induced locomotor enhancement in mice. The finding that NAC disrupted LI incites a cautionary note and requires clarification.

Consumo de modafinilo en profesionales de la salud mental: reporte de un caso y revisión bibliográfica / Modafinil use in mental health professionals: case report and bibliographic review

INTRODUCCIÓN El presente estudio busca comenzar un abordaje inicial del fenómeno del consumo de Modafinilo en profesionales de la Salud Mental en Chile y los factores precipitantes que promueven el consumo de esta sustancia psicoestimulante. OBJETIVOS: Realizar una revisión bibliográfica respecto del consumo de Psicoestimulantes en Profesionales de la Salud Mental; identificar el psicoestimulante de más fácil acceso; buscar y contactar a profesionales de la salud mental del SSMC que consuman activamente Modafinilo e Identificar los posibles factores precipitantes asociados al consumo de Modafinilo. MATERIAL Y MÉTODOS: Reporte de caso y análisis de discurso de una entrevista en profundidad, identificando las categorías centrales que estructuran la experiencia del profesional respecto de su consumo. RESULTADOS Y DISCUSIÓN: De acuerdo al análisis de la entrevista, podemos destacar cuatro factores que desencadenan el consumo habitual de la sustancia psicoestimulante: la narcolepsia, sobrecarga laboral, sobrecarga emocional y el fácil acceso al Modafinilo. CONCLUSIONES: La bibliografía existente es muy escasa; este estudio se constituye como una primera aproximación al abordaje de este tema a nivel nacional; la sobrecarga emocional cobra gran importancia ya que complementa la dependencia fisiológica; los estados emocionales que generan y mantienen el consumo en el profesional se ven asociados a eventos ambientales, y la dependencia psicológica es una realidad inseparable de la dependencia fisiológica.

BACKGROUND: The present study aims to start an initial approach to the phenomenon of Modafinil use in mental health professionals in Chile, and the precipitating factors that promote the consumption of this psychostimulant substance. OBJETIVES: To carry out a bibliographic review regarding the use of Psychostimulants in Mental Health Professionals; to identify the most easily accessible psychostimulant; to find and contact mental health professionals who actively consume Modafinil and to identify the possible precipitating factors associated with consumption of Modafinil. METHODS: Case report and discourse analysis of an in-depth interview, identifying the central categories that structure the professional's experience regarding their consumption. RESULTS AND DISCUSSION: According to the analysis of the interview, we can highlight four factors that trigger the habitual consumption of the psychostimulant substance: Narcolepsy, work overload, emotional overload and easy access to Modafinil. CONCLUSIONS: The existing literature is very scarce; this study constitutes a first approach of this topic at national level; emotional overload is of great importance since it complements the physiological dependence; the emotional states that generate and maintain consumption in the professional are seen associated with environmental factors, and psychological dependence is an inseparable reality of physiological dependence.

Attention-deficit/hyperactivity disorder: the impact of methylphenidate on working memory, inhibition capacity and mental flexibility / Transtorno do déficit de atenção/hiperatividade (TDAH): o impacto do metilfenidato na memória operacional, capacidade inibitória e flexibilidade mental

ABSTRACT Objective To compare children with attention-deficit/hyperactivity disorder (ADHD), before and after the use of methylphenidate, and a control group, using tests of working memory, inhibition capacity and mental flexibility. Methods Neuropsychological tests were administrated to 53 boys, 9–12 years old: the WISC-III digit span backward, and arithmetic; Stroop Color; and Trail Making Tests. The case group included 23 boys with ADHD, who were combined type, treatment-naive, and with normal intelligence without comorbidities. The control group (n = 30) were age and gender matched. After three months on methylphenidate, the ADHD children were retested. The control group was also retested after three months. Results Before treatment, ADHD children had lower scores than the control group on the tests (p ≤ 0.001) and after methylphenidate had fewer test errors than before (p ≤ 0.001) Conclusion Methylphenidate treatment improves the working memory, inhibitory control and mental flexibility of ADHD boys.

RESUMO Objetivo Comparar crianças com transtorno de déficit de atenção/hiperatividade (TDAH) com controles, utilizando testes de memória de trabalho, capacidade inibitória e flexibilidade mental, em meninos de 9 a 12 anos. Métodos Testes neuropsicológicos administrados: teste de ordem inversa dos dígitos, teste aritmético (WISC-III), Teste Stroop e Teste de Trilhas. Grupo experimental meninos (n=23), com TDAH combinado, virgens de tratamento, inteligência normal sem comorbidades. Grupo controle (n = 30) com as mesmas características do grupo experimental em termos de idade e sexo. Após três meses com metilfenidato, os grupos TDAH e controle foram novamente testadas. Resultados Antes do tratamento, as crianças com TDAH apresentaram menor pontuação do que o grupo controle nos testes analisados (p≤ 0.001) e o grupo com TDAH apresentou menos erros nos testes após metilfenidato (p ≤ 0.001). Conclusão O tratamento com metilfenidato melhora a memória de trabalho, controle inibitório e flexibilidade mental de meninos com TDAH.

Intake of stimulant foods is associated with development of parasomnias in children / Ingestão de alimentos estimulantes está associada ao desenvolvimento de parassonias em crianças

ABSTRACT Objective To verify if nighttime feeding habits can influence parasomnia in children. Method Seven private and four public Elementary Schools took part in the study. A total of 595 Sleep Disturbance Scale for Children were distributed to the parents of children aged from 7 to 8 years. Data of dietary recall, starting time to school, physical activity, and nutritional status were studied. Results Of the 226 questionnaires completed, 92 (41%) reported parasomnia. Girls had 2.3 times more the chance to parasomnia than boys. Children who consumed stimulant foods had 2.6 times more chance to have parasomnia than those of children who consumed non-stimulant foods. There were no difference between parasomnia and no-parasomnia groups in food type (p = 0.78) or timing of last meal before bedtime (p = 0.50). Conclusion Our findings suggest that intake of stimulant foods is associated with development of parasomnia in children.

RESUMO Objetivo Verificar se hábitos de alimentação noturna influenciam parassonias em crianças. Método Sete escolas privadas e quatro públicas, de Ensino Fundamental, fizeram parte do estudo. Um total de 595 Escalas de Distúrbio do Sono para Crianças foram distribuídas para os pais de crianças entre 7 e 8 anos. Dados de recordatório alimentar, período escolar, atividade física e estado nutricional foram estudados. Resultados Dos 226 questionários preenchidos, 92 (41%) relataram presença de parassonias. Meninas tiveram 2,3 vezes mais chance de parassonias e crianças que consumiram alimentos estimulantes tiveram 2,6 vezes mais chance de parassonias em relação àquelas que consumiram alimentos não estimulantes. Não houve diferença entre os grupos em relação ao tipo de alimento (p = 0,78) ou horário da última refeição antes de ir para a cama (p = 0,50). Conclusão Nossos achados sugerem que a ingestão de alimentos estimulantes está associada com o desenvolvimento de parassonias em crianças.

Exposure to methylphenidate during infancy and adolescence in non-human animals and sensitization to abuse of psychostimulants later in life: a systematic review / Exposição a metilfenidato na infância e adolescência em modelos não humanos e sensibilidade ao abuso de drogas psicoestimulantes na vida adulta: revisão sistemática

Introduction:Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric pathology that has an important prevalence among young people and is difficult to diagnose. It is usually treated with methylphenidate, a psychostimulant with a mechanism of action similar to that of cocaine. Previous studies show that repeated use of psychostimulants during childhood or adolescence may sensitize subjects, making them more prone to later abuse of psychostimulant drugs such as cocaine and methamphetamine.Objective: To review experimental studies in non-human models (rodents and monkeys) treated with methylphenidate during infancy or adolescence and tested for reinforcing effects on psychostimulant drugs in adulthood.Method: Systematic collection of data was performed on four databases (Web of Knowledge, PsycARTICLE, PubMed and SciELO). The initial search identified 202 articles published from 2009 to 2014, which were screened for eligibility. Seven articles met the inclusion criteria and were reviewed in this study.Results: The findings indicate that early exposure to methylphenidate has an effect on an ADHD animal model, specifically, on spontaneously hypertensive strain rats, especially those tested using the self-administration paradigm.Conclusion:Future studies should prioritize the spontaneously hypertensive rat strain - an animal model of ADHD. Experimental designs comparing different behavioral paradigms and modes of administration using this strain could lead to improved understanding of the effects of exposure to methylphenidate during childhood and adolescence.

Introdução: O transtorno de déficit de atenção e hiperatividade (TDAH) é uma patologia neuropsiquiátrica de difícil diagnóstico e de relevante prevalência entre pessoas jovens. É comumente tratada com metilfenidato, uma substância psicoestimulante com mecanismo de ação similar ao da cocaína. Estudos prévios demonstram que o uso contínuo de fármacos estimulantes na infância ou adolescência pode sensibilizar o sujeito para o subsequente abuso de drogas psicoestimulantes, como cocaína e metanfetamina.Objetivo:Revisar estudos experimentais em modelos não humanos (roedores e macacos) tratados com metilfenidato na infância ou na adolescência e testados para os efeitos reforçadores de drogas psicoestimulantes na vida adulta.Método: A coleta sistemática dos dados foi realizada em quatro bases de dados (Web of Knowledge, PsycARTICLE, PubMed e SciELO). Na busca inicial, 202 artigos publicados entre 2009 e 2014 foram triados. Destes, sete preencheram os critérios de inclusão e foram revisados neste estudo.Resultados:Os dados indicam um efeito da pré-exposição ao metilfenidato sobre o TDAH em animais adolescentes da linhagem do rato espontaneamente hipertensivo (spontaneously hypertensive strain, SHR). Esse efeito foi encontrado, sobretudo, nos estudos que utilizaram o paradigma de autoadministração.Conclusão: Estudos futuros devem priorizar a linhagem dos SHR - modelo animal do TDAH. Delineamentos que comparem diferentes paradigmas comportamentais e formas de administração utilizando essa linhagem podem prover uma melhor compreensão do efeito da exposição ao metilfenidato na infância e adolescência.

Patterns of non-medical use of methylphenidate among 5th and 6th year students in a medical school in southern Brazil / Padrões do uso não médico de metilfenidato em estudantes do 5º e do 6º ano de uma faculdade de medicina do Brasil

Objectives: To evaluate the prevalence of methylphenidate (MPH) use among 5th and 6th year medical students, to discriminate MPH use with and without medical indication, and to correlate MPH use with alcohol intake. Methods: This is a cross-sectional study in which medical students were invited to answer a questionnaire to evaluate academic and socioeconomic status, MPH use patterns, and attitudes towards neuroenhancing drugs. The Alcohol Use Disorders Identification Test (AUDIT) was used to assess alcohol intake; a score ≥ 8 suggests potentially hazardous alcohol use. Results: Fifty-two participants (34.2%) had already used MPH, of which 35 (23.02%) had used it without medical indication. The number of 6th year students who had used MPH was more than twice higher than that of their 5th year counterparts (32.89 vs. 13.15%, respectively; p = 0.004). Also, 43.6% (p = 0.031) of the users of MPH had an AUDIT score ≥ 8; 33.3% (p = 0.029) of non-medical users of MPH had an AUDIT score ≥ 8. Conclusions: In this study, the use of MPH without medical indication was prevalent. Our findings also confirmed the association between non-medical use of MPH and potentially hazardous alcohol use (AU)

Objetivos: Avaliar a prevalência do uso do metilfenidato entre estudantes do 5º e do 6º ano de uma faculdade de medicina, discriminar o uso com ou sem indicação médica e correlacionar o uso de metilfenidato com a ingestão de álcool. Métodos: Este é um estudo transversal, em que os alunos de medicina foram convidados a responder um questionário para avaliação do status socioeconômico e acadêmico, padrões do uso do metilfenidato e atitude em relação a drogas potencializadoras da cognição. Também foi aplicado o questionário The Alcohol Use Disorder Identification Test (AUDIT), que avalia o consumo de bebidas alcoólicas, onde um score ≥ 8 significa ingestão potencialmente perigosa de álcool. Resultados: Cinquenta e dois participantes (34,2%) já haviam usado metilfenidato, sendo que 35 destes (23,02%) haviam usado a substância sem indicação médica. O número de estudantes do 6º ano que fizeram uso não médico de metilfenidato foi mais de duas vezes maior do que o número de estudantes do 5º ano (32,89 versus 13,15%, respectivamente; p = 0,004). Em relação ao AUDIT, 43,6% (p = 0,031) dos usuários de metilfenidato tiveram escores ≥ 8; 33,3% (p = 0,029) dos usuários não médicos de metilfenidato tiveram escores ≥ 8 no AUDIT. Conclusões: Neste estudo, o uso de metilfenidato sem indicação médica foi prevalente. Os achados também evidenciaram a associação entre o uso não médico de metilfenidato e o uso potencialmente perigoso de álcool (AU)

Efectividad y seguridad de risperidona en terapia combinada con estabilizadores del ánimo en personas con trastorno afectivo bipolar / Effectiveness and safety of risperidone in combination therapy with mood stabilizers in people with bipolar affective disorder

Antecedentes: Descripción de la condición de salud de interés: El trastorno maníaco-depresivo (CIE-10: F31), término acuñado por Emil Kraepelin a fines del siglo XIX, es una enfermedad mental que la psiquiatría clasifica como un desorden afectivo; cuando se manifiesta se acompaña de episodios alternantes o concurrentes de manía o depresión (que pueden durar horas o días) se habla de un trastorno afectivo bipolar. El diagnóstico está basado primordialmente en las propias experiencias y vivencias del sujeto, así como anomalías del comportamiento reportadas por familiares o compañeros de trabajo, todo lo cual finalmente es caracterizado por profesionales de salud ­específicamente psiquiatras, que pueden encontrar difícil clasificar a un individuo como afectado por un trastorno monopolar o uno bipolar; el diagnóstico diferencial de la enfermedad involucra a la esquizofrenia, el desorden de hiperactividad y déficit de atención, la fobia social o la personalidad limítrofe entre otras condiciones que ­cabe anotar- pueden coexistir con el TAB. Aunque se usan escalas, tales como la de diagnóstico de espectro bipolar, éstas no reemplazan el ejercicio de una historia clínica y mental completa. Descripción de la tecnología: La risperidona es un fármaco de alta potencia antipsicótica, predominando sobre su acción sedante. Pertenece al grupo de los antipsicóticos nuevos o atípicos, los cuales tienen un mejor perfil de seguridad, al presentar una menor incidencia de efectos extrapiramidales. Risperidona está indicado en el tratamiento de las psicosis esquizofrénicas agudas y crónicas. También alivia los síntomas afectivos (tales como depresión, sentimientos de culpabilidad, ansiedad) asociados a la esquizofrenia. Evaluación de efectividad y seguridad: Pregunta de investigación: En pacientes adultos con trastorno afectivo bipolar ¿cuál es la efectividad y seguridad de risperidona, olanzapina, quetiapina o aripripazol (antipsicóticos) en combinación con litio o divalproato sódico (estabilizadores del estado de ánimo) comparados con monoterapia de litio o divalproato sódico (estabilizadores del ánimo) para disminuir la recurrencia de la alteración del estado de ánimo (episodios maníacos, depresivos o episodios afectivos mixtos), incidencia de eventos adversos y retiro del tratamiento? La pregunta de investigación fue refinada y validada con base en: autorización de mercadeo de la tecnología para la indicación de interés (registro sanitario INVIMA), listado de medicamentos vitales no disponibles, cobertura de las tecnologías en el Plan Obligatorio de Salud (POS) (Acuerdo 029 de 2011), revisión de grupos terapéuticos (código ATC: Anatomical, Therapeutic, Chemical classification system), recomendaciones de guías de práctica clínica actualizadas, disponibilidad de evidencia sobre efectividad y seguridad, uso de las tecnologías (listas nacionales de recobro, estadísticas de prescripción, entre otros), estudios de prevalencia/incidencia y carga de enfermedad y consulta con expertos temáticos (especialistas clínicos), sociedades científicas y otros actores clave. Población: Estudios cuya población objeto son adultos con diagnóstico de trastorno afectivo bipolar. Metodología: Búsqueda de literatura, Búsqueda en bases de datos electrónicas. Conclusiones: Efectividad: la combinación de risperidona, olanzapina, quetiapina o aripripazol con litio o divalproato sódico (estabilizadores del ánimo) como terapia de mantenimiento para el trastorno afectivo bipolar es más efectiva en comparación con monoterapia de litio o divalproato sódico, para los desenlaces de episodios de recaída de alteración del ánimo (episodios maniacos, depresivos o mixtos). No es significativa la diferencia en efectividad entre los antipsicóticos (risperidona, olanzapina, quetiapina, aripripazol) para los episodios de alteración del ánimo (episodios maniacos, depresivos o mixtos). Aunque la adición de psicoterapia al manejo del TAB excede el objetivo de esta evaluación, hay información proveniente de la evidencia aquí incluída que señala como la estrategia más efectiva, la adición de psicoterapia a la terapia farmacológica para el tratamiento del TAB.\r\nSeguridad: los antipsicóticos se asocian con mayor frecuencia de eventos adversos en comparación con placebo; no hay evidencia conclusiva sobre las diferencias de efectos adversos entre los antipsicóticos (risperidona, olanzapina, quetiapina, aripripazol). No se encontró evidencia para el desenlace retiro de tratamiento en la terapia combinada de mantenimiento.

Evaluación de la efectividad y seguridad del metilfenidato de acción larga versus acción corta en el déficit atencional en población entre 6 y 19 años: revisión sistemática / Effectiveness and safety of long-acting versus short acting methylphenidate in ADHD in population between 6 and 19 years: a systematic review

Introducción: el trastorno por déficit de atención e hiperactividad (TDAH) dispone como tratamiento farmacológico el metilfenidato de acción corta, pero recientemente ha surgido una presentación de acción larga; de aquí el interés del estudio para evaluar las dos formulaciones. Objetivo: identificar, sintetizar y evaluar la mejor evidencia disponible sobre la efectividad y seguridad del metifenidato de acción larga vs acción corta para el tratamiento en déficit atencional en la población de 6 a 19 años. Métodos: revisión sistemática de estudios de intervenciones comparando las dos presentaciones de metilfenidato; se midió efectividad en términos de funcionamiento educacional, funcionamiento psicosocial, calidad de vida y efectos adversos. Se consultaron bases de datos hasta febrero de 2012 en inglés y castellano: PubMed, Lilacs, Cochrane, DARE y Guideline. Se evaluó por dos investigadores en forma independiente. Resultados: de los 18 estudios encontrados inicialmente, se incluyeron 6, entre ellos una revisión sistemática, un artículo primario de intervenciones terapéuticas y 4 guías clínicas. Conclusiones: el metilfenidato de larga acción no resulta ser superior al metilfenidato de corta acción en términos de funcionamiento educacional, funcionamiento psicosocial, calidad de vida, con pocos efectos adversos, en el tratamiento de pacientes entre 6 y 19 años de edad con déficit atencional.

Introduction: Attention deficit hyperactivity disorder (ADHD) is generally treated with short-acting methylphenidate, but recently a long-acting presentation has been introduced, hence the interest of the study to evaluate the two formulations. Purpse: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of long-acting methylphenidate versus short-acting treatment for ADHD in the 6-19 year-old population. Methods: A systematic review of intervention studies comparing the two presentations of methylphenidate was conducted. Effectiveness was measured in terms of educational performance, psychosocial functioning, quality of life and adverse effects. Databases were searched until February 2012 in English and Spanish: PubMed/MEDLINE, Lilacs, Cochrane, DARE and National Guideline Clearinghouse. The studies were evaluated by two investigators independently. Results: Of the 18 studies found initially, six were included, among which a systematic review, a primary article on therapeutic interventions and four clinical guidelines. Conclusions: Long-acting methylphenidate is not superior to short-acting methylphenidate in terms of educational performance, psychosocial functioning, quality of life. Few adverse effects were found in the treatment of patients between 6 and 19 years old with attention deficit disorder.

Zinc en la terapia del síndrome de déficit de atención e hiperactividad en niños: Un estudio controlado aleatorio preliminar / Zinc in the therapy of the attention-deficit/ hyperactivity disorder in children: A preliminar randomized controlled trial

El síndrome de déficit de atención e hiperactividad (ADHD) es un trastorno neurológico /conductual que se inicia en la infancia. Se ha propuesto que el zinc tendría un potencial rol como terapia adjunta para el ADHD. Nuestro objetivo fue evaluar el efecto de la suplementación con zinc sobre la conducta, como terapia complementaria al metilfenidato, en niños con ADHD. En un estudio controlado, doble ciego, se seleccionaron 40 pacientes con criterios clínicos y psicométricos de ADHD, (31 niños, 9 niñas, 7-14 años de edad). Ellos fueron seleccionados aleatoriamente para recibir ya sea metilfenidato 0,3 mg/kg/d + placebo (sacarosa) (grupo placebo, GPL), o metilfenidato 0,3 mg/kg/d + zinc (sulfato) 10 mg/d (grupo Zn, GZN) por 6 semanas; se excluyeron 4 niños. Se tomó una muestra de 3 mL de sangre en el tiempo 0 y a las 6 semanas para el análisis de Zn plasmático; se aplicó en ambos tiempos a padres y profesores la escala abreviada de Conners para ADHD. Entre los resultados, El Zn plasmático fue normal en el tiempo 0 en ambos grupos, disminuyendo después de 6 sem., especialmente en el grupo GPL (GPL: 95,9 ± 21,5 a 77,9 ± 15,5; GZN: 90.3 ± 9.1 a 85,0 ± 12,0 μg/dl, NS). El test de Conners aplicado por los profesores mostró una aparente mejoría en GZN: GPL: 18 (9-28) a 16 puntos (2-26); GZN: 19 (6-24) a 11 puntos (3-23) (p= 0,07), sin mejoría en el Conners aplicado por los padres: GPL: 19 (7-25) a 13 (3-22); GZN: 19 (7-25) a 11 (2-19). Se concluye que se observa una disminución en las concentraciones plasmáticas de Zn en ambos grupos, pero mayor en el grupo placebo. Con el suplemento de zinc se observa una aparente mejoría en los síntomas de ADHD, de acuerdo con la evaluación de Conners aplicada por profesores. Se requiere avanzar en el estudio de esta probable interacción entre zinc y metilfenidato.

The attention-deficit/hyperactivity disorder (ADHD) is a neurological/behavioral disorder which begins in childhood. Zinc has a potential role as an adjuvant therapy for ADHD. The objective was to evaluate the effect of Zn supplementation on behavior, as a complementary therapy to metylphenidate, in pediatrics patients with ADHD. In a controlled, double blind design, 40 patients with clinical criteria of ADHD (DSMIV) and psychometric evaluation (WISC-R), were selected (31 boys and 9 girls, 7-14 years of age). They were randomized to receive methylphenidate 0.3 mg/kg/d + placebo (sucrose) (group placebo, GPL) or methylphenidate 0.3 mg/kg/d + zinc (sulfate) 10 mg/d (group Zn, GZN) for 6 weeks. A blood sample was drawn at time 0 and 6 weeks, for plasma Zn analysis. The teacher and parent ADHD rating scale (Conners` global index, CGI) was applied at both times. Among the results, plasma Zn was normal at time 0, decreasing especially in the GPL after 6 weeks (GPL: 95.9 ± 21.5 to 77.9 ± 15.5; GZN: 90.3 ± 9.1 to 85.0± 12.0 μg/dL; NS). The CGI by teachers showed a non-significant improvement with Zn: GPL: 18 (9- 28) to 16 points (2-26); GZN: 19 (6-24) to 11 points (3-23) (p=0.07); no significant difference in the CGI by parents by groups was found: GPL: 19 (7-25) to 13 (3- 22); GZN: 19(7-25) to 11(2-19). We conclude that a decrease in plasma Zn levels in both groups was found, greater in the placebo group. An apparent improvement in ADHD signs in children was observed with the Zn supplementation, according to the Conners global index by teachers.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

La observación de la autoregulación de la atención visual y de la variabilidad mímica como método para la determinación de la dosis de metilfenidato en niños con TDAH / Observation of the autoregulation of the visual attention and facial expression of emotions variability like method for the determination the dose of methylphenidate in ADHD children

Los niños con Trastorno por Déficit de Atención/Hiperactividad (TDAH) según estudios previos, muestran significativamente más interrupciones del foco visual e invariabilidad de la expresión facial de emociones. En un grupo clínico de 25 niños con TDAH de una edad promedio de 10 años y cuatro meses, examinamos en qué forma este estado de desregulación fue modificado a través de administración de metilfenidato (MF), aumentando las dosis en pequeñas etapas de 2,5 mg por dosis. Grabaciones de un juego de naipes con la madre con dosis diferentes fueron revisadas por cuatro observadores, quienes no conocían ni a los pacientes ni las dosis. Se cuantificaron las interrupciones del foco visual y se determinó la variabilidad de la sonrisa en una escala de 5 puntos. Se observó una relación en forma de U entre dosis de MF y atención visual. La variabilidad mímica y los resultados correctos de ejercicios matemáticos que además debían ejecutar, mostraron una función U inversa. La mejor regulación coincidió con el mejor rendimiento. Los niños tratados con dosis de MF determinadas por este método mostraron resultados clínicos buenos y un mejoramiento altamente significativo de los síntomas del TDAH según DSM-IV en escalas de evaluación de los padres. El método puede ser aplicado en la consulta del pediatra, psiquiatra o neurólogo.

According to previous reports, the children with Attention-deficit hyperactivity disorder (ADHD) show significantly more interruptions at the visual focus and invariability of emotional facial expression. In a clinical group of 25 children with ADHD with an average age of 10 years and tour months, we examine in which way this state of deregulation was modified through the administration of methylphenidate (MF), increasing the doses in short steps of 2,5 mg per dose. Recordings of a card game with their mother with different doses were checked by four observers, who were blind to dose status and hadn’t previously met the patients. We quantified the visual focus interruptions and the smile variability with a five-point scale. We observed a U-shaped relationship between the MF dose and visual attention. The facial expression variability and the correct execution of mathematical exercises, showed an inverse U-shaped function. The best regulation was related with a better achievement. The children treated with doses of MF, determined by this method showed good clinical results and improvement of the ADHD symptoms in the scales at evaluation at the parents. This method can be used in the neurologist’s, psychiatrist’s or pediatrician’s office.

Hepatitis C among former athletes: association with the use of injectable stimulants in the past

This study was performed with the purpose of testing the hypothesis that the high prevalence of hepatitis C among former athletes is associated with their past use of injectable stimulants. The study involved the participation of 208 former professional and amateur soccer and basketball players from the region of Ribeirão Preto, Brazil, who answered a questionnaire regarding their exposure to risk factors, including the use of injectable stimulants in the time they were engaged in sporting activities. ELISA tests were used to detect infection by the hepatitis C virus, and confirmed with PCR and genotyping for the positive cases. It was observed that the former use of injectable stimulants was a practice disseminated among the participants (24.5 percent), reaching 50.8 percent in the professionals. The overall prevalence for hepatitis C was 7.2 percent, with values of 11 percent among professionals and 5.5 percent among amateurs. In both categories, the presence of infection was markedly higher among those who admitted past use of injectable stimulants when compared to those who denied such practice (36 percent and 0.8 percent among amateurs; 21.9 percent and 0 percent among professionals, respectively). Multivariate analysis showed that the use of those substances was the only variable associated with the risk of hepatitis C. This confirms previous observations, performed with reduced sample sizes and without comparison groups, which indicated that the use of injectable vitamins was a risk factor of hepatitis C among former athletes.

Effects of Methylphenidate on Quantitative EEG of Boys with Attention-deficit Hyperactivity Disorder in Continuous Performance Test

The purpose of this study was to investigate the effects of methylphenidate, a psychostimulant, on quantitative electroencephalography (QEEG) during the continuous performance test (CPT) in boys with attention-deficit hyperactivity disorder (ADHD). The QEEG was obtained from 20 boys with ADHD. The amplitudes of 4 bands (alpha, beta, delta, and theta) in the QEEG, as well as the theta/beta ratio, before and after the administration of methylphenidate were compared during both the resting and CPT states. Methylphenidate induced a significant increase of alpha activities in both the right and left frontal and occipital areas, an increase of beta activities in almost all areas except for the temporal region, a decrease of theta activities in both the occipital and right temporo-parietal areas, a mild decrease of delta activities in the occipito-parietal areas, and an increase of the theta/beta ratio in the right frontal and parieto-occipital, and left temporal areas during the CPT state. No significant QEEG changes were induced by the administration of methylphenidate in the resting state. These data suggest that methylphenidate has greater electrophysiological influences on the cerebral topographical activities during the performance of attentional tasks, as compared to the resting state, in boys with ADHD.

Chronic administration of caffeine: effect on the activities of hepatic antioxidant enzymes of Ehrlich ascites tumor-bearing mice.

Chronic ingestion (for 22-30 consecutive days) of caffeine (20 mg/kg/day, p.o.) increased the activities of the hepatic enzymes- catalase (CAT) and superoxide dismutase (SOD) and decreased its lipid peroxidation (LP) in mice. Development of Ehrlich ascites carcinoma (EAC) cell decreased the activities of hepatic CAT and SOD and increased LP. But pretreatment of caffeine for 12 consecutive days and continuation of its treatment during the course of development of EAC cells restored the EAC cell-induced changes in liver CAT, SOD and LP to their corresponding control values. Thus, the present results by confirming the results of others previously published, suggest that caffeine is an antioxidant and may act as an anticarcinogen.

Avaliação clínica da eficácia da combinação paracetamol e cafeína no tratamento da cefaléia tipo tensão / Clinical evaluation of the efficacy of the paracetamol and caffeine combination in the treatment of tension headache

A cefaléia tipo tensão em suas duas modalidades, episódica e crônica, é a forma mais comum de dor de cabeça na população. O tratamento é feito com medidas não farmacológicas e farmacológicas, tanto para o ataque como profilaxia das crises. Este estudo foi realizado com 5490 pacientes, que procuraram ambulatórios e consultórios médicos em várias regiões do Brasil. Cerca de 95 por cento apresentavam cefaléia tipo tensão episódica e 5 por cento cefaléia tipo tensão crônica. A maioria dos pacientes apresentou crises de intensidade moderada (62,19 por cento). Em 5419 pacientes uma crise de cefaléia tipo tensão foi tratada com 1000 mg de paracetamol e 130 mg de cafeína. Em 93,98 por cento início de melhora foi observado em até 2 horas após a ingestão da medicação. Em 77,61 por cento houve reversão completa da crise em até 2 horas. Avaliação da eficácia boa/excelente foi observada em 51,93 por cento/37,80 por cento dos casos quando feita pelos médicos e em 48,51 por cento/40,29 quando pelos pacientes. Efeitos adversos, em geral manifestações gastrointestinais, foram observados em 5,57 por cento. Este estudo representa uma experiência brasileira no tratamento de ataque da cefaléia tipo tensão, demonstrando eficácia e segurança no uso da combinação paracetamol-cafeína.

Pautas para uso de psicofármacos / Use standards of psychotropic drugs

Algunos trastornos del desarrollo, emocionales y conductuales de niños y adolescentes pueden ser tratados con psicofármacos, pero un cambio satisfactorio y estable sólo es posible lograr si se manejan simultáneamente otras variables que los determinan: personales, ambientales y familiares. Existe en la práctica médica una cierta tendencia a la indicación de psicofármacos sin un diagnóstico consistente y obviando los riesgos inherentes al uso de éstos. Es así como se trata, a veces innecesariamente, patología banal y variaciones normales del desarrollo. Se reseña a continuación algunos elementos básicos de psicofarmacoterapia clínica, a considerar en aquellas ocasiones que se opte por la indicación luego de un cuidadoso análisis clínico

Effect of apomorphine on rat motor activity induced by fencamfamine and other indirect psychostimulant drugs

We evaluated the effects of low doses of apomorphine on the stimulant behavioral effects induced by amphetamine (2.5 mg/Kg), fencamfamine (6.0 mg/Kg) and cocaine (15,0 mg/Kg). Rats received 0.02 mg/Kg of apomorphine (sc) and 30 min later were injected with one of the stimulants.Motor activity including locomotion, rearing and sniffing was quantified in the animals home cages for 60 min at 15-min intervals. All stimulant drugs induced hyperactivity. When apomorphine was administered before cocaine, but not when administered before fencmfamine or amphetamine, distinctive changes occurred. The behavioral pattern resulting from high stimulation was replaced by that related to low stimulation, suggesting that apomorphine induces a transfer in the predominant behvior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occured when apomorphine was administered before amphetamine, the fencamfamine group showed intermediate alterations (nonsignificant changes in sniffing but a significant increase in rearing behavior). These results are discussed in terms of the different mechanisms of presynaptic action of the drugs studied