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.

Actualización en abuso de drogas por vía nasal / Update on drug abuse by nasal route

La vía nasal, ya sea mediante la inhalación o aspiración, se ha convertido en una ruta atractiva para quienes abusan de sustancias, principalmente por la fácil accesibilidad y la rápida absorción sistémica, además de evitar las consecuencias asociadas al uso de drogas intravenosas (enfermedades de transmisión). El objetivo de esta revisión es presentar una actualización de diversas sustancias que son utilizadas por esta vía, enfocándose en aquellas en las que se ha documentado daños en la anatomía nasal.

The nasal route, either by inhalation or aspiration, has become an attractive route for substances abusers, mainly because of its easy accessibility, rapid systemic absorption and also to avoid the consequences associated with intravenous drug use (transmitted diseases). The objective of this review is to present an update of various substances that are used by this route, focusing on those in which damage to the nasal anatomy has been documented.

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.

Auditory Processing Assessment in Children with Attention Deficit Hyperactivity Disorder: An Open Study Examining Methylphenidate Effects

Abstract Introduction Children with Attention Deficit Hyperactivity Disorder can present Auditory Processing (AP) Disorder. Objective The study examined the AP in ADHD children compared with non-ADHD children, and before and after 3 and 6 months of methylphenidate (MPH) treatment in ADHD children. Methods Drug-naive children diagnosed with ADHD combined subtype aging between 7 and 11 years, coming from public and private outpatient service or public and private school, and age-gender-matched non-ADHD children, participated in an open, non-randomized study from February 2013 to December 2013. They were submitted to a behavioral battery of AP tests comprising Speech with white Noise, Dichotic Digits (DD), and Pitch Pattern Sequence (PPS) and were compared with non-ADHD children. They were followed for 3 and 6 months of MPH treatment (0.5 mg/kg/day). Results ADHD children presented larger number of errors in DD (p < 0.01), and less correct responses in the PPS (p < 0.0001) and in the SN (p < 0.05) tests when compared with non-ADHD children. The treatment with MPH, especially along 6 months, significantly decreased the mean errors in the DD (p < 0.01) and increased the correct response in the PPS (p < 0.001) and SN (p < 0.01) tests when compared with the performance before MPH treatment. Conclusions ADHD children show inefficient AP in selected behavioral auditory battery suggesting impaired in auditory closure, binaural integration, and temporal ordering. Treatment with MPH gradually improved these deficiencies and completely reversed them by reaching a performance similar to non-ADHD children at 6 months of treatment.

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.

Prescription, dispensation and marketing patterns of methylphenidate / Padrões de prescrição, dispensação e comercialização de metilfenidato

OBJECTIVE To analyze the patterns and legal requirements of methylphenidate consumption. METHODS We conducted a cross-sectional study of the data from prescription notification forms and balance lists of drugs sales – psychoactive and others – subject to special control in the fifth largest city of Brazil, in 2006. We determined the defined and prescribed daily doses, the average prescription and dispensation periods, and the regional sales distribution in the municipality. In addition, we estimated the costs of drug acquisition and analyzed the individual drug consumption profile using the Lorenz curve. RESULTS The balance lists data covered all notified sales of the drug while data from prescription notification forms covered 50.6% of the pharmacies that sold it, including those with the highest sales volumes. Total methylphenidate consumption was 0.37 DDD/1,000 inhabitants/day. Sales were concentrated in more developed areas, and regular-release tablets were the most commonly prescribed pharmaceutical formulation. In some regions of the city, approximately 20.0% of the prescriptions and dispensation exceeded 30 mg/day and 30 days of treatment. CONCLUSIONS Methylphenidate was widely consumed in the municipality and mainly in the most developed areas. Of note, the consumption of formulations with the higher abuse risk was the most predominant. Both its prescription and dispensation contrasted with current pharmacotherapeutic recommendations and legal requirements. Therefore, the commercialization of methylphenidate should be monitored more closely, and its use in the treatment of behavioral changes of psychological disorders needs to be discussed in detail, in line with the concepts of the quality use of medicines. .

OBJETIVO Analisar padrões e requisitos legais do consumo de metilfenidato. MÉTODOS Estudo transversal realizado em Belo Horizonte, MG, em 2006. Foram analisados dados de notificações de receitas de metilfenidato e de balanços de vendas de medicamentos – psicoativos e outros – sujeitos a controle especial. Determinou-se a dose diária definida, a dose diária prescrita, o período médio de prescrição e de dispensação, bem como a distribuição regional das vendas desse medicamento no município. Foram estimados, ainda, os gastos com a aquisição do medicamento e analisado o perfil de consumo individual do fármaco por meio da Curva de Lorenz. RESULTADOS Os dados dos balanços mensais de comercialização de psicotrópicos cobriram toda a comercialização notificada do fármaco, enquanto aqueles coletados nas notificações de receita cobriram 50,6% das farmácias que o comercializaram, incluindo aquelas de maior volume de venda. O consumo de metilfenidato foi 0,37 DDD/1.000 habitantes/dia. As vendas concentraram-se em áreas mais desenvolvidas e as formulações farmacêuticas de liberação não controlada foram as mais prescritas. A prescrição e a dispensação com dosagens > 30 mg/dia e período de tratamento > 30 dias apresentaram valores em torno de 20,0% em algumas regiões da cidade. CONCLUSÕES O consumo de metilfenidato apresentou-se elevado no município, maior em áreas mais favorecidas economicamente e predominando o consumo de formulações com maior risco de abuso. Tanto a prescrição quanto a dispensação apresentaram características não compatíveis com as recomendações farmacoterapêuticas e determinações legais. O controle de venda do fármaco ...

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)

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.

Food intake and serum levels of iron in children and adolescents with attention-deficit/hyperactivity disorder / Ingestão alimentar e níveis séricos de ferro em crianças e adolescentes com transtorno de déficit de atenção/hiperatividade

Objective: To investigate hematologic variables related to iron deficiency and food intake in attention-deficit/hyperactivity disorder. Method: The sample comprised 62 children and adolescents (6-15 years old) divided into three groups: Group 1: 19 (30.6 percent) patients with attention-deficit/hyperactivity disorder using methylphenidate for 3 months; Group 2: 22 (35.5 percent) patients with attention-deficit/hyperactivity disorder who were methylphenidate naïve and Group 3: 21 (33.9 percent) patients without attention-deficit/hyperactivity disorder. Serum iron, ferritin, transferrin, hemoglobin, mean corpuscular volume, red cell distribution width, mean corpuscular hemoglobin concentration, nutritional diagnostic parameters - Body Mass Index Coefficient, food surveys were evaluated among the groups. Results: The attention-deficit/hyperactivity disorder group drug naïve for methylphenidate presented the highest red cell distribution width among the three groups (p = 0.03). For all other hematologic and food survey variables, no significant differences were found among the groups. No significant correlation between dimensional measures of attention-deficit/hyperactivity disorder symptoms and ferritin levels was found in any of the three groups. Conclusion: Peripheral markers of iron status and food intake of iron do not seem to be modified in children with attention-deficit/hyperactivity disorder, but further studies assessing brain iron levels are needed to fully understand the role of iron in attention-deficit/hyperactivity disorder pathophysiology.

Objetivo: Investigar as variáveis hematológicas relacionadas à deficiência de ferro e à ingestão alimentar no transtorno de déficit de atenção/hiperatividade. Método: Sessenta e duas crianças e adolescentes (6-15 anos) divididos em três grupos: Grupo 1: 19 (30,6 por cento) pacientes com transtorno de déficit de atenção/hiperatividade com uso de metilfenidato durante três meses; Grupo 2: 22 (35,5 por cento) pacientes com transtorno de déficit de atenção/hiperatividade sem uso de medicamento; e Grupo 3: 21 (33,9 por cento) pacientes sem transtorno de déficit de atenção/hiperatividade. Ferro sérico, ferritina, transferrina, hemoglobina, volume corpuscular médio, amplitude de distribuição dos eritrócitos, concentração da hemoglobina corpuscular média, parâmetros de diagnóstico nutricional - Coeficiente de Índice de Massa Corporal, inquérito alimentar e a correlação entre os sintomas do transtorno e os níveis de ferritina foram avaliados. Resultados: O grupo com transtorno de déficit de atenção/hiperatividade não medicado com metilfenidato apresentou maior amplitude de distribuição dos eritrócitos dentre os três grupos (p = 0,03). Nas outras variáveis hematológicas e inquéritos alimentares não encontramos diferença significativa entre os grupos. Não observamos correlação entre os sintomas do transtorno de déficit de atenção/hiperatividade e ferritina. Conclusão: Marcadores periféricos do estado nutricional de ferro e a ingestão alimentar de ferro não parecem estar modificados em crianças com transtorno de déficit de atenção/hiperatividade, mas mais estudos avaliando os níveis de ferro no cérebro são necessários para compreensão plena do papel do ferro na fisiopatologia do transtorno de déficit de atenção/hiperatividade.

Possíveis interfaces entre TDAH e epilepsia / Possible interfaces between attention deficit hyperactivity disorder and epilepsy

OBJETIVO: Identificar na literatura elementos para explicar uma possível associação entre o transtorno de déficit de atenção e hiperatividade (TDAH) e a epilepsia e orientar quanto ao manejo clínico dos pacientes que compartilham esses transtornos. MÉTODOS: Realizou-se revisão da literatura dos últimos 10 anos nas bases de dados MedLine e Lilacs com a combinação dos descritores "attention deficit hyperactivity disorder", "ADHD" e "epilepsy". RESULTADOS: Sintomas de TDAH são frequentes em síndromes epilépticas idiopáticas. Vários fatores podem contribuir para a coexistência desses transtornos: 1) possibilidade de uma mesma propensão genética; 2) participação dos neurotransmissores noradrenalina e dopamina no TDAH e na modulação da excitabilidade neuronal; 3) anormalidades estruturais do cérebro evidenciadas em epilépticos portadores de TDAH; 4) influência dos efeitos crônicos das crises e das descargas epileptiformes interictais sob a atenção; 5) efeitos adversos das drogas antiepilépticas sob a cognição. CONCLUSÕES: As evidências atuais apontam que crises epilépticas e TDAH podem apresentar bases neurobiológicas comuns. Estudos que avaliam disfunções nas vias de sinalização das catecolaminas cerebrais e o papel das descargas epileptiformes interictais na geração dos sintomas são fundamentais na investigação desses mecanismos. Drogas psicoestimulantes são seguras e eficazes para o tratamento do TDAH na maioria dos portadores de epilepsia.

OBJECTIVE: To investigate in the literature elements that explain the association between the attention deficit hyperactivity disorder (ADHD) and epilepsy and to provide clinical guidelines for the management of patients that share these disorders. METHODS:Review of literature of the last 10 years in MedLine and Lilacs databases. The keywords used were "attention deficit hyperactivity disorder", "ADHD" and "epilepsy. RESULTS: Symptoms of ADHD are more frequent in idiopathic epilepsies. Several factors may contribute to this comorbidity: 1) common genetic environment; 2) participation of neurotransmitters norepinephrine and dopamine in ADHD and in neuronal excitability modulation; 3) the underlying brain structural abnormalities found in epileptic patients with ADHD; 4)the chronic effects of seizures and of the epileptiform interictal EEG discharges in attention; 5) the cognitive side effects of antiepileptic drugs. CONCLUSIONS: Recents evidences suggest that seizures and ADHD may have common neurobiological bases. Researches that investigate dysfunctions in cerebral cathecholamines pathways and the role of the interictal epileptiform discharges in the generation of the sintoms are essencial to understand these mechanisms. Treatment for ADHD with stimulant drugs are safe and effective in most epileptic patients.

Características das prescrições no transtorno de déficit de atenção/hiperatividade / Medical prescriptions characteristics in attention deficit/hyperactivity disorder

OBJETIVO: O trabalho busca conhecer, no atual momento, a realidade das prescrições para o transtorno de déficit de atenção/hiperatividade. MÉTODO: Revisão não sistemática dos descritores "transtorno de falta de atenção/ hiperatividade" e "prescrição de medicamentos" e seus similares em inglês. Foram utilizados os seguintes limitadores: publicações de 10 anos até novembro de 2008, idiomas inglês, francês, espanhol e português, nas bases de dados do Medline, SciELO, Lilacs, áreas especializadas e Cochrane. Não foram utilizados os artigos referentes ao uso ilícito e aspectos clínicos em geral. RESULTADOS: Foram tratados 8 itens: sistema de prescrições, características socioculturais, os sistemas de saúde que influenciam as prescrições, tempo de uso das medicações, aumento das prescrições, aspectos em comum, dosagens e prescrição em idades abaixo de 5 anos. CONCLUSÕES: Alguns aspectos são preocupantes, como a baixa adesão aos tratamentos medicamentosos, doses médias de metilfenidato relativamente baixas e aumento das prescrições de psicoestimulantes para crianças de até 3 anos. Características sociais e o sistema de saúde utilizado pelo afetado também geram grandes variações na prática clínica. Uma questão interessante é a evidência de que o sistema brasileiro de prescrições não é o mais restritivo.

OBJECTIVE: The paper seeks to know the reality of the prescriptions for the attention deficit/ hyperactivity disorder. METHOD: Non-systematic review of the descriptors "attention deficit / hyperactivity disorder" and "medication prescriptions", in Portuguese and in English similar. The limiters were: 10 years publishings until November 2008, English, French, Spanish and Portuguese languages, in Medline, SciELO, Lilacs, Specialized Areas and Cochrane data base. The articles concerning the drug illicit use and clinical aspects have not been used. RESULTS: Eight items were dealt with: prescriptions system, socio-cultural characteristics and health systems that have influence on the prescriptions, medication use span, increasing prescriptions, common aspects, dosage and prescription to below 5 years old children. CONCLUSIONS: Some aspects are worrying, such as the low adhesion to the medical treatments, relatively low average doses and psychostimulants increasing prescriptions even for children up to 3 years old. Social characteristics and the health system used by the affected ones give origin to great variations on the clinical practice. An interesting issue is the evidence that the Brazilian prescriptions system isn't the most restrictive one.

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.

Dose-dependent ultrastructural changes in rat cornea after oral methylphenidate administration

To investigate dose-dependent ultrastructural changes in rat cornea after oral methylphenidate [Ritalin] administration. This study was conducted in the Department of Anatomy, Gazi University Faculty of Medicine, Ankara, Turkey between March and May 2005, with a total of 27 female prepubertal Wistar albino rats, divided into 3 different dose groups [5mg/kg, 10 mg/ kg, 20 mg/kg], and their control groups. They were treated orally with methylphenidate, and eye tissue was removed to process for electron microscopic studies. We observed that all cells, and prominently basal cells of the corneal epithelium show dose-dependent degenerative changes such as apoptotic bodies, chromatin condensation, and ondulation in their nuclei and crystolysis of the mitochondrion. In the stroma, the most evident finding was the increase of the collagen fiber. In addition to dose-dependent changes related to the apoptotic process, which is chromatin condensation in their nuclei, electron dense material accumulation, and pericellular edema in the cytoplasm were also seen. In the endothelial cell lines, disruption of the junctional complexes, vacuolization in the cell cytoplasms, and crystolysis of the mitochondrion's with rough endoplasmic reticulum cisternae activity were observed. Ritalin is inducing an evident degeneration, especially in epithelium cells with increasing doses. Ultrastructural cell organelle composition degeneration with stromal fibrosis has a negative effect on cornea dehydration. In light of these findings, we believe that the Ritalin treatment doses need to be kept to a minimum to maintain healthy cornea ultrastructure and related physiology

Questões atuais no tratamento farmacológico do TDAH em adultos com metilfenidato / Actual issues in the pharmacological treatment of ADHD in adults with methylphenidate

O tratamento farmacológico do transtorno do déficit de atenção com hiperatividade (TDAH) em adultos inclui o uso de psicoestimulantes, antidepressivos e atomoxetina, sendo o primeiro considerado a indicação de primeira escolha. A eficácia do metilfenidato foi demonstrada em adultos quando se empregavam doses maiores, proporcionalmente similares àquelas usadas em estudos em crianças. O perfil de eventos adversos do metilfenidato, incluindo aqueles relativos ao sistema cardiovascular, parece bastante seguro.

Pharmacotherapy of attention-deficit/hyperactivity disorder in adulthood includes psychostimulants, antidepressants and atomoxetine, the first of them being considered the first choice. Methylphenidate efficacy has been demonstrated in adults when higher doses were used, in a proportionate similar way to what has been described in children. Methylphenidate profile of adverse events, including cardiovascular ones, seems to be safe.

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.