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Poor adherence is a major concern in the treatment of attention-deficit/hyperactivity disorder (ADHD). The objective of this study was to evaluate factors linked to early interruption of and low adherence to treatment with osmotic-release oral system methylphenidate hydrochloride (OROS-MPH) in pediatric patients with ADHD. A total of 1353 young people (age 6–17 years) with a diagnosis of ADHD who newly started OROS-MPH were extracted from the pharmacoepidemiological data of 3 million people in Japan. The cohort was retrospectively surveyed every month for 12 months. Ten possible risk factors were extracted from the data and analyzed by multivariable logistic regression. Sensitivity analysis was conducted to ensure the robustness of the analysis. The results revealed that treatment adherence was generally poor, with a tendency for discontinuation in the early stage. Multivariable logistic regression results showed that adherence is reduced by female sex, lower starting dose, and concomitant atomoxetine or hypnotics. These findings may help clinicians to predict the risk of poor adherence in the early stage of treatment and improve not only patients’ symptoms, but also their quality of life.

Background Methylphenidate (MPH) hydrochloride is used as a first-line treatment for attention deficit hyperactivity disorder (ADHD). However, there is concern that this treatment may be associated with increased risk of refractive disorder. The aim of this study was to investigate the effect of MPH therapy on myopic shifts in refraction in children diagnosed with ADHD. Methods This study, children with ADHD and meeting inclusion criteria were examined before the initiation of MPH treatment and 3, 6 and 12 months after the initiation of treatment. Twenty age-gender-matched participants who applied to the outpatient ophthalmology clinic with various complaints were included in the study as a control group. Cycloplegic refraction examination and detailed eye measurements were performed at each visit. Results Nineteen patients were included in this study and the group consisted of 11 (57.9%) females and 8 (42.1%) males. The mean age of patients was 11.3 +/- 2. (range: 8-18) years. During 12 months of use of MPH, the spherical equivalent changed from -0.36 +/- 1.08 to -0.39 +/- 1.05, and this difference was not statistically significant (P = .187). Axial length ranged from 22.92 +/- 0.66. There was a change to 22.93 +/- 0.62, and this difference was not statistically significant (P = .076). In the control group, the spherical equivalent changed from -0.43 +/- 0.62 to -0.56 +/- 0.84, and this difference was statistically significant. (P = .012) There was a change in the axial length from 22.97 +/- 0.78 to 22.99 +/- 0.62, and this difference was statistically significant (P = .015). Conclusions No significant changes spherical equivalent and axial length were detected during 12-month MPH use, but the increased spherical equivalent and axial length in the control group in the similar age group may indicate that MPH may reduce myopic shifts in refraction progression through dopamine, similar to in vivo studies. What's newWhat's known Myopia is spreading rapidly in technologically advanced societies. There is strong evidence that myopia develops as the axial length of the eye increases as a result of spending more time indoors and working in close distances in parallel with the increase in education level. Animal studies have shown that decreased dopamine release plays an important role in the development of myopia. The effect of dopamine in slowing or stopping myopia in experimental studies has also been demonstrated in human studies. No significant change in spherical equivalent and axial length was observed in methylphenidate users compared with control patients of similar age group. A significant increase in spherical equivalent and axial length was detected in the control group. This pilot study will shed light on future studies on the safe use of dopamine in the treatment of myopic shifts.

Supplemental digital content is available in the text., Purpose/Background PRC-063 is a once-daily, extended-release oral formulation of methylphenidate hydrochloride developed to provide early and prolonged symptom improvement in patients with attention-deficit/hyperactivity disorder. Methods/Procedures We conducted 3 randomized, open-label crossover studies of the pharmacokinetics of PRC-063 in healthy, nonobese men and women aged 18 to 45 years. PRC-063 (100 mg/d) was compared with immediate-release methylphenidate (20 mg, 3 times daily) when administered on a single day under fasted and fed conditions and at steady state (day 5 of repeat dosing under fasted conditions). The pharmacokinetics of PRC-063 administered as capsule contents sprinkled on apple sauce, yoghurt, or ice cream were also investigated. Findings/Results PRC-063 demonstrated biphasic absorption, with 2 distinct peak plasma concentrations. Intake of a high-fat, high-calorie meal did not increase the peak plasma methylphenidate concentration (Cmax) or extent of absorption (area under the curve), however; it resulted in slower uptake versus a fasted state. During repeated dosing, steady state was reached with no further accumulation of methylphenidate from day 3. At steady state, PRC-063 gave higher evening and trough plasma methylphenidate levels than immediate-release methylphenidate (3 times daily). The pharmacokinetics of PRC-063 sprinkled on food were comparable to that of intact capsules. Reported adverse events (AEs) were consistent with the established safety profile of methylphenidate. There were no serious AEs, but 3 subjects discontinued the repeat-dosing study because of AEs assessed as possibly related to study treatment. Implications/Conclusions Our data indicate that PRC-063 can be taken with or without food or by sprinkling capsule contents on food.

Objectives The aim of this study to compare the clinic efficacy and effects of osmotic release oral system-methylphenidate and atomoxetine on executive function in children and adolescents with attention deficit hyperactivity disorder by a open-label, prospective, randomized controlled trial. Methods The study was performed by 95 cases between ages 6 and 12 years who were diagnosed as attention-deficit/hyperactivity disorder (ADHD) and also 40 control individuals. In this study, Conners' Teacher Rating Scale (CTRS) was used in order to evaluate the efficacy of the treatment. Executive functions were assessed by the performance-based neuropsychological tests and ecological behavioral rating scales. Stroop test, cancellation test, and serial digit learning test were applied to performance based neuropsychological tests. Behavior Rating Inventory of Executive Function tests (BRIEFs) were used as behavioral assessment scales. Results Among the ADHD groups, a reduction of over 40% in the CTRS subtest scores used to evaluate the efficacy of the treatment was considered to be an improvement, and no significant difference was found for both drugs. Both Osmotic Release Oral System-Methylphenidate Hydrochloride (OROS-MPH) and atomoxetine (ATX) significantly improved scores in neuropsychological tests. Conclusion Atomoxetine and OROS-MPH treatments have shown similar efficacy in clinical recovery and improvement on executive functions. However, disturbances in executive functions observed in children with ADHD are persistent despite treatment, when compared with the control group.

O uso de medicamentos, por pessoas saudáveis, para melhorar o funcionamento do cérebro e aprimorar o desempenho cognitivo pode ser chamado de aprimoramento cognitivo farmacológico ou de doping intelectual. Um dos medicamentos mais utilizados no Brasil com esta finalidade é o Cloridrato de Metilfenidato, comercializado com o nome de Ritalina ou Concerta. O presente artigo objetivou compreender, por meio de uma revisão de literatura, como o cloridrato metilfenidato tem sido utilizado no aprimoramento cognitivo farmacológico e a relação deste fenômeno com a medicalização social. Sabe-se que estes medicamentos tem como efeito imediato o aumento da concentração, mas a longo prazo podem causar supressão do crescimento, aumento da pressão sanguínea, episódios psicóticos, entre outros. Ainda assim, eles tem sido utilizados por estudantes universitários com a finalidade de aumentar sua capacidade produtiva e cumprir prazos e metas. Como esta prática tem ganhado cada vez mais adeptos e o acesso a este medicamento é facilitado, é necessário aprofundar o entendimento deste fenômeno.

The purpose of this study was to determine the relative efficacy of selected drugs in reducing the hyperactivity end increasing the attention span of a ten-year old child who had been medically diagnosed as having brain damage. The evaluation of the effects of three drugs, Chlordiazepoxide (librium), Fluphenasine Hydrochloride (Prolixin), Thioridazine (Mellaril), and a combination of Mellaril and Methylphenidate Hydrochloride (Ritalin), was made by a psychiatrist after consideration of (1) written observations of the child’s school activities during a two-hour period, (2) a tabulation of data based on the observations, (3) reports made by the parents and teacher of the child, and (k) interviews with the subject. This study is important, too, because the child Involved needs help toward living as normal a life as possible. The individual’s behavior drew the attention of her family, her teachers, and her associates. Because it was so abnormal, medical and psychological help were sought for her. The psychiatrist administering the drugs felt that a study would be beneficial. Inasmuch as little controlled experimentation has been done in this area, the study Is potentially significant. It might be indicative of future help for the individuals suffering from brain damage and those most directly concerned with helping them.

Objective Adult and children attention deficit/hyperactivity disorder (ADHD) share similar symptoms and responses to drugs such as methylphenidate (MPH). Yet, in Europe, these drugs remain unlicensed for adults. We aimed to assess the effects of an acute MPH challenge on the four dimensions concentration, impulsivity, tension, and general well-being in ADHD adults, and identify predictors of improvement. Methods Therapeutic Drug Monitoring was performed to measure MPH plasma levels. A Visual Analogue Scale was administered to patients before and after the acute MPH challenge to measure self-reported changes in the four dimensions. Results After the acute MPH challenge, our 71 patients showed significant improvement in concentration and tension. The MPH challenge dose correlated with lower patients' age, greater side effects, increased concentration (p = .008) and decreased tension (p = .001). At multiple linear regression MPH plasma levels and absence of postdose side effects predicted concentration improvement, MPH plasma levels predicted tension improvement. MPH plasma levels were significantly higher in patients who reported an improvement in concentration, tension, and impulsivity compared to nonimprovers (p's from .001 to .004). Conclusions These findings point to the efficacy of MPH challenge in improving concentration and tension in adult ADHD, thus emphasizing the need for a broader treatment access for these patients.

Unused medications have the possibility of being abused, causing serious harm to individuals who were not prescribed the drug. The Food and Drug Administration (FDA) recommends the proper disposal of unused prescribed medications to maintain safety and prevent environmental hazards. However, many of the current disposal techniques do not properly address safety. A drug disposal pouch containing granular activated carbon offers a unique disposal method to deactivate residual or expired medication in a convenient, effective, and safe manner. A robust and validated method for methylphenidate hydrochloride and loxapine succinate was developed using high-performance liquid chromatography (HPLC) and the deactivation efficiency of the disposal system was tested. Methylphenidate hydrochloride was analyzed on a C18 analytical column (250 mm × 4.60 mm, 100Å) using acetonitrile-water (0.05% (v/v) trifluoroacetic acid) as the mobile phase at a flow rate of 1.0 mL/min with a run time of 15 min and retention time of 7.8 min. Loxapine succinate was separated on a C8 100Å (250 mm × 4.6 mm, 5 µm) column maintained at 25 °C using a flow rate of 1.0 mL/min. The run time was 10 min and the retention time of the drug was around 4.6 min. Mobile phase was composed of acetonitrile and water (0.3% triethylamine) at pH 3.0 as 40:60 (v/v). Reference standard solutions (100 µg/mL) for both drugs were prepared by dissolving in mobile phases. These methods provide good linearity (R2 = 0.999) over the range of 5–100 µg/mL for methylphenidate hydrochloride and 0.1–100 µg/mL for loxapine succinate. The assay methods were successfully applied to study the deactivation of these drugs. Keywords: Methylphenidate hydrochloride, Loxapine succinate, Activated carbon, Analytical method development, FDA drug disposal

Purpose Methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) is approved for treatment of attention deficit hyperactivity disorder in patients aged 6 years and older. This article evaluates the pharmacokinetic parameters and relative bioavailability of MPH ERCT when chewed versus swallowed whole. Methods In this open-label, single-dose, 3-period, 3-treatment crossover study, 12 healthy adult volunteers were randomly assigned to treatment sequence. In each period, subjects received a single 40-mg dose of the assigned treatment (MPH ERCT chewed, MPH ERCT swallowed whole, or methylphenidate extended-release oral suspension [MEROS]). Blood samples for pharmacokinetic analysis were collected for 24 hours postdose. Key pharmacokinetic parameters included Cmax, AUC0–t, and AUC0–∞. Findings The geometric mean values for AUC0–t, AUC0–∞, and Cmax were similar for MPH ERCT chewed, MPH ERCT swallowed whole, and MEROS. In all pairwise between-treatment comparisons, the 90% CIs of the geometric mean ratios for AUC0–t, AUC0–∞, and Cmax were fully contained within the bioequivalence range of 80% to 125%. Early exposure over the first 4 hours after dosing (AUC0–4) was similar for MPH ERCT chewed versus swallowed whole; AUC0–4 was approximately 15% lower for MPH ERCT, either chewed or swallowed, compared with MEROS. Each treatment was generally well tolerated. Implications There was no difference in overall rate or extent of exposure of methylphenidate when MPH ERCT was chewed versus swallowed whole by healthy volunteers.

Methylphenidate- and amphetamine-based psychostimulants are the most common medications used to treat the symptoms of attention-deficit/hyperactivity disorder in children. Ocular side effects including dry eyes, mydriasis, accommodation disturbance, and blurry vision are listed in the product monograph but interestingly, are rarely reported in the paediatric literature. Our patient, a 9-year-old boy, presented a significant decrease in visual acuity secondary to accommodation disorder after being treated with methylphenidate hydrochloride controlled release (Biphentin) and lisdexamfetamine (Vyvanse). The unusual acute adverse effect, altered accommodation leading to a decline in visual acuity, emphasizes the importance of considering any change in vision following the introduction of psychostimulant medication as a potential adverse effect. This case highlights the importance of pharmacovigilance especially in paediatrics where data are lacking.

Since the advent of ion exchange resin, it has been widely used in many fields, including drug delivery systems. The drug binds to the resin through an exchange reaction to form a drug–resin complex, which can gradually release drugs through the exchange of physiological ions in the gastrointestinal tract, to realize functions such as taste masking and regulating release. In this study, the complexes of methylphenidate hydrochloride and Amberlite IRP69 were prepared and evaluated to explore the mechanism of complexation, influencing factors and release mechanism at a molecular level. Firstly, with the properties of the selected complexes, molecular dynamics simulation was innovatively used to find that the intermolecular interaction between drug molecules and ion exchange resin molecules is mainly caused by the stacking effect of π and salt bridges. Secondly, with the drug loading status as an indicator, the factors affecting the compounding process of the drug and resin were explored. Finally, the release mechanism of the drug–resin complex was studied by mathematical model fitting. In summary, a variety of methods were used to study the mechanism of complexation and release between drug and resin, providing a theoretical basis for promoting the marketing of ion−exchange resin−mediated oral preparations.

O cloridato de metilfenidato [(dl-treo-metil-2-fenil-2- (2-piperidil) acetato], conhecido como Ritalina é um psicofármaco usado geralmente por pessoas com Transtorno de Déficit de Atenção e Hiperatividade (TDAH) e com narcolepsia, para o seu tratamento. Por se tratar de um medicamento que age no sistema nervoso liberando noradrenalina e dopamina nas fendas sinápticas, incidindo uma excitação nos receptores pós-sinápticos e altera as funções cognitivas do usuário, o uso off label para melhorar o desempenho cognitivo está sendo cada vez mais comum. Este tipo de medicamento deve ser usado de forma racional, bem como qualquer outra medicação, pois podem causar efeitos adversos e dependência. Em vista do exposto, este estudo objetivou avaliar, por meio da literatura, a forma correta de uso do metilfenidato, o uso indiscriminado, off label e os problemas de saúde que o uso prolongado pode desencadear no usuário, assim como a importância da atenção farmacêutica para um tratamento eficaz com metilfenidato. Para isso, foi realizada uma revisão integrativa da literatura e os artigos para esta revisão foram coletados nos seguintes portais de pesquisa: SciELO, BVS e Lilacs. Após a coleta, foram selecionados 21 estudos para compor os resultados. Foi possível perceber que o uso indiscriminado do cloridrato de metilfenidato tem sido realizado com frequência por muitas pessoas, principalmente por estudantes, podendo levar a complicações sérias e o aparecimento de efeitos adversos graves, principalmente eventos cardiovasculares como taquicardia e hipertensão, transtornos psiquiátricos como depressão, psicose e dependência química, bem como do sistema neurológico como discinesia, contrações musculares involuntárias e espasmos, entre outros.

Film forming systems offer a number of advantages for topical and transdermal drug delivery, in particular enabling production of a supersaturated state which can greatly improve drug absorption and bioavailability. However the suitability of individual film forming polymers to stabilise the supersaturated state and optimise delivery of drugs is not well understood. This study reports the use of differential scanning calorimetry (DSC) to measure the solubility of methylphenidate both as the free base and as the hydrochloride salt in two polymethacrylate copolymers, Eudragit RS (EuRS) and Eudragit E (EuE) and relates this to the ability of films formed using these polymers to deliver methylphenidate across a model membrane. EuRS provided greater methylphenidate delivery when the drug was formulated as the free base in comparison EuE because the lower solubility of the drug in EuRS provided a higher degree of drug saturation in the polymeric film. In contrast EuE provided greater delivery of methylphenidate hydrochloride as EuRS could not prevent its crystallisation from a supersaturated state. Methylphenidate flux across the membrane could be directly related to degree of saturation of the drug in the film formulation as estimated by the drug solubility in the individual polymers demonstrating the importance of drug solubility in the polymer included in film forming systems for topical/transdermal drug delivery. In addition DSC has been demonstrated to be a useful tool for determining the solubility of drugs in polymers used in film forming systems and the approaches outlined here are likely to be useful for predicting the suitability of polymers for particular drugs in film forming transdermal drug delivery systems.

IMPORTANCE: Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear. OBJECTIVE: To investigate the association between methylphenidate and the risk of suicide attempts. DESIGN, SETTING, AND PARTICIPANTS: A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients. MAIN OUTCOMES AND MEASURES: Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods. RESULTS: Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35). CONCLUSIONS AND RELEVANCE: The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts., link_to_OA_fulltext

A presente pesquisa de campo refere-se ao uso indiscriminado de psicoestimulantes, com ênfase no cloridrato de metilfenidato. Este medicamento é indicado para o tratamento do Transtorno de Déficit de Atenção e Hiperatividade (TDAH) e da narcolepsia. O cloridrato de metilfenidato é um fármaco que age no sistema nervoso central, inibindo a recaptação de dopamina e noradrenalina dos terminais sinápticos. Ele vem sendo usado, sem a orientação medica, de forma a potencializar as funções cognitivas de indivíduos que não possuem nenhum tipo de distúrbio. O objetivo desta pesquisa foi identificar e quantificar o uso não terapêutico do cloridrato de metilfenidato, analisar os efeitos colaterais provocados por tal medicamento e fazer um levantamento do uso de outros psicoestimulantes. A pesquisa foi realizada na Faculdade Anhanguera de Brasília (FAB), com a aplicação de um questionário sobre o uso indiscriminado do cloridrato de metilfenidato ou outros psicoestimulantes pelos estudantes dos cursos de Biomedicina, Enfermagem, Farmácia e Nutrição. A análise dos dados coletados demonstrou que, de um total de 400 entrevistados, 6,0% (n=24) relataram o uso de metilfenidato. Dentre os estudantes que relataram o uso, somente 16,7% (n=4) possuíam o diagnóstico médico de TDAH para o uso terapêutico. Outros autores apontam um aumento crescente na produção e na utilização do cloridrato de metilfenidato. De acordo com a avaliação do questionário respondido pelos alunos da FAB 19,5% dos estudantes revelaram já terem feito uso de algum medicamento para auxiliar os estudos e 57% dos alunos que usaram o cloridrato de metilfenidato como psicoestimulantes o fizeram sem a orientação de um médico.

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Due to lack of response to the medication and significant side effects of the treatment with stimulants, alternative medications should be considered. The aim of this study is to evaluate efficacy of agomelatine in treatment of ADHD.Fifty-four outpatients, children 6-15 years old, with diagnosis of ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria participated in a 6-week, parallel, double-blind, randomized clinical trial. Fifty patients completed 6 weeks of treatment with either ritalin (methylphenidate hydrochloride [MPH]) (20 mg/day in participants below 30 kg and 30 mg/day in patients with weight ≥30 kg) or agomelatine (15 mg/day in patients with weight ≥30 kg and 25 mg/day in patients with weight ≥45 kg). Participants were assessed using Parent and Teacher ADHD Rating Scale-IV at baseline and at weeks 3 and 6.General linear model repeated measures showed no significant differences between the two groups on Parent and Teacher Rating Scale scores (F = 1.13, df = 1.26, p = 0.305, and F = 0.95, df = 1.25, p = 0.353, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the agomelatine group (9.28 ± 8.72 and 24.12 ± 7.04, respectively) and the MPH group (6.64 ± 11.04 and 25.76 ± 7.82, respectively) (p = 0.46 and p = 0.44, respectively). There was a trend for less insomnia in the agomelatine group versus MPH-treated group (4% vs. 24%, p = 0.09).A treatment course of 6 weeks with agomelatine demonstrated a favorable safety and efficacy profile in children and adolescents with ADHD. Nonetheless, larger controlled studies with longer treatment periods are necessary.

Summary This study sought to: (1) compare actigraphy-derived estimated sleep variables to the same variables based on the gold-standard of sleep assessment, polysomnography; (2) examine whether the correlations between the measures differ between children with attention-deficit/hyperactivity disorder and typically developing children; and (3) determine whether these correlations are altered when children with attention-deficit/hyperactivity disorder are treated with medication. Participants (24 attention-deficit/hyperactivity disorder; 24 typically developing), aged 6–12 years, completed a 1-week baseline assessment of typical sleep and daytime functioning. Following the baseline week, participants in the attention-deficit/hyperactivity disorder group completed a 4-week blinded randomized control trial of methylphenidate hydrochloride, including a 2-week placebo and 2-week methylphenidate hydrochloride treatment period. At the end of each observation (typically developing: baseline; attention-deficit/hyperactivity disorder: baseline, placebo and methylphenidate hydrochloride treatment), all participants were invited to a sleep research laboratory, where overnight polysomnography and actigraphy were recorded concurrently. Findings from intra-class correlations and Bland–Altman plots were consistent. Actigraphy was found to provide good estimates (e.g. intra-class correlations >0.61) of polysomnography results for sleep duration for all groups and conditions, as well as for sleep-onset latency and sleep efficiency for the typically developing group and attention-deficit/hyperactivity disorder group while on medication, but not for the attention-deficit/hyperactivity disorder group during baseline or placebo. Based on the Bland–Altman plots, actigraphy tended to underestimate for sleep duration (8.6–18.5 min), sleep efficiency (5.6–9.3%) and sleep-onset latency, except for attention-deficit/hyperactivity disorder during placebo in which actigraphy overestimated (−2.1 to 6.3 min). The results of the current study highlight the importance of utilizing a multimodal approach to sleep assessment in children with attention-deficit/hyperactivity disorder.

Purpose A novel methylphenidate hydrochloride extended-release chewable tablet (MPH ERCT) was developed to potentially address an unmet need for patients with attention-deficit/hyperactivity disorder, especially children, who cannot or will not swallow tablets or would prefer the convenience of a chewable tablet. This randomized, open-label, crossover trial compared the pharmacokinetic properties and relative bioavailability of MPH ERCT with an MPH chewable immediate-release tablet (IR MPH) formulation in healthy adults. Methods Healthy men and women 18 to 55 years of age were randomly assigned to MPH ERCT 40 mg or 40 mg IR MPH administered in 2 equal doses of 20 mg 6 hours apart with a 7-day washout period. Plasma concentrations of MPH at selected time points up to 24 hours were measured, and pharmacokinetic parameters were determined using a noncompartmental approach in the SAS (Version 9.2) PROC general linear model procedure. Findings A total of 33 participants were enrolled in the study; 31 participants were included in the pharmacokinetic analysis. The exposure ratios for MPH ERCT and IR MPH (MPH ERCT/IR MPH) for area under the analyte concentration versus time curves (AUC) from time zero to the last measurable analyte concentration (AUC 0–last ) (87.64%; 95% CI, 84.96–90.41) and AUC 0–∞ (89.11%; 95% CI, 86.57–91.73) were within the standard 80% to 125% bioequivalence acceptance criteria. Mean C max for MPH ERCT and IR MPH was 12.51 ng/mL and 15.57 ng/mL, respectively; mean time to C max was 4.16 hours and 6.43 hours, respectively. The mean C max of MPH ERCT was 80% of the C max of IR MPH due to a higher peak concentration that occurs after the second dose of IR MPH. All adverse events were mild in severity. Implications The relative bioavailability of MPH ERCT 40 mg, based on the exposure (AUC), was comparable to that of IR MPH 40 mg administered in 2 equal doses of 20 mg 6 hours apart. Both formulations were generally well tolerated.

IMPORTANCE\nAlthough numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system.\nOBJECTIVES\nTo determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function.\nDESIGN, SETTING, AND PARTICIPANTS\nA randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment-naive status.\nINTERVENTIONS\nTreatment with either methylphenidate or a matched placebo for 16 weeks.\nMAIN OUTCOMES AND MEASURES\nChange in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses.\nRESULTS\nAmong 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03).\nCONCLUSIONS AND RELEVANCE\nWe confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up.\nTRIAL REGISTRATION\nidentifier: NL34509.000.10 and trialregister.nl identifier: NTR3103.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common behavioural disorder in childhood. The psychostimulant methylphenidate hydrochloride (MPH) is one of the major pharmacological options for ADHD. MPH is known to result, on average, in a small increase in arterial blood pressure (BP). However, there are few clinical data regarding theindividualinfluences of MPH on BP among children and adolescents with ADHD. According to the European Union-wide standardised patient information sheet for MPH, BP changes >10 mm Hg compared with baseline values are ‘common’ (ie, ≥1% to AimTo investigate the frequency and individual severity of BP changes in children and adolescents with ADHD during the first 6 months of new MPH therapy.MethodsIn this study, 44 (77% male) children and adolescents (mean age (SD) 9.13 (1.86) years) with a diagnosis of ADHD according to the International Classification of Diseases, tenth revision, underwent ambulatory BP monitoring before and during the first 6 months of routine MPH therapy. Exclusion criteria were pre-existing MPH therapy and other medications that potentially influence BP or interfere with MPH. The non-interventional study was conducted prospectively at 10 paediatric cardiology centres in Germany and Austria.ResultsAfter beginning MPH therapy, 34% of participants (99% CI 15.52% to 52.66%) had BP increases/decreases >10 mm Hg. The mean changes in systolic BP and diastolic BP were 0.87 mm Hg (95% CI -1.75 mm Hg to 3.48 mm Hg) and 1.96 mm Hg (95% CI 0.21 mm Hg to 3.7 mm Hg), respectively. The proportion of participants with initial prehypertension/hypertension was 54.55% .ConclusionsIn our sample with a high baseline rate of prehypertension/hypertension, BP changes >10 mm Hg during MPH therapy were more frequent than those indicated by the patient information sheet. Moreover, individual BP changes, including increases and decreases >10 mm Hg, resulted in a small average BP increase in the sample, thus reflecting neither the severity nor the direction of individual BP changes. Therefore, the frequency and, due to the common use of the arithmetic mean, the individual severity of BP changes during MPH therapy may be underestimated. Further studies without averaging and with larger samples including patients in primary care settings are warranted.

O artigo discute a promoção de resiliência a partir da análise das significações produzidas no contexto de alunos diagnosticados com Transtorno de Déficit de Atenção e Hiperatividade (TDAH) que fazem uso do Cloridrato de Metilfenidato. O modelo Bioecológico do Desenvolvimento Humano foi adotado como aporte teórico-metodológico. A pesquisa optou pela abordagem qualitativa de cunho descritivo-interpretativo e contou com a participação de 40 pessoas, a saber: profissionais da saúde (1 neuropediatra, 1 psicólogo); profissionais da educação (5 pedagogos, 11 professores); 10 alunos e 12 familiares. Os dados foram coletados mediante entrevista no contexto de seis escolas municipais de uma cidade norte-paranaense. Os resultados indicaram a necessidade de repensar as práticas avaliativas correntes e revelaram que o processo diagnóstico é demarcado por fatores de risco e de proteção, os quais afetam o processo de aprendizagem escolar. Os dados permitiram inferir que a promoção da resiliência, nesta situação, pode resultar no estabelecimento de redes protetivas, maior inter-relação entre os profissionais de saúde e educação e suporte efetivo aos familiares e alunos usuários do medicamento. Esse contexto resultaria em condições mais favoráveis à vinculação do aluno à escola e a mudanças positivas no processo de aprendizagem escolar dos alunos diagnosticados com TDAH.