Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of ADHD in males and females. However, a majority of previous studies investigated the effect of MPH in only males, and little is known regarding consequences of female exposure to MPH. This is unfortunate because the few studies that have been conducted indicate that females have a greater sensitivity to MPH. Previous research in male mice has shown that chronic exposure to MPH causes dopaminergic neurons within the nigrostriatal pathway to be more sensitive to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, estrogen has been shown to protect dopaminergic neurons from MPTP neurotoxicity. Therefore, in this study, we test the hypothesis that chronic MPH exposure in female mice will render dopaminergic neurons in the nigrostriatal pathway more sensitive to MPTP, and that estrogen may play a protective role. Interestingly, proestrus females exhibited greater sensitivity to MPTP, with significantly reduced dopaminergic neurons in the SN and significant increases in DA quinone production. Chronic MPH exposure contributed to GSH depletion, but surprisingly, it did not increase dopamine quinone levels or dopaminergic cell loss. There were no significant differences in anestrus animals, with the exception of a depletion in GSH seen when animals received chronic high-dose (10 mg/kg) MPH followed by MPTP. Thus, estrogen may actually sensitize neurons to MPTP in this model, and chronic MPH may contribute to GSH depletion within the striatum. This study provides insight into how chronic psychostimulant use may affect males and females differently.

Background: Methylphenidate (Ritalin®) is a psychostimulant used chronically to treat attention deficit hyperactivity disorder. Methylphenidate acts by preventing the reuptake of dopamine and norepinephrine, resulting in an increase in these neurotransmitters in the synaptic cleft. Excess dopamine can be autoxidized to a quinone that may lead to oxidative stress. The antioxidant, glutathione helps to protect the cell against quinones via conjugation reactions; however, depletion of glutathione may result from excess quinone formation. Chronic exposure to methylphenidate appears to sensitize dopaminergic neurons to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We hypothesized that oxidative stress caused by the autooxidation of the excess dopamine renders dopaminergic neurons within the nigrostriatal pathway to be more sensitive to MPTP. Methods: To test this hypothesis, male mice received chronic low or high doses of MPH and were exposed to saline or MPTP following a 1-week washout. Quinone formation in the striatum was examined via dot blot, and striatal GSH was quantified using a glutathione assay. Results: Indeed, quinone formation increased with increasing doses of methylphenidate. Additionally, methylphenidate dose-dependently resulted in a depletion of glutathione, which was further depleted following MPTP treatment. Conclusions: Thus, the increased sensitivity of dopamine neurons to MPTP toxicity following chronic methylphenidate exposure may be due to quinone production and subsequent depletion of glutathione.

A dissertation submitted in partial fulfilment for the requirements of the degree of Master of Arts in Clinical Psychology at the University of Zululand, South Africa, 2004. / The use of drug stimulation to treat children who have been diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) sparks much controversy. Parental perception of this practise is crucial since it is the parents that have the task of making this sensitive decision. In order to subjectively explicate parental feelings regarding this issue, a qualitative approach was considered appropriate in this study. The study sought to highlight the views of parents around the use of stimulant medication in the treatment of ADHD. In- depth interviews of the four participants were audio taped and then transcribed verbatim. The interviews were unstructured and an open- ended question guideline was utilised. The interviews underwent stringent thematic analysis. Amongst others, the major themes that emerged were those of guilt, frustration, resignation and the strained mother- child relations associated with infant behaviour and the diagnosis. Findings revealed mixed feelings around the use of medication with Ritalin being the most commonly prescribed. However, even though there are mixed feelings associated with medication use, the positive outcomes of this practise outweigh the negative aspects. Although the benefits are great, the future risk of long-term use of stimulant medication is unknown

Methylphenidate (MPH) is the most commonly prescribed drug to treat Attention Deficit Hyperactivity Disorder (ADHD). ADHD is now considered a life-long disorder; therefore, patients take MPH from adolescence into adulthood, highlighting the need for research studying chronic MPH use. MPH increases dopamine and norepinephrine within the synaptic cleft; therefore, chronic use of MPH may lead to changes within important dopaminergic pathways. One pathway, the mesolimbic pathway, includes the hippocampus, an area where adult neurogenesis occurs. We investigated the effects of chronic low and high doses of MPH on neurogenesis and examined levels of a few key proteins linked to cell proliferation in the hippocampus. Low dose MPH appears to increase cell proliferation and cell survival in the hippocampus, and these effects are accompanied by increases in vascular endothelial growth factor (VEGF), the receptor for brain-derived neurotrophic factor (TrkB), and beta-catenin. While high dose MPH may initially increase neuronal proliferation, newly-generated neurons are unable to survive long-term, and decreases in VEGF, TrkB, and beta-catenin are observed with chronic high dose MPH. Another major dopaminergic pathway is the nigrostriatal pathway, which is involved in motor control and degenerates with Parkinson’s disease. Chronic use of MPH appears to sensitize dopaminergic neurons within this pathway to the Parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), but the cause of this sensitization is unknown. The autooxidation of excess dopamine forms dopamine-quinones that lead to free radical production, but the antioxidant, glutathione, can protect neurons. However, we showed that chronic MPH increases dopamine-quinone formation and causes a subsequent glutathione depletion within the striatum. Therefore, oxidative stress may sensitize dopamine neurons to MPTP. We also assessed the vulnerability of dopaminergic neurons in the nigrostriatal pathway to MPTP after chronic MPH in females. Interestingly, proestrus (high estrogen) females were more sensitive to MPTP than anestrus (low estrogen) females. Similar to males, chronic MPH caused a depletion in glutathione that was further decreased following MPTP exposure. However, chronic MPH did not significantly alter dopaminergic neuronal numbers or quinone formation in females. These studies highlight some of the potential effects of chronic MPH use.

The term cognitive enhancers are substances that increase cognitive performance. The stimulant methylphenidate is commonly used as a medication for attention deficit hyperactive disorder and is highly popular as a cognitive enhancer. One of its theorized mechanisms of action is to enhance working memory. This systematic review aims to examine literature that tests the effect of methylphenidate on cognitive performance, specifically working memory, in healthy subjects. Following the PRISMA guidelines, a systematic search was conducted on Web of Science, Scopus, and Medline Ebsco on 1st March 2022. Articles were selected based on the predetermined eligibility criteria. Of the ten selected articles, three found a significant effect of methylphenidate on working memory, and one found a significant effect on spatial working memory. The studies produced varied results due to differential use of working memory tasks and methylphenidate dosage. Further studies on how methylphenidate affects working memory are needed.

Background. Numerous clinical trials demonstrate the efficacy of medication and behavioral treatment for Attention-Deficit/Hyperactivity Disorder (ADHD) in children, but provision of behavioral treatment for ADHD is limited in community clinics and only the pharmacological treatment is the standard care for children with ADHD. The current study evaluated the treatment effectiveness of combining psychosocial treatment to methylphenidate and to compare this combined treatment with medication alone in treating ADHD in children of a community mental health center in Hong Kong. Psychosocial treatment consisted of parent training and child intervention. The treatment group for children was a 24-week problem solving, anger coping, and social skills training program. Parent training consisted of 18 weekly sessions, highlighting parenting as an integration of elements of cognition, emotion, and behavior, as well as introducing effective parenting techniques based on social learning principles. Method. A group of 146 consecutive child patients with ADHD symptoms attending Yaumatei Child Psychiatric Center were invited for screening their eligibility of participating in this study. A randomized group comparison design was used with two treatment conditions (medication-only; combined medication and psychosocial treatment) and four assessment time points. Ninety eligible child-parent dyads were randomly allocated to the combined treatment condition or medication-only condition. Treatment outcomes were assessed in multiple domains at pre-intervention and post-intervention, and at 6-month and 12-month follow-ups. Data was analyzed through intent-to-treat mixed-effects regression model. / Conclusions. The combined treatment condition not only yielded significantly greater benefits than the medication-only condition on primary ADHD symptoms, but also other advantages in terms of conduct problem and adaptive functioning outcomes. / Results. Regarding ADHD symptoms, children in combined treatment condition showed significantly greater improvement than those given medication alone at post-treatment assessment. Combined treatment also proved better than medication alone in several other domains, such as oppositional behavior, a child's performance on computerized test, parenting behavior, and parental accurate knowledge of ADHD. Parental treatment-related attributions were also found to be changing over the course of treatment. Follow-up assessments revealed that children in the combined treatment condition maintained greater reduction in oppositional behavior one year after the completion of psychosocial treatment. / So Yuk-chi. / "May 2005." / Adviser: Patrick W. L. Leung. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 4119. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 222-247). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.

Introdução: O metilfenidato de liberação imediata (MFD-LI) é um psicofármaco receitado mundialmente para o tratamento do Transtorno de Déficit de Atenção/hiperatividade (TDAH). Embora eficaz, o MFD-LI está associado a problemas de adesão ao tratamento, uma vez que os pacientes necessitam ingerir os comprimidos várias vezes ao dia. O Spheroidal Oral Drug Absorption System (SODAS™) é uma formulação de metilfenidato de liberação prolongada (MFD-LP) que mimetiza a administração de MFD-LI duas vezes ao dia, e que apresenta menor flutuação nos níveis séricos. Nesta formulação, cinqüenta por cento dos grânulos com revestimento para liberação entérica são liberados aproximadamente 4 horas após a administração, proporcionando um perfil de ação semelhante a duas tomadas ao dia do MFD-LI. O MFD SODAS™ libera de imediato 50% do medicamento, proporcionando um rápido início de ação quando comparado ao sistema de liberação OROS®. Poucos estudos avaliaram a troca do MFD-LI para o MFD-LP, sendo que desses, apenas crianças e adolescentes foram avaliados, e nenhum verificou os preditores de insatisfação da troca do MFD-LI para o MFD-LP. Objetivos: Este estudo tem como objetivo avaliar os sintomas de TDAH, ou preditores de insatisfação e/ou desistência do tratamento naqueles pacientes clinicamente estáveis que fizeram a troca do MDF-LI para o MFD SODAS™. Método: Os critérios de inclusão foram: diagnóstico de TDAH de acordo com os critérios do DSM-IV, e estabilidade de sintomas com o uso do MFD-LI. Os critérios de exclusão foram: condição clínica coexistente que pudesse impedir a prescrição de MFD SODAS™; diagnóstico de abuso ou dependência de álcool e/ou drogas de abuso; diagnóstico prévio de retardo mental moderado; tratamento psicoterápico concomitante. Este é um ensaio clínico aberto realizado em oito semanas. Os pacientes foram designados a receber doses de MFD SODAS™ de acordo com a dose de MFD-LI previamente estabelecida. A eficácia foi avaliada através das escalas SNAP-IV e CGI-S, e eventos adversos através da Barkley's Side Effect Rating Scale (SERS). Foi solicitado aos participantes que classificassem sua satisfação com o tratamento através de uma escala Likert de 5 pontos. Também foram avaliados os seguintes potenciais preditores de resposta: sexo, idade, etnia, nível socioeconômico, comorbidades, subtipos de TDAH, resultados das escalas SNAP-IV e SERS no baseline, tempo de tratamento, tratamento farmacológico concomitante, dose de MFD-LI prévia ao início do estudo e a existência de pausa do tratamento nos finais de semana. Resultados: A partir de uma amostra total de 207 crianças, adolescentes e adultos (provenientes do ambulatório adulto e infantil de transtorno de déficit de atenção/hiperatividade do Hospital de Clínicas de Porto Alegre) foi possível contatar 133 pacientes, os quais sessenta e dois pacientes foram elegíveis a participar do estudo, e 47 completaram as oito semanas de tratamento. Não se encontrou diferença significativa no escore total do SNAP-IV durante o protocolo - baseline, semana 4 e 8 [F(1, 51,26) =0,012; p=0,913]. Ao todo, 46 (74,2%) dos pacientes relataram estar satisfeitos com o novo tratamento, 16 (25,8%) estavam insatisfeitos ou saíram do protocolo. Nas análises univariadas, foi detectada uma tendência para a associação entre etnia e insatisfação (p=0.05). Não se encontrou uma diferença significativa nos escores da SERS durante o ensaio clínico [F(1, 111,49) =0,748; p=0,389]. Em onze eventos adversos ocorreram ao menos 5% em alguma das avaliações (baseline, 4ª ou 8ª semana). Um adulto, que apresentava uma doença cardiovascular previamente ao estudo, apresentou um acidente vascular cerebral hemorrágico (AVCH) após a quarta semana de tratamento, evoluindo ao óbito após três semanas. Conclusão: Poucos estudos abordaram os sintomas de TDAH após a troca do MFD-LI para qualquer formulação de MFD-LP, e nenhum estudo prévio foi conduzido em populações de países em desenvolvimento ou em amostras com adultos. A taxa de satisfação encontrada (74,2%) na troca do MFD-LI para MFD SODAS™ possivelmente reflete a conveniência da dose única diária deste MFD-LP, como já especulado em estudos prévios. Não foram identificados fatores preditores de insatisfação. O número médio de efeitos colaterais pode ser considerado alto, mas isso pode ser o resultado do uso de uma escala de avaliação adequada, diferentemente do relato espontâneo do evento adverso. Não foi possível encontrar uma relação direta entre os efeitos do MFD SODAS™ e a morte por AVCH ocorrida em um dos sujeitos da amostra. Entretanto, o evento cardiovascular ocorrido sugere extrema cautela ao medicar pacientes com doenças cardiovasculares, conforme proposto pelo FDA. Os achados desse estudo sugerem que o MFD SODAS™ possui eficácia e perfil de eventos adversos similares ao MFD-LI. / Introduction: Immediate-release methylphenidate (MPH-IR) is a pharmacological treatment prescribed worldwide for patients with attention-deficit/hyperactivity disorder (ADHD). The MPH-IR, although highly efficacious, need to be used more than once a day, and consequently might be associated with poor adherence. The Spheroidal Oral Drug Absorption System (SODAS™) is one type of MPH-ER (Extended-release methylphenidate) that mimics the twice-daily administration of MPH-immediate release, but presents less peak and trough fluctuations. This formulation allows the immediate release of 50% of the drug, providing a rapid onset if compared with OROS® formulation. Few studies have evaluated specifically the switching from MPH-IR to MPH-ER. All previous studies accessed only children and adolescents; none evaluated switching to MPH SODAS™ and no predictors of treatment dissatisfaction were mentioned. Objectives: The present study aims to assess ADHD symptoms for 08 weeks after switching from MPH-IR to MPH SODAS™ in clinically stable patients, and to identify predictors of dissatisfaction with MPH SODAS™, and/ or withdrawal from the protocol. Method: The inclusion criteria were: ADHD diagnosis according to the DSM-IV criteria and clinical stability with MPH-IR. The exclusion criteria were: a clinically coexisting medical condition interfering with the administration of MPH SODAS™; previous diagnosis of alcohol and/or drug abuse or dependence; previous diagnosis of moderate mental retardation; concomitant psychotherapy. This is an 8-week open clinical trial. Patients were assigned to doses of MPH SODAS™ according to their pre-study dose of MPH-IR. Assessment of efficacy and side effects was performed by means of the SNAP-IV, CGI-S, Barkley's Side Effect Rating Scale (SERS). Subjects were also asked to report their satisfaction with the treatment in a 5-point Likert scale. We also evaluated the following potential predictors of treatment response: sex, age, ethnicity, socioeconomic status, comorbidities, baseline scores on the SNAP-IV, and SERS, length of treatment, concomitant treatment, previous prescribed dose of MPH-IR, and pause of treatment on weekends. Results: From a total sample of 207 children, adolescents and adults (enrolled from the ADHD outpatient clinic at both Adult and Child and Adolescent Psychiatric Division of Hospital de Clínicas de Porto Alegre) we were able to re-contact 133 patients, where sixty-two patients were eligible to the clinical trial, and 47 completed the 08 weeks of treatment. There was no significant change in the total score of the SNAP-IV during the protocol – baseline, week 4 and 8 [F(1, 51.26)=0.012; p=0.913]. Overall, 46 (74.2%) patients had reported to be satisfied with the new treatment, and 16 (25.8%) were dissatisfied or withdrew from the protocol. In univariate analyses, only ethnicity (p=0.05) were associated with dissatisfaction. No significant change in the SERS score was found during the protocol [F(1, 111.49)=0.748; p=0.389]. Eleven adverse events occurring in at least 5% of the group in any assessment (baseline, 04 or 08 weeks) were observed according to SERS. One adult, with previous cardiovascular disease, presented a hemorrhagic cerebral vascular accident (CVA) after the forth week assessment, resulting in her obit. Conclusion: There is a scarcity of research assessing the switch from MPH-IR to different forms of MPH-ER, and none across the life cycle or in populations from developing countries. The 74.2% of satisfaction with the new treatment may reflect the convenience of the once-a-day dosing of the MPH SODAS™. No predictor of dissatisfaction/withdrawal from the trial was found. The number of adverse events reported during the protocol could be considered high, but this can be the result of the use of an appropriate assessment scale, rather than monitoring only by spontaneous report. It was not possible to find a direc relationship between the MPH SODAS™ and death from a CVA occurred in one of the subjects. However, the cardiovascular event found during the trial, suggest extreme caution when medicating patients with cardiovascular diseases as recently proposed by the FDA. Findings from this study suggest that MPH SODAS™ has similar efficacy and adverse event profile than MPH-IR.

Introdução: O metilfenidato de liberação imediata (MFD-LI) é um psicofármaco receitado mundialmente para o tratamento do Transtorno de Déficit de Atenção/hiperatividade (TDAH). Embora eficaz, o MFD-LI está associado a problemas de adesão ao tratamento, uma vez que os pacientes necessitam ingerir os comprimidos várias vezes ao dia. O Spheroidal Oral Drug Absorption System (SODAS™) é uma formulação de metilfenidato de liberação prolongada (MFD-LP) que mimetiza a administração de MFD-LI duas vezes ao dia, e que apresenta menor flutuação nos níveis séricos. Nesta formulação, cinqüenta por cento dos grânulos com revestimento para liberação entérica são liberados aproximadamente 4 horas após a administração, proporcionando um perfil de ação semelhante a duas tomadas ao dia do MFD-LI. O MFD SODAS™ libera de imediato 50% do medicamento, proporcionando um rápido início de ação quando comparado ao sistema de liberação OROS®. Poucos estudos avaliaram a troca do MFD-LI para o MFD-LP, sendo que desses, apenas crianças e adolescentes foram avaliados, e nenhum verificou os preditores de insatisfação da troca do MFD-LI para o MFD-LP. Objetivos: Este estudo tem como objetivo avaliar os sintomas de TDAH, ou preditores de insatisfação e/ou desistência do tratamento naqueles pacientes clinicamente estáveis que fizeram a troca do MDF-LI para o MFD SODAS™. Método: Os critérios de inclusão foram: diagnóstico de TDAH de acordo com os critérios do DSM-IV, e estabilidade de sintomas com o uso do MFD-LI. Os critérios de exclusão foram: condição clínica coexistente que pudesse impedir a prescrição de MFD SODAS™; diagnóstico de abuso ou dependência de álcool e/ou drogas de abuso; diagnóstico prévio de retardo mental moderado; tratamento psicoterápico concomitante. Este é um ensaio clínico aberto realizado em oito semanas. Os pacientes foram designados a receber doses de MFD SODAS™ de acordo com a dose de MFD-LI previamente estabelecida. A eficácia foi avaliada através das escalas SNAP-IV e CGI-S, e eventos adversos através da Barkley's Side Effect Rating Scale (SERS). Foi solicitado aos participantes que classificassem sua satisfação com o tratamento através de uma escala Likert de 5 pontos. Também foram avaliados os seguintes potenciais preditores de resposta: sexo, idade, etnia, nível socioeconômico, comorbidades, subtipos de TDAH, resultados das escalas SNAP-IV e SERS no baseline, tempo de tratamento, tratamento farmacológico concomitante, dose de MFD-LI prévia ao início do estudo e a existência de pausa do tratamento nos finais de semana. Resultados: A partir de uma amostra total de 207 crianças, adolescentes e adultos (provenientes do ambulatório adulto e infantil de transtorno de déficit de atenção/hiperatividade do Hospital de Clínicas de Porto Alegre) foi possível contatar 133 pacientes, os quais sessenta e dois pacientes foram elegíveis a participar do estudo, e 47 completaram as oito semanas de tratamento. Não se encontrou diferença significativa no escore total do SNAP-IV durante o protocolo - baseline, semana 4 e 8 [F(1, 51,26) =0,012; p=0,913]. Ao todo, 46 (74,2%) dos pacientes relataram estar satisfeitos com o novo tratamento, 16 (25,8%) estavam insatisfeitos ou saíram do protocolo. Nas análises univariadas, foi detectada uma tendência para a associação entre etnia e insatisfação (p=0.05). Não se encontrou uma diferença significativa nos escores da SERS durante o ensaio clínico [F(1, 111,49) =0,748; p=0,389]. Em onze eventos adversos ocorreram ao menos 5% em alguma das avaliações (baseline, 4ª ou 8ª semana). Um adulto, que apresentava uma doença cardiovascular previamente ao estudo, apresentou um acidente vascular cerebral hemorrágico (AVCH) após a quarta semana de tratamento, evoluindo ao óbito após três semanas. Conclusão: Poucos estudos abordaram os sintomas de TDAH após a troca do MFD-LI para qualquer formulação de MFD-LP, e nenhum estudo prévio foi conduzido em populações de países em desenvolvimento ou em amostras com adultos. A taxa de satisfação encontrada (74,2%) na troca do MFD-LI para MFD SODAS™ possivelmente reflete a conveniência da dose única diária deste MFD-LP, como já especulado em estudos prévios. Não foram identificados fatores preditores de insatisfação. O número médio de efeitos colaterais pode ser considerado alto, mas isso pode ser o resultado do uso de uma escala de avaliação adequada, diferentemente do relato espontâneo do evento adverso. Não foi possível encontrar uma relação direta entre os efeitos do MFD SODAS™ e a morte por AVCH ocorrida em um dos sujeitos da amostra. Entretanto, o evento cardiovascular ocorrido sugere extrema cautela ao medicar pacientes com doenças cardiovasculares, conforme proposto pelo FDA. Os achados desse estudo sugerem que o MFD SODAS™ possui eficácia e perfil de eventos adversos similares ao MFD-LI. / Introduction: Immediate-release methylphenidate (MPH-IR) is a pharmacological treatment prescribed worldwide for patients with attention-deficit/hyperactivity disorder (ADHD). The MPH-IR, although highly efficacious, need to be used more than once a day, and consequently might be associated with poor adherence. The Spheroidal Oral Drug Absorption System (SODAS™) is one type of MPH-ER (Extended-release methylphenidate) that mimics the twice-daily administration of MPH-immediate release, but presents less peak and trough fluctuations. This formulation allows the immediate release of 50% of the drug, providing a rapid onset if compared with OROS® formulation. Few studies have evaluated specifically the switching from MPH-IR to MPH-ER. All previous studies accessed only children and adolescents; none evaluated switching to MPH SODAS™ and no predictors of treatment dissatisfaction were mentioned. Objectives: The present study aims to assess ADHD symptoms for 08 weeks after switching from MPH-IR to MPH SODAS™ in clinically stable patients, and to identify predictors of dissatisfaction with MPH SODAS™, and/ or withdrawal from the protocol. Method: The inclusion criteria were: ADHD diagnosis according to the DSM-IV criteria and clinical stability with MPH-IR. The exclusion criteria were: a clinically coexisting medical condition interfering with the administration of MPH SODAS™; previous diagnosis of alcohol and/or drug abuse or dependence; previous diagnosis of moderate mental retardation; concomitant psychotherapy. This is an 8-week open clinical trial. Patients were assigned to doses of MPH SODAS™ according to their pre-study dose of MPH-IR. Assessment of efficacy and side effects was performed by means of the SNAP-IV, CGI-S, Barkley's Side Effect Rating Scale (SERS). Subjects were also asked to report their satisfaction with the treatment in a 5-point Likert scale. We also evaluated the following potential predictors of treatment response: sex, age, ethnicity, socioeconomic status, comorbidities, baseline scores on the SNAP-IV, and SERS, length of treatment, concomitant treatment, previous prescribed dose of MPH-IR, and pause of treatment on weekends. Results: From a total sample of 207 children, adolescents and adults (enrolled from the ADHD outpatient clinic at both Adult and Child and Adolescent Psychiatric Division of Hospital de Clínicas de Porto Alegre) we were able to re-contact 133 patients, where sixty-two patients were eligible to the clinical trial, and 47 completed the 08 weeks of treatment. There was no significant change in the total score of the SNAP-IV during the protocol – baseline, week 4 and 8 [F(1, 51.26)=0.012; p=0.913]. Overall, 46 (74.2%) patients had reported to be satisfied with the new treatment, and 16 (25.8%) were dissatisfied or withdrew from the protocol. In univariate analyses, only ethnicity (p=0.05) were associated with dissatisfaction. No significant change in the SERS score was found during the protocol [F(1, 111.49)=0.748; p=0.389]. Eleven adverse events occurring in at least 5% of the group in any assessment (baseline, 04 or 08 weeks) were observed according to SERS. One adult, with previous cardiovascular disease, presented a hemorrhagic cerebral vascular accident (CVA) after the forth week assessment, resulting in her obit. Conclusion: There is a scarcity of research assessing the switch from MPH-IR to different forms of MPH-ER, and none across the life cycle or in populations from developing countries. The 74.2% of satisfaction with the new treatment may reflect the convenience of the once-a-day dosing of the MPH SODAS™. No predictor of dissatisfaction/withdrawal from the trial was found. The number of adverse events reported during the protocol could be considered high, but this can be the result of the use of an appropriate assessment scale, rather than monitoring only by spontaneous report. It was not possible to find a direc relationship between the MPH SODAS™ and death from a CVA occurred in one of the subjects. However, the cardiovascular event found during the trial, suggest extreme caution when medicating patients with cardiovascular diseases as recently proposed by the FDA. Findings from this study suggest that MPH SODAS™ has similar efficacy and adverse event profile than MPH-IR.

Introdução: O metilfenidato de liberação imediata (MFD-LI) é um psicofármaco receitado mundialmente para o tratamento do Transtorno de Déficit de Atenção/hiperatividade (TDAH). Embora eficaz, o MFD-LI está associado a problemas de adesão ao tratamento, uma vez que os pacientes necessitam ingerir os comprimidos várias vezes ao dia. O Spheroidal Oral Drug Absorption System (SODAS™) é uma formulação de metilfenidato de liberação prolongada (MFD-LP) que mimetiza a administração de MFD-LI duas vezes ao dia, e que apresenta menor flutuação nos níveis séricos. Nesta formulação, cinqüenta por cento dos grânulos com revestimento para liberação entérica são liberados aproximadamente 4 horas após a administração, proporcionando um perfil de ação semelhante a duas tomadas ao dia do MFD-LI. O MFD SODAS™ libera de imediato 50% do medicamento, proporcionando um rápido início de ação quando comparado ao sistema de liberação OROS®. Poucos estudos avaliaram a troca do MFD-LI para o MFD-LP, sendo que desses, apenas crianças e adolescentes foram avaliados, e nenhum verificou os preditores de insatisfação da troca do MFD-LI para o MFD-LP. Objetivos: Este estudo tem como objetivo avaliar os sintomas de TDAH, ou preditores de insatisfação e/ou desistência do tratamento naqueles pacientes clinicamente estáveis que fizeram a troca do MDF-LI para o MFD SODAS™. Método: Os critérios de inclusão foram: diagnóstico de TDAH de acordo com os critérios do DSM-IV, e estabilidade de sintomas com o uso do MFD-LI. Os critérios de exclusão foram: condição clínica coexistente que pudesse impedir a prescrição de MFD SODAS™; diagnóstico de abuso ou dependência de álcool e/ou drogas de abuso; diagnóstico prévio de retardo mental moderado; tratamento psicoterápico concomitante. Este é um ensaio clínico aberto realizado em oito semanas. Os pacientes foram designados a receber doses de MFD SODAS™ de acordo com a dose de MFD-LI previamente estabelecida. A eficácia foi avaliada através das escalas SNAP-IV e CGI-S, e eventos adversos através da Barkley's Side Effect Rating Scale (SERS). Foi solicitado aos participantes que classificassem sua satisfação com o tratamento através de uma escala Likert de 5 pontos. Também foram avaliados os seguintes potenciais preditores de resposta: sexo, idade, etnia, nível socioeconômico, comorbidades, subtipos de TDAH, resultados das escalas SNAP-IV e SERS no baseline, tempo de tratamento, tratamento farmacológico concomitante, dose de MFD-LI prévia ao início do estudo e a existência de pausa do tratamento nos finais de semana. Resultados: A partir de uma amostra total de 207 crianças, adolescentes e adultos (provenientes do ambulatório adulto e infantil de transtorno de déficit de atenção/hiperatividade do Hospital de Clínicas de Porto Alegre) foi possível contatar 133 pacientes, os quais sessenta e dois pacientes foram elegíveis a participar do estudo, e 47 completaram as oito semanas de tratamento. Não se encontrou diferença significativa no escore total do SNAP-IV durante o protocolo - baseline, semana 4 e 8 [F(1, 51,26) =0,012; p=0,913]. Ao todo, 46 (74,2%) dos pacientes relataram estar satisfeitos com o novo tratamento, 16 (25,8%) estavam insatisfeitos ou saíram do protocolo. Nas análises univariadas, foi detectada uma tendência para a associação entre etnia e insatisfação (p=0.05). Não se encontrou uma diferença significativa nos escores da SERS durante o ensaio clínico [F(1, 111,49) =0,748; p=0,389]. Em onze eventos adversos ocorreram ao menos 5% em alguma das avaliações (baseline, 4ª ou 8ª semana). Um adulto, que apresentava uma doença cardiovascular previamente ao estudo, apresentou um acidente vascular cerebral hemorrágico (AVCH) após a quarta semana de tratamento, evoluindo ao óbito após três semanas. Conclusão: Poucos estudos abordaram os sintomas de TDAH após a troca do MFD-LI para qualquer formulação de MFD-LP, e nenhum estudo prévio foi conduzido em populações de países em desenvolvimento ou em amostras com adultos. A taxa de satisfação encontrada (74,2%) na troca do MFD-LI para MFD SODAS™ possivelmente reflete a conveniência da dose única diária deste MFD-LP, como já especulado em estudos prévios. Não foram identificados fatores preditores de insatisfação. O número médio de efeitos colaterais pode ser considerado alto, mas isso pode ser o resultado do uso de uma escala de avaliação adequada, diferentemente do relato espontâneo do evento adverso. Não foi possível encontrar uma relação direta entre os efeitos do MFD SODAS™ e a morte por AVCH ocorrida em um dos sujeitos da amostra. Entretanto, o evento cardiovascular ocorrido sugere extrema cautela ao medicar pacientes com doenças cardiovasculares, conforme proposto pelo FDA. Os achados desse estudo sugerem que o MFD SODAS™ possui eficácia e perfil de eventos adversos similares ao MFD-LI. / Introduction: Immediate-release methylphenidate (MPH-IR) is a pharmacological treatment prescribed worldwide for patients with attention-deficit/hyperactivity disorder (ADHD). The MPH-IR, although highly efficacious, need to be used more than once a day, and consequently might be associated with poor adherence. The Spheroidal Oral Drug Absorption System (SODAS™) is one type of MPH-ER (Extended-release methylphenidate) that mimics the twice-daily administration of MPH-immediate release, but presents less peak and trough fluctuations. This formulation allows the immediate release of 50% of the drug, providing a rapid onset if compared with OROS® formulation. Few studies have evaluated specifically the switching from MPH-IR to MPH-ER. All previous studies accessed only children and adolescents; none evaluated switching to MPH SODAS™ and no predictors of treatment dissatisfaction were mentioned. Objectives: The present study aims to assess ADHD symptoms for 08 weeks after switching from MPH-IR to MPH SODAS™ in clinically stable patients, and to identify predictors of dissatisfaction with MPH SODAS™, and/ or withdrawal from the protocol. Method: The inclusion criteria were: ADHD diagnosis according to the DSM-IV criteria and clinical stability with MPH-IR. The exclusion criteria were: a clinically coexisting medical condition interfering with the administration of MPH SODAS™; previous diagnosis of alcohol and/or drug abuse or dependence; previous diagnosis of moderate mental retardation; concomitant psychotherapy. This is an 8-week open clinical trial. Patients were assigned to doses of MPH SODAS™ according to their pre-study dose of MPH-IR. Assessment of efficacy and side effects was performed by means of the SNAP-IV, CGI-S, Barkley's Side Effect Rating Scale (SERS). Subjects were also asked to report their satisfaction with the treatment in a 5-point Likert scale. We also evaluated the following potential predictors of treatment response: sex, age, ethnicity, socioeconomic status, comorbidities, baseline scores on the SNAP-IV, and SERS, length of treatment, concomitant treatment, previous prescribed dose of MPH-IR, and pause of treatment on weekends. Results: From a total sample of 207 children, adolescents and adults (enrolled from the ADHD outpatient clinic at both Adult and Child and Adolescent Psychiatric Division of Hospital de Clínicas de Porto Alegre) we were able to re-contact 133 patients, where sixty-two patients were eligible to the clinical trial, and 47 completed the 08 weeks of treatment. There was no significant change in the total score of the SNAP-IV during the protocol – baseline, week 4 and 8 [F(1, 51.26)=0.012; p=0.913]. Overall, 46 (74.2%) patients had reported to be satisfied with the new treatment, and 16 (25.8%) were dissatisfied or withdrew from the protocol. In univariate analyses, only ethnicity (p=0.05) were associated with dissatisfaction. No significant change in the SERS score was found during the protocol [F(1, 111.49)=0.748; p=0.389]. Eleven adverse events occurring in at least 5% of the group in any assessment (baseline, 04 or 08 weeks) were observed according to SERS. One adult, with previous cardiovascular disease, presented a hemorrhagic cerebral vascular accident (CVA) after the forth week assessment, resulting in her obit. Conclusion: There is a scarcity of research assessing the switch from MPH-IR to different forms of MPH-ER, and none across the life cycle or in populations from developing countries. The 74.2% of satisfaction with the new treatment may reflect the convenience of the once-a-day dosing of the MPH SODAS™. No predictor of dissatisfaction/withdrawal from the trial was found. The number of adverse events reported during the protocol could be considered high, but this can be the result of the use of an appropriate assessment scale, rather than monitoring only by spontaneous report. It was not possible to find a direc relationship between the MPH SODAS™ and death from a CVA occurred in one of the subjects. However, the cardiovascular event found during the trial, suggest extreme caution when medicating patients with cardiovascular diseases as recently proposed by the FDA. Findings from this study suggest that MPH SODAS™ has similar efficacy and adverse event profile than MPH-IR.

Examines whether the reinforcing properties of drugs of abuse were altered in adulthood by methylphenidate, more commonly known as Ritalin. Subjects were 108 rats of Sprague-Dawley descent (Harlan). Methylphenidate, or saline was administered daily to the subjects from the postnatal period (11-20 days old). The rats preference for morphine during early adulthood was measured using conditioned place preference. The number of dopamine D₂ receptors was measured in each rat and the correlation between receptor number and morphine preference was determined. Results indicate that rats pretreated with methylphenidate showed greater preference for morphine than saline pretreated rats and suggests that exposure to methylphenidate during the postnatal period increases the rewarding value of morphine.