The effect of methylphenidate for giggle incontinence in children.

INTRODUCTION: Giggle incontinence (GI) is a rare form of urinary incontinence that occurs during or immediately after laughing due to involuntary and complete bladder emptying. Few studies in the literature report that methylphenidate can be effective in treatment of this condition. OBJECTIVE: The aim of this study is to characterize children with GI and evaluate their response to methylphenidate, as well as describe treatment duration, dosage of methylphenidate, relapse rates after discontinuation of medication, and side effects. METHODS: Medical records and 48-h frequency-volume charts from children treated with methylphenidate for GI in the period January 2011-July 2021 were retrospectively analyzed. RESULTS: Eighteen children were diagnosed with GI and fulfilled inclusion criteria. Fifteen patients were included in analysis, as 3 out of 18 children decided not to take the methylphenidate that was prescribed. In total, 14 out of the 15 GI patients treated with methylphenidate experienced clinical effect. All patients included in the study had methylphenidate prescribed in a dose range of 5-20 mg daily. Treatment duration ranged from 30 to 1001 days, with a median of 152 days (IQR 114, 243.5). Ten children experienced complete response and two of those reported symptom relapse after discontinuation of the methylphenidate. Only mild and short-lasting side effects were reported by two patients. DISCUSSION: Our study demonstrates that methylphenidate is an effective treatment in children diagnosed with GI. Side effects are mild and uncommon.

Consumo de psicoestimulantes por estudantes de medicina em um centro universitário privado / Consumption of psychostimulants by medical students in a private university center

O consumo de psicoestimulantes tem crescido exponencialmente, sobretudo entre estudantes de medicina, na busca por aumentar o rendimento acadêmico. Atualmente, a extensa carga horária de aulas e estudos, exigências de produtividade e altos níveis de estresse podem desencadear o uso. Objetivo: Analisar o uso de psicoestimulantes por estudantes do curso de Medicina de um Centro Universitário privado em Minas Gerais. Métodos: Foi realizado um estudo descritivo, quantitativo, com delineamento transversal entre os discentes do 1° ao 5° ano do curso de Medicina no 2° semestre de 2021. Os participantes responderam ao questionário semi-estruturado elaborado pelos autores. Os dados obtidos foram tabulados no software Statistical Product and Service Solutions. Resultados: Dos 244 entrevistados, cerca de 57.4% faziam uso de algum psicoestimulante. Houve maior uso entre os estudantes do 2° ano e as principais substâncias utilizadas foram: cafeína (85%), energético (65%) e metilfenidato (60%). A melhora na concentração (97%) foi o efeito mais percebido pelos usuários, seguido de redução do sono (83%) e melhora de raciocínio (80%). Muitos consideraram que os estimulantes cerebrais têm o potencial de melhorar o rendimento acadêmico, mas pode reduzir a qualidade do sono e consequentemente torná-los susceptíveis a outras enfermidades. Conclusão: É notável que existe uso abusivo de estimulantes cerebrais, sendo fundamental o trabalho em conjunto entre instituição de ensino e familiares, em prol da prevenção e do controle de danos causados por esse hábito

The consumption of psychostimulants has grown exponentially, especially among medical students, in the quest to increase academic performance. Currently, the extensive workload of classes and studies, productivity demands and high levels of stress can trigger use. Objective: To analyze the use of psychostimulants by medical students at a private University Center in Minas Gerais. Methods: A descriptive, quantitative, cross-sectional study was carried out among students from the 1st to the 5th year of the medicine course in the 2nd semester of 2021. The participants answered the semi-structured questionnaire prepared by the authors. The data obtained were tabulated in the Statistical Product and Service Solutions software. Results: Of the 244 respondents, about 57.4% used some psychostimulant. There was greater use among 2nd year students and the main substances used were: caffeine (85%), energy drink (65%) and methylphenidate (60%). Improved concentration (97%) was the effect most perceived by users, followed by reduced sleep (83%) and improved thinking (80%). Many considered that brain stimulants have the potential to improve academic performance, but can reduce sleep quality and consequently make them susceptible to other illnesses. Conclusion: It is notable that there is abusive use of brain stimulants, and it is essential to work together between educational institutions and family members in order to prevent and control the damage caused by this habit

The effect of Rosa canina L. and a polyherbal formulation syrup in patients with attention-deficit/hyperactivity disorder: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is the most common behavioral disorder in childhood and adolescence. A number of these patients do not respond to the current pharmacological treatments and there may also be drug side effects. This study aims to determine the efficacy and safety of two herbal medicine products, including Rosa canina L. (RC) and a polyherbal formulation (PHF) syrup, on the clinical manifestations of ADHD in children and adolescents. METHODS: Ninety ADHD patients based on DSM-5 diagnostic criteria will be randomly assigned equally into three groups: (1) RC syrup + methylphenidate (MP), (2) PHF syrup + MP, and (3) placebo + MP according to the inclusion criteria (30 subjects in each group). The syrup dosage is 5cc every 8 h, and MP will have a stabilized dose for 8 weeks during the study. Moreover, Conner's questionnaires will be completed by the teacher and parents before the intervention and then every 4 weeks. Also, the Child Symptom Inventory-fourth edition (CSI-4) and temperament questionnaires will be completed before the intervention and every 4 weeks until 2 months. DISCUSSION: This trial is the first experiment to determine the effects of RC and PHF syrups on the clinical manifestations of ADHD in children and adolescents. Our findings provide new insight into the effect of these herbal products on the clinical manifestations of ADHD. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20190923044855N1 . Registered on 14 January 2020. The trial was registered at https://www.irct.ir/ .

Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. OBJECTIVES: To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. SEARCH METHODS: In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. MAIN RESULTS: We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. AUTHORS' CONCLUSIONS: We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.

Effects of curcumin nanoparticle on the histological changes and apoptotic factors expression in testis tissue after methylphenidate administration in rats.

The present article sought to evaluate the impact of curcumin-loaded superparamagnetic iron oxide (Fe3O4) nanoparticles (NPs) on the histological variables and apoptotic agents in adult male rats after 3-weeks of methylphenidate (MPH) oral administration (20 mg/kg) versus vehicle therapy on the testis. Twenty-four male rats have been categorized randomly into four groups, in which Group 1 has been chosen as the controls, and Group 2 has been a vehicle and taken the sesame oil as curcumin carrier. Moreover, Group 3 has been taken MPH (20 mg/kg by gavage for 21 consecutive days). Group 4 received MPH plus Curcumin nanoparticles (5.4 mg/100 g) for twenty-one consecutive days. Then, testis histology, apoptosis as well as stereology have been examined. According to the examinations, curcumin nanoparticles are significantly capable of improving the sperms and stereological variables; for example, round spermatid and Leydig cells by enhancing the level of the serum testosterone in comparison with the MPH and vehicle groups. Besides, it was found that the gene expression in inflammation pathways and apoptosis genes largely diminished in the treatment group by curcumin nanoparticles in comparison with the MPH and vehicle groups, also we observed considerable differences for the weight of testes between the examined groups. Therefore, Curcumin effectively inhibited the testis damages and MPH-induced apoptosis, indicating possible protecting features of the Curcumin nanoparticles in opposition to MPH.

Natural Health Product-Drug Interaction Causality Assessment in Pediatric Adverse Event Reports Associated with Attention-Deficit/Hyperactivity Disorder Medication.

Background: Some pediatric patients with attention-deficit/hyperactivity disorder (ADHD) use natural health products (NHPs) such as herbal remedies. Although herbal remedies are generally considered to be safe when they are used appropriately, they may contain active components that can interact with medications being used concurrently, with potential for NHP-drug interactions leading to adverse events. Objectives: The objectives of this study were (1) to identify adverse event reports (AERs) involving commonly used herbal remedies and ADHD prescription medicines in children and adolescents; (2) to evaluate the quality of collected AERs; and (3) to assess whether NHP-drug interactions can be causally linked to reported adverse events. Methods: We systematically searched the FDAble database (FDAble.com) for herbal remedies commonly used by patients (4-18 years old) also taking ADHD drugs from 1997 to 2015. We assessed the completeness of the AERs and used three causality assessment tools modified for NHPs (Naranjo Adverse Drug Reaction Probability Scale, HORN Drug Interaction Probability Scale, and World Health Organization Uppsala Monitoring Centre Scale). Results: Of the 23 identified AERs involving both an herbal remedy and an ADHD prescription medication, most involved multiple (>3) substances with inadequate detail to assess multiple potential interactions. Following data extraction and evaluation of completeness, five AERs involving only one herbal remedy and one ADHD medication were evaluated for causality. An NHP-drug interaction was assessed to be probable in one case and to be possible in another. Both these reports involved a methylphenidate formulation and St. John's wort. Conclusions: Eighteen of the 23 identified AERs involving both an herbal remedy and an ADHD drug also involved other multiple ingredient products. The reporting quality was poor for the five AERs examined. Further research is needed to study the interaction between St. John's wort and methylphenidate.

Treatment for Gulf War Illness (GWI) with KPAX002 (methylphenidate hydrochloride + GWI nutrient formula) in subjects meeting the Kansas case definition: A prospective, open-label trial.

This study tested the safety, tolerability, and efficacy of KPAX002-a combination of methylphenidate hydrochloride plus a micronutrient formula designed to support mitochondrial function-as a treatment for Gulf War Illness (GWI). This open-label trial enrolled 17 subjects meeting the Kansas case definition for GWI. Of the 17 subjects enrolled, 15 qualified for the Intent-to-Treat (ITT) population with 10 subjects completing the trial per protocol. All analyses were on the ITT population. At 12 weeks, subjects taking KPAX002 experienced a mean 25% reduction in their overall GWI symptoms severity as measured by the GWI Symptoms Assessment Tool (SAT) (p < 0.001). Visual analog scale scores were also significantly reduced for fatigue (p = 0.019), cognitive symptoms (p = 0.006), sleep problems (p = 0.026), and pain (p = 0.05). Twelve weeks of KPAX002 administration resulted in a significant improvement in GWI symptoms with an acceptable side effect profile. A larger randomized, double-blinded, placebo-controlled trial is necessary to determine if the observed benefit can be replicated.

Efficacy and safety of tipepidine as adjunctive therapy in children with attention-deficit/hyperactivity disorder: Randomized, double-blind, placebo-controlled clinical trial.

AIM: This study evaluated the efficacy and safety of tipepidine as an add-on to methylphenidate in the drug treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: This study was an 8-week, randomized, parallel group, double-blind, placebo-controlled trial recruiting 53 ADHD-diagnosed children. Patients were randomly divided to receive methylphenidate + tipepidine or methylphenidate + placebo for 8 weeks. Participants were assessed using the parent version of ADHD Rating Scale-IV and the Clinical Global Impression scale at baseline, at week 4, and at the end of the trial. Moreover, the safety and tolerability of the treatment strategies were compared. RESULTS: On general linear model repeated measures analysis a significant effect was seen for time × treatment interaction on the total and hyperactivity-impulsivity subscales of the Parent ADHD Rating Scale-IV during the trial period (Greenhouse-Geisser corrected: F = 3.45, d.f. = 1.52, P = 0.049, and F = 5.17, d.f. = 1.52, P = 0.014, respectively). The effect for time × treatment interaction, however, was not significant on Clinical Global Impression-Severity scale (Greenhouse-Geisser corrected: F = 1.79, d.f. = 1.43, P = 0.182). The frequencies of adverse events were similar between the two groups. CONCLUSION: Eight weeks of treatment with tipepidine, as a supplementary medication, resulted in satisfactory efficacy and safety of the adjuvant therapy in management of patients with ADHD. Rigorous investigations, however, involving larger sample sizes, more extended treatment periods, and dose responses should be considered.

Early monitoring of fatty acid profile in children with attention deficit and/or hyperactivity disorder under treatment with omega-3 polyunsaturated fatty acids.

BACKGROUND: Cognitive effects of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) might make them helpful in attention deficit/hyperactivity disorder (ADHD). However, the results derived from supplementation studies in children depend on the respective combinations and the study period. We aimed to investigate the serum fatty acid profile, attention scores and the tolerability in a group of ADHD children after receiving methylphenidate (MPH) and ω-3 PUFAs for 1 month. METHODS: A combination of MPH (1 mg/kg/day) and eicosapentaenoic (EPA, 70 mg/day) + docosahexaenoic acids (DHA, 250 mg/day) was administered to 40 ADHD children (7-15 years). An analysis of serum fatty acids by gas chromatography and an assessment of attention by using the Magallanes Scale of Visual Attention (MSVA) were carried out before and after 1 month of treatment. RESULTS: Our data revealed significant decreases of several ω-6 PUFAs, like arachidonic acid (P<0.0259). EPA and DHA concentrations increased by 27% and 3% respectively, and the ω-6/ω-3 index slightly decreased. The quality of attention significantly increased (P<0.026) and an improvement of ADHD core symptoms was reported both by parents and by teachers. No severe side effects occurred. CONCLUSIONS: Results demonstrate that the combination of MPH and EPA+DHA at the tested doses has positive clinical effects and an adequate safety profile. Therefore, our study suggests that ω-3 PUFAs may represent a feasible and a safe adjuvant therapy in children with ADHD and might enhance the effects of MPH. Further long-term follow-up studies are required to confirm these initial findings.

Effect of vitamin D supplementation as adjunctive therapy to methylphenidate on ADHD symptoms: A randomized, double blind, placebo-controlled trial.

OBJECTIVES: Previous studies have shown that serum levels of vitamin D were lower in attention deficit hyperactivity disorder (ADHD) children compared to healthy controls. The aim of the study was to determine the effect of vitamin D supplementation as adjunctive therapy to methylphenidate on symptoms of children with ADHD. METHODS: Sixty-two children aged 5-12 years with a diagnosis of ADHD based on DSM-IV criteria were randomly assigned into two groups to receive either 2000IU vitamin D or placebo in addition to methylphenidate for 8 weeks. Symptoms severity was assessed by Conner's Parent Rating Scale-Revised[S] (CPRS), ADHD rating scale-IV (ADHD-RS), and Weekly Parent Ratings of Evening and Morning Behavior (WPREMB) at weeks 0, 4, and 8. Serum levels of 25(OH)D were measured at baseline and after 8 weeks. Anthropometric variables, dietary intake, physical activity, sun exposure, and side effects were assessed. RESULTS: Fifty-four participants completed the trial. After 8 weeks of supplementation, serum levels of 25(OH)D significantly increased in the vitamin D group. ADHD symptoms decreased significantly in both groups (P < 0.05). Evening symptoms and total score of WPREMB scale were significantly different at weeks 4 and 8 between the two groups (P = 0.013, 0.016, respectively), but no differences were found in symptoms by CPRS and ADHD-RS scales. DISCUSSION: Vitamin D supplementation as adjunctive therapy to methylphenidate improved ADHD evening symptoms. Future research is needed to clarify vitamin D effects as monotherapy in ADHD and its mechanism. The trial was registered in www.irct.ir is (IRCT201404222394N10).

Effect of Pycnogenol® on attention-deficit hyperactivity disorder (ADHD): study protocol for a randomised controlled trial.

BACKGROUND: Methylphenidate (MPH), the first choice medication for attention-deficit hyperactivity disorder (ADHD), is associated with serious adverse effects like arrhythmia. Evidence on the association of ADHD with immune and oxidant-antioxidant imbalances offers potential for antioxidant and/or immunomodulatory nutritional supplements as ADHD therapy. One small randomised trial in ADHD suggests, despite various limitations, therapeutic benefit from Pycnogenol®, a herbal, polyphenol-rich extract. METHODS: This phase III trial is a 10-week, randomised, double-blind, placebo and active treatment controlled multicentre trial with three parallel treatment arms to compare the effect of Pycnogenol® to MPH and placebo on the behaviour of 144 paediatric ADHD and attention-deficit disorder (ADD) patients. Evaluations of behaviour (measured by the ADHD-Rating Scale (primary endpoint) and the Social-emotional Questionnaire (SEQ)), immunity (plasma cytokine and antibody levels, white blood cell counts and faecal microbial composition), oxidative stress (erythrocyte glutathione, plasma lipid-soluble vitamins and malondialdehyde and urinary 8-OHdG levels, as well as antioxidant enzyme activity and gene expression), serum zinc and neuropeptide Y level, urinary catecholamines and physical complaints (Physical Complaints Questionnaire) will be performed in week 10 and compared to baseline. Acceptability evaluations will be based on adherence, dropouts and reports of adverse events. Dietary habits will be taken into account. DISCUSSION: This trial takes into account comorbid behavioural and physical symptoms, as well as a broad range of innovative immune and oxidative biomarkers, expected to provide fundamental knowledge on ADHD aetiology and therapy. Research on microbiota in ADHD is novel. Moreover, the active control arm is rather unseen in research on nutritional supplements, but of great importance, as patients and parents are often concerned with the side effects of MPH. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT02700685 . Registered on 18 January 2016. EudraCT 2016-000215-32 . Registered on 4 October 2016.

Uso do metilfenidato na medicalização da educação infantil: revisão integrativa / Use of imethylphenidate n medicalization of childhood education: integrative review / El uso de metilfenidato en la medicalización de la educación infantil: revisión integrativa

Objetivo: analisar o que versam as produções científicas sobre o uso do Metilfenidato na medicalização da educação infantil, vinculando-as com aspectos éticos, bioéticos e legais. Método: revisão integrativa realizada nas bases de dados Lilacs, Medline, Index Psicologia, biblioteca virtual ScIELO e pela ferramenta de pesquisa Google Acadêmico. A busca resultou no encontro de quarenta e nove estudos, após aplicação dos critérios de seleção, a amostra compôs-se de oito artigos. Resultados: verificou-se que apesar de nenhum estudo relacionar diretamente o uso do Metilfenidato com a bioética, vários destes, suscitaram considerações de que essa prática pode representar malefício ao desenvolvimento infantil e transgressão a princípios legais. Conclusão: os critérios utilizados na prescrição do Metilfenidato para crianças devem ser mais rigorosos, pois, ao submetê-las aos efeitos do fármaco, profissionais da saúde, familiares e educadores, poderão estar violando princípios éticos, bioéticos e legais.(AU)

Objective: to analyze the scientific productions that deal on the use of methylphenidate in the medicalization of childhood education, linking them with ethical, bioethical and legal aspects. Method: this is an integrative review carried out in the databases Lilacs, Medline, Index Psicologia, virtual library SciELO and the search tool Google Scholar. The search resulted in the meeting of forty-nine studies, after applying the selection criteria, the sample consisted of eight articles. Results: it was found that although there aren't any studies directly related to the use of methylphenidate with bioethics, several of these ones raised considerations that this practice can pose harm to children's development and breach of legal principles. Conclusion: the criteria used in the prescription of methylphenidate for children should be more stringent because, by subjecting them to drug effects, health professionals, family members and educators may be violating ethical, bioethical and legal principles.(AU)

Objetivo: analizar las producciones científicas que tratan sobre el uso de metilfenidato en la medicalización de la educación infantil, vinculándolos con aspectos éticos, bioéticos y legales. Método: se trata de una revisión integradora llevada a cabo en las bases de datos LILACS, MEDLINE, Índice de Psicología, biblioteca virtual SciELO y una herramienta de búsqueda de Google Scholar. La búsqueda dio como resultado la reunión de cuarenta y nueve estudios, después de aplicar los criterios de selección, la muestra consistió en ocho artículos. Resultados: se encontró que aunque no hay estudios relacionan directamente con el uso de metilfenidato bioética, varias de ellas, las consideraciones que esta práctica puede suponer un daño para el desarrollo y la violación de los principios legales de los niños levantó. Conclusión: los criterios utilizados en la prescripción de metilfenidato para los niños debe ser más estrictos, ya que, al someterlos a efectos de los medicamentos, los profesionales de la salud, parientes y educadores puedan estar violando principios éticos, bioéticos y legales.(AU)

Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustained-release formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained- release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.

Sudden hearing loss associated with methylphenidate therapy.

An 8-year-old child diagnosed with attention deficit/hyperactivity disorder presented to our Department of Otolaryngology 4 days after suffering hearing loss, loss of balance, tinnitus, and fullness sensation of the left ear. Her symptoms occured with the first dose of methylphenidate. The medical history and physical examination revealed no other diseases associated with sudden hearing loss. The audiogram revealed a total hearing loss on the left ear. Stapedial reflexes, distortion product and transient-evoked otoacoustic emissions were absent in left ear. The absence of clinical, laboratory and radiological evidence of a possible cause for complaints, an association between methylphenidate and sudden hearing loss was suggested. The patient received a standard course of oral corticosteroid and hyperbaric oxygen therapy. Weekly otological and audiological examinations were performed. Conservative and medical treatments offered no relief from hearing loss. Sudden hearing loss is a serious and irreversible adverse effect of methylphenidate. Therefore, the risk of hearing loss should be taken into consideration when initiating methylphenidate therapy.

Methylphenidate-induced acute orofacial and extremity dyskinesia.

Methylphenidate is a short-acting stimulant. In this article, the authors report a 7-year-old male patient who presented with orofacial and limb dyskinesia after his first dose of methylphenidate treatment for a diagnosis of attention-deficit/hyperactivity disorder; he was also receiving sodium valproate treatment for epilepsy. Orofacial dyskinesia appeared 5 hours after methylphenidate administration, persisted for 10 hours, and had completely resolved within 2 days. Although limb dyskinesia after methylphenidate is a commonly reported side effect, to the authors' knowledge this is only the second reported case to develop both orofacial and limb dyskinesia in the acute period after the first dose of methylphenidate. This case is reported to emphasize the potential side effects of methylphenidate, individual differences in drug sensitivities, and drug-receptor interactions via different mechanisms.

Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies.

There is evidence from animal studies that repeated exposure to methylphenidate (MPH), a widely used psychostimulant for the treatment of attention deficit hyperactivity disorder (ADHD), produces behavioural, structural and neurochemical changes that persist long after drug administration has ended. However, the translational utility of much of this work is compromised by the use of drug doses and routes of administration that produce plasma and brain MPH levels that fall outside the clinical range, i.e. experimental parameters more relevant to drug abuse than ADHD. We used PubMed to identify pre-clinical studies that employed repeated MPH administration at low doses in young rodents and examined long-term effects on cognition, emotion, and brain structure and function. A review of this work suggests that repeated MPH treatment during early development can modify a number of cognitive, behavioural and brain processes, but these are reduced when low therapeutic doses are employed. Moreover, MPH sites of action extend beyond those implicated in ADHD. Studies that combined neurobiological and behavioural approaches provide important insights into the mechanisms underlying MPH-produced effects on cognitive and behavioural processes, which may be relevant to MPH therapeutic efficacy. There is an emerging consensus that pharmacological treatment of childhood psychiatric disorders produces persistent neuroadaptations, highlighting the need for studies that assess long-term effects of early developmental pharmacotherapy. In this regard, studies that mimic clinical therapy with rodents are useful experimental approaches for defining the behavioural and neural plasticity associated with stimulant therapy in paediatric populations.

Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention-deficit/hyperactivity disorder.

OBJECTIVE: Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non-substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. METHOD: Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13-18) with at least one non-nicotine SUD and one with 255 adult smokers (18-55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). RESULTS: Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. CONCLUSIONS: With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence.

A hidden Markov model to assess drug-induced sleep fragmentation in the telemetered rat.

Drug-induced sleep fragmentation can cause sleep disturbances either via their intended pharmacological action or as a side effect. Examples of disturbances include excessive daytime sleepiness, insomnia and nightmares. Developing drugs without these side effects requires insight into the mechanisms leading to sleep disturbance. The characterization of the circadian sleep pattern by EEG following drug exposure has improved our understanding of these mechanisms and their translatability across species. The EEG shows frequent transitions between specific sleep states leading to multiple correlated sojourns in these states. We have developed a Markov model to consider the high correlation in the data and quantitatively compared sleep disturbance in telemetered rats induced by methylphenidate, which is known to disturb sleep, and of a new chemical entity (NCE). It was assumed that these drugs could either accelerate or decelerate the transitions between the sleep states. The difference in sleep disturbance of methylphenidate and the NCE were quantitated and different mechanisms of action on rebound sleep were identified. The estimated effect showed that both compounds induce sleep fragmentation with methylphenidate being fivefold more potent compared to the NCE.

Nutrición y trastorno por déficit de atención/hiperactividad: seguimiento evolutivo de las variables antropométricas de un grupo de pacientes en tratamiento con metilfenidato de liberación osmótica / Nutrition and attention deficit hyperactivity disorder: developmental follow-up of the anthropometric variables of a group of patients receiving treatment with osmotic controlled-release methylphenidate

Objetivo. Realizar un análisis evolutivo de las variables antropométricas de un grupo de pacientes diagnosticados de trastorno por déficit de atención/hiperactividad (TDAH) para determinar la repercusión del tratamiento con metilfenidato de liberación osmótica (MTF-OROS). Pacientes y métodos. Se han revisado retrospectivamente las historias clínicas de 187 pacientes con TDAH en tratamiento con MTF-OROS durante 30 meses, registrándose los pesos y tallas e índice de masa corporal al diagnóstico (basal) y a los 6, 12, 18, 24 y 30 meses de seguimiento. Resultados. La edad media al diagnóstico era de 8,14 ± 1,6 años. La dosis de MTF-OROS fue incrementándose progresivamente hasta 36,9 ± 12,1 mg/día (1,05 mg/kg/día) a los 30 meses del seguimiento. Al diagnóstico, el 34,9% de los pacientes tenía una situación nutricional deficiente (subnutrición o malnutrición), que a los 30 meses de tratamiento afectaba al 50,3% de los pacientes. El valor basal del peso (Z-score) disminuía progresivamente durante el tratamiento, llegando a alcanzar unos valores significativamente inferiores (p < 0,05) respecto al valor basal a los 12 meses, y se mantenía significativamente inferior hasta los 30 meses. El valor basal de la talla (Z-score) también disminuía progresivamente durante el tratamiento, llegando a alcanzar unos valores significativamente inferiores (p < 0,05) respecto al valor basal a los 24 y 30 meses. Conclusiones. En el momento del diagnóstico de TDAH, uno de cada tres pacientes se hallaba en una situación nutricional deficiente (subnutrición o malnutrición). El tratamiento continuado con MTF-OROS durante 30 meses ejerce una influencia negativa sobre la talla, que posiblemente podría atenuarse mejorando la nutrición de los pacientes (AU)

Aim. To perform a developmental analysis of the anthropometric variables of a group of patients diagnosed with attention deficit hyperactivity disorder (ADHD) in order to determine the repercussions of treatment with osmotic controlled-release methylphenidate (MTF-OROS). Patients and methods. The medical records of 187 patients with ADHD under treatment with MTF-OROS over a period of 30 months were reviewed. Data collected included weight, height and body mass index at diagnosis (baseline) and at 6, 12, 18, 24 and 30 months’ follow-up. Results. The mean age at diagnosis was 8.14 ± 1.6 years. The dose of MTF-OROS was progressively increased until 36.9 ± 12.1 mg/day (1.05 mg/kg/day) at day 30 of the follow-up. At diagnosis, 34.9% of patients had a deficient nutritional situation (subnutrition or malnutrition), which affected 50.3% of the patients at 30 months. The baseline value for weight (Z-score) progressively decreased during treatment until values that were significantly lower than the baseline value at 12 months were reached (p < 0.05); these values remained significantly lower until 30 months. The baseline value for height (Z-score) also progressively decreased during treatment until values that were significantly lower than the baseline value at 24 and 30 months were reached (p < 0.05). Conclusions. At the time they were diagnosed with ADHD, one out of every three patients was in a deficient nutritional situation (subnutrition or malnutrition). Continued treatment with MTF-OROS for 30 months had a negative influence on height, which could perhaps be attenuated by improving the patients’ nutrition (AU)