Stimulant prodrugs: A pharmacological and clinical assessment of their role in treating ADHD and binge-eating disorder.

In this review, we critically evaluate the contribution of prodrugs to treating two related psychiatric disorders, attention-deficit hyperactivity disorder (ADHD) and binge-eating disorder (BED). ADHD is characterized by inattentiveness, distractibility, impulsiveness, and hyperactivity. BED is also an impulse-control disorder which leads to frequent, compulsive episodes of excessive eating (binges). Lisdexamfetamine (LDX; prodrug of d-amphetamine) is approved to treat both ADHD and BED. Serdexmethylphenidate (SDX; prodrug of d-threo-methylphenidate) is not clinically approved as monotherapy but, in a fixed-dose combination with immediate release d-threo-methylphenidate (Azstarys™), SDX is approved for managing ADHD in children/adolescents. The pharmacological actions of a stimulant mediate both its efficacy and side-effects. Therefore, daily management of ADHD or BED to maintain optimum efficacy and tolerability places highly restrictive requirements on the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of stimulant medications, especially prodrugs. Prodrugs must have good bioavailability and rapid metabolism to provide therapeutic efficacy soon after morning dosing combined with providing stimulant coverage throughout the day/evening. A wide selection of dosages and linear PK for the prodrug and its active metabolite are essential requirements for treatment of these conditions. The proposed neurobiological causes of ADHD and BED are described. The chemical, pharmacological and PK/PD properties responsible for the therapeutic actions of the prodrugs, LDX and SDX, are compared and contrasted. Finally, we critically assess their contribution as ADHD and BED medications, including advantages over their respective active metabolites, d-amphetamine and d-threo-methylphenidate, and also their potential for misuse and abuse.

Efficacy of methylphenidate treatment in childhood myotonic dystrophy type 1 and comorbid attention deficit hyperactivity disorder: A case report using eye tracking assessment.

INTRODUCTION: Despite the increased prevalence of comorbid attention deficit hyperactivity disorder (ADHD) in children with myotonic dystrophy type 1, the effects of methylphenidate treatment on associated cognitive deficits in this population is not yet investigated. CASE: We describe a case study of an eleven-year-old male patient with myotonic dystrophy type 1 and comorbid ADHD that was treated with methylphenidate in a twice daily regime (0.60 mg/kg/day). Positive effects on learning and cognition were reported by the parents and teachers. No negative side effects were reported. Sequential neuropsychological assessments before and 45 minutes after methylphenidate intake were conducted to quantify the cognitive effects of methylphenidate treatment. Significant improvements in regulation of attention were behaviorally observed and were quantified using eye tracking technology. CONCLUSION: We conclude that methylphenidate may be an effective treatment for ADHD-related cognitive deficits and learning difficulties in children with myotonic dystrophy type 1 which merits further research.

Adherence to Clinical Guidelines for Dose Finding and Monitoring Methylphenidate Use: A Medical Record Audit in Child and Adolescent Mental Health Care and Pediatric Settings.

Background: Guideline adherence is important to ensure optimal and safe use of methylphenidate for children and adolescents with attention-deficit/hyperactivity disorder (ADHD). We investigated adherence to Dutch guidelines regarding dosing and monitoring of methylphenidate in child and adolescent mental health care and pediatric treatment settings. Methods: Five hundred six medical records of children and adolescents were investigated in 2015 and 2016. We assessed adherence to the following guideline recommendations: (1) at least four visits during the dose-finding phase; (2) monitoring thereafter at least every 6 months; (3) measuring height and weight at least annually; and (4) the use of validated questionnaires to assess treatment response. Pearson's chi-squared test statistics were used to examine differences between settings. Results: Only a small portion of patients had at least four visits during the dose-finding phase (5.1% in the first 4 weeks to 12.4% in the first 6 weeks). Also, less than half of the patients (48.4%) were seen at least every 6 months. Height was recorded at least annually in 42.0% of patients, weight in 44.9%, and both recorded in a growth chart in 19.5%. Questionnaires to assess treatment response were only used in 2.3% of all visits. When comparing both settings, more patients in the pediatric settings were seen every 6 months, although height and weight were recorded more often in the mental health care setting. Conclusion: Overall, guideline adherence was low. Training of clinicians and adding guideline recommendations to electronic medical records templates may improve adherence. Additionally, we should aim to close the gap between guidelines and clinical practice by looking critically at the feasibility of guidelines.

Cost consequence analysis of Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

BACKGROUND: This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive. METHODS: A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors. RESULTS: Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001). DISCUSSION: Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer's disease while considering the burden on the healthcare system.

Open assessment of the therapeutic and rate-dependent effects of brain balance center® and interactive metronome® exercises on children with attention deficit hyperactivity disorder.

The aim of this open study was to delineate domains of benefit and effect size measures to design an appropriately powered randomized control trial to assess the efficacy of Brain Balance@ exercises and Interactive Metronome@ training (BB/IM) on ADHD symptoms in children. Participants underwent an extensive 15-week, 5 time per week, at-home training program. Results were assessed in 16 youths with ADHD (14M/2F, 10.8±1.7 years) who completed the program and compared to 8 typically developing controls (4M/F4, 11.0±1.8 years). BB/IM was associated with a significant reduction of 8.3 and 8.2 points on the Conner's Parent Rating Scale - Revised and the ADHD Rating Scale - IV. BB/IM was not associated with improvement on the Quotient ADHD System but with rate-dependent effects on hyperactivity and attention that were similar to previously reported effects of low dose methylphenidate. Both therapeutic and rate-dependent effects were observed on the Tower of London. The study provides information that could be used to design a randomized control trial, which is required for proof of efficacy. A key limitation is that 59% of the 39 enrolled participants with ADHD dropped out of the study and a new study should include multiple ratings during the course of treatment.

Efficacy and safety of methylphenidate and behavioural parent training for children aged 3-5 years with attention-deficit hyperactivity disorder: a randomised, double-blind, placebo-controlled, and sham behavioural parent training-controlled trial.

BACKGROUND: There is insufficient evidence to support treatment recommendations for preschool children aged 3-5 years with attention-deficit hyperactivity disorder (ADHD). We aimed to investigate the efficacy and safety of methylphenidate and behavioural parent training in reducing the frequency and severity of symptoms and improving global functioning in preschool children with ADHD. METHODS: We did an 8-week, randomised, double-blind, placebo-controlled and sham behavioural parent training-controlled clinical trial (the MAPPA Study) in children aged 3-5 years with moderate-to-severe ADHD. The trial was conducted at the Institute of Psychiatry, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, Brazil. Participants were randomly assigned (1:1:1) to receive immediate-release methylphenidate plus educational intervention (sham behavioural parent training), placebo medication plus behavioural parent training, or placebo medication plus educational intervention. Randomisation was done by an independent research manager by use of a permuted block randomisation procedure. Parents, teachers, study staff, and evaluators remained masked to group allocation. Methylphenidate and placebo were titrated to a maximum dose of 1·25 mg/kg per day administered orally twice daily, and behavioural parent training and the educational intervention were delivered weekly through 90 min sessions with both the child and parent, conducted by two psychologists or learning therapists. The primary outcomes were parents' and teachers' composite scores of the Swanson, Nolan, and Pelham-IV scale (SNAP-IV-P/T), the Clinical Global Impressions Severity (CGI-S) scale, and the Children's Global Assessment Scale (CGAS). This trial is registered with ClinicalTrials.gov, NCT02807870, and is now complete. All participants were invited to participate in an open observational follow-up, which is ongoing. FINDINGS: Between Aug 21, 2016, and Oct 21, 2019, 153 children were randomly assigned to receive methylphenidate plus the educational intervention (n=51), placebo plus behavioural parent training (n=51), or placebo plus the educational intervention (n=51). Nine (6%) children discontinued treatment. All participants were included in the intention-to-treat analysis. Children in the methylphenidate plus educational intervention group showed greater reductions in the SNAP-IV-P/T (endpoint mean difference -3·93 [95% CI -7·14 to -0·73], p=0·049; effect size -0·55 [95% CI -0·99 to -0·10]) and CGI-S scores (endpoint mean difference -0·49 [-0·82 to -0·17], p=0·0088; effect size -0·70 [-1·16 to -0·24]) and a greater increase in CGAS scores (endpoint mean difference 5·25 [95% CI 2·09 to 8·40], p=0·0036; effect size 0·80 [95% CI 0·32 to 1·28]) than children in the placebo plus educational intervention group. Children in the placebo plus behavioural parent training group did not have significantly different SNAP-IV-P/T scores (endpoint mean difference -3·18 [95% CI -6·38 to 0·02], p=0·077; effect size -0·44 [95% CI -0·89 to 0·003]) or CGI-S scores (endpoint mean difference -0·35 [-0·68 to -0·03], p=0·052; effect size -0·50 [-0·96 to -0·04]) compared to children in the placebo plus educational intervention group, but they had a greater increase in CGAS scores compared to the placebo plus educational intervention group (endpoint mean difference 3·69 [0·53 to 6·85], p=0·033; effect size 0·56 [0·08 to 1·04]). Children in the methylphenidate plus educational intervention versus placebo plus behavioural parent training group did not have statistically or clinically significant differences in primary outcomes. Children in the methylphenidate plus educational intervention group had more mild adverse events than the other two groups, and there were no between-group differences for moderate or severe adverse events. INTERPRETATION: Methylphenidate was effective in reducing ADHD symptoms and improving functionality, and behavioural parent training was effective in improving functionality for preschool children with ADHD after 8 weeks of treatment. FUNDING: São Paulo Research Foundation and Brazilian National Council for Scientific and Technological Development.

Understanding the Impact of Stimulants on Sleep in ADHD: Evidence from Systematic Assessment of Sleep in Adults.

Stimulants are widely prescribed to manage attention-deficit/hyperactivity disorder (ADHD) in adults. Stimulants promote wakefulness and can produce insomnia side effects. We hypothesized that systematic studies of sleep effects would reveal patterns of sleep impairment that may be important for clinicians to monitor and manage. We conducted a review and analysis of studies that measured sleep systematically during stimulant treatment in adults. We identified nine studies that met our search criteria, including four double-blind placebo-controlled studies. All studies recorded self-report subjective sleep quality data, three studies collected actigraphy data, and three studies collected polysomnography data. One study found better subjective sleep quality under open-label treatment conditions. Both polysomnography studies found improvement in aspects of sleep patterns. Two of the actigraphy studies suggested that adults receiving stimulant treatment may have less movement during sleep, and one showed reduction in amount of sleep. Further research could inform best practices for maintaining sleep quality during stimulant treatment.

Clinical characteristics of children and adolescents with ADHD with or without methylphenidate prescription at their first diagnostic assessment.

Attention Deficit/Hyperactivity Disorder (ADHD) is the most prevalent neurodevelopmental disorder diagnosed in the scholar age. It is associated with significant impairment in global functioning, and in moderate/severe presentations the outcome is critically dependent on pharmacological optimization of the multi-modal treatment. Methylphenidate (MPH) is the first-choice pharmacological treatment in children and adolescents with ADHD, with substantial evidence of significant efficacy and effectiveness on global functioning and symptoms' severity. There is some evidence supporting a few clinical and socio-demographic variables as predictors of pharmacological treatment prescription in children with ADHD independently of ADHD symptoms severity. However, it is warranted to investigate clinical and general psychopathological characteristics potentially associated with negative outcomes and the need for pharmacological treatment to inform appropriate prescription strategies. In this context, we compared 268 children and adolescents who were prescribed MPH (ADHD/MPH) for the first time after their first diagnostic assessment at our center, and 444 children and adolescents with ADHD (ADHD/noMPH) who were recommended non-pharmacological evidence-based interventions alone. ADHD/MPH group had higher severity of non-ADHD psychopathological symptoms compared to the ADHD/noMPH group, as documented by higher scores on the Child Behavior Checklist (CBCL) subscales, higher severity of ADHD symptoms, lower average IQ and lower adaptive levels independently of IQ. More specifically, beside externalizing symptoms, also internalizing symptoms were significantly higher in the ADHD/MPH group. The presence of significant non-ADHD psychopathology should be considered as a clinical factor associated with the need for MPH prescription in children and adolescents with ADHD.

Assessment of the lamina cribrosa in attention-deficit hyperactivity disorder.

PURPOSE: The aim of this study was to determine the usefulness of the lamina cribrosa thickness (LCT) and lamina cribrosa depth (LCD) in adolescence with attention-deficit hyperactivity disorder (ADHD) and compare with those receiving methylphenidate (MPH) and healthy controls. METHODS: Fifty-five children with ADHD (9.23 ± 1.92 years, mean ± standard deviation), 41 children with ADHD given MPH (9.24 ± 1.84 years), and 86 healthy controls (9.95 ± 2.16 years) were recruited for the study. All subjects were subjected to a complete eye exam and optical coherence tomography (OCT) was used to assess LCT and LCD. The severity of ADHD symptoms was evaluated by using parent-report measures, including Conners's Parent Rating Scale-Revised: Short Form (CPRS-R: S) and the Strengths and Difficulties Questionnaire: Parent Form (SDQ: P). RESULTS: The study showed a significant finding between the research groups with regard to LCT. LCT was shown to be significantly increased in ADHD subjects given MPH compared with the controls. However, LCD was not significantly different between cohorts. Also, a significant inverse correlation was found between the SDQ: P-Emotional Problems Subscale and LCT (r = -0.253; P = 0.030) in ADHD patients. CONCLUSION: Changes in lamina cribrosa (LC) in ADHD children receiving MPH suggest that the mechanism of action for MPH may target developing LC structures. More studies to define the relationship between MPH medications and the LC variations are defensible.

Metilfenidato e lisdexanfetamina para indivíduos com Transtorno do Déficit de Atenção com Hiperatividade / Methylphenidate and Lisdexamphetamine for Individuals with Attention Deficit Hyperactivity Disorder

INTRODUÇÃO: O TDAH é considerado uma condição do neurodesenvolvimento que se caracteriza por uma tríade de sintomas envolvendo desatenção, hiperatividade e impulsividade em um nível exacerbado e disfuncional para a idade. Os sintomas iniciam-se na infância, sendo capaz de persistir ao longo de toda a vida. Estas alterações ocorrem em diferentes contextos, podendo resultar em prejuízos afetivos, acadêmicos, ocupacionais, nas interações sociais e na qualidade de vida. O diagnóstico é feito com base em avaliação clínica e psicossocial completa. Geralmente, não são necessários exames de imagem ou laboratoriais para diagnóstico. Atualmente, o tratamento disponível no SUS é baseado em psicoterapias nas modalidades individual e em grupo. Entretanto, o tratamento medicamentoso pode ser necessário para o controle de sintomas e redução do impacto da doença nos diferentes domínios da vida do indivíduo. O objetivo do presente relatório é analisar as evidências científicas sobre o uso do metilfenidato (MPH) e da lisdexanfetamina (LDX) em paci

ADHD Diagnosis and Drug Use Estimates in France: A Case for Using Health Care Insurance Data.

Objective: Prevalence estimates for ADHD have been debated for decades. In France, the only available study states the prevalence rate in France ranges from 3.5% to 5.6% of children aged 6 to 12. It also evaluates that 3.48% of children aged 6 to 12 are treated with psychostimulants. The article uses a different method to determine whether these estimates hold true. Method: Estimating ADHD diagnosis and methylphenidate prescription rates can be done by analyzing national health care insurance system's data. We used data from the French Healthcare Insurance as reported by the National Agency for Medicines and Health Products Safety. Results: We claim that an adequate estimate of the ADHD prevalence rate in France fluctuates around 0.3% of children aged 6 to 11. Discussion: Methodological biases in ADHD prevalence studies and factors contributing to the low level of prescription in France need to be assessed. Conclusion: We call for supplementary investigations in health care insurance databases to conduct contradictory studies.

Assessment of changes in the macula and optic nerve head using optical coherence tomography in patients with attention deficit hyperactivity disorder. / Evaluación de los cambios en la mácula y en el nervio óptico mediante tomografía de coherencia óptica en pacientes con trastorno por déficit de atención e hiperactividad.

INTRODUCTION: To assess if there are any differences in macular and papillary thickness using optical coherence tomography (OCT) in patients with attention deficit hyperactivity disorder (ADHD) compared with a control group, including if there are differences between ADHD patients with and without treatment. METHODS: Prospective observational study including 92 eyes of 46 patients divided into 2 groups: 46 eyes of 23 patients with ADHD, and a control group of 46 eyes of 23 healthy patients. The group of patients with ADHD was subdivided into those on treatment with methylphenidate (n=28) and those not on treatment (n=18). The macular thickness, the ganglion cell complex (GCC), and the retinal nerve fibre layer (RNFL) at the papillary level were measured in 12 sectors. RESULTS: A lower central macular thickness was observed in the ADHD patients than in the controls (257.4±20µm versus 267.5±20µm, P=.013), with no differences observed in the GCC (P=.566), or in the RNFL (P=.095). There were no differences in the patients with ADHD with and without treatment, as regards macular thickness and the GCC (P=.160 and P=.375 respectively), but a lower foveal thickness (P=.018) and RNFL in 5/12 sectors at the papillary level (P=.033) were observed in those without treatment. CONCLUSIONS: A lower macular thickness was observed in patients with ADHD than in controls. In addition, patients with ADHD without treatment had a lower thickness of the fovea and RNFL than those patients on treatment.

Differentiating depression and ADHD without depression in adults with processing-speed measures.

OBJECTIVE: We evaluated processing-speed and shift-cost measures in adults with depression or attention-deficit hyperactivity disorder (ADHD) and monitored the effects of treatment. We hypothesised that cognitive-speed and shift-cost measures might differentiate diagnostic groups. METHODS: Colour, form, and colour-form stimuli were used to measure naming times. The shift costs were calculated as colour-form-naming time minus the sum of colour- and form-naming times. Measurements were done at baseline and end point for 42 adults with depression and 42 with ADHD without depression. Patients with depression were treated with transcranial pulsed electromagnetic fields and patients with ADHD with methylphenidate immediate release. RESULTS: During depression treatment, reductions in naming times were recorded weekly. One-way analysis of variance indicated statistical between-group differences, with effect sizes in the medium range for form and colour-form. In both groups, naming times were longer before than after treatment. For the ADHD group, shift costs exceeded the average-normal range at baseline but were in the average-normal range after stabilisation with stimulant medication. For the depression group, shift costs were in the average-normal range at baseline and after treatment. Baseline colour-form-naming times predicted reductions in naming times for both groups, with the largest effect size and index of forecasting efficiency for the ADHD group. CONCLUSIONS: The cognitive-processing-speed (colour-form) and shift-cost measures before treatment proved most sensitive in differentiating patients with depression and ADHD. Reductions in naming times for the depression group were suggested to reflect improved psychomotor skills rather than improved cognitive control.

Interventions for tic disorders: An updated overview of systematic reviews and meta analyses.

To conduct an updated overview of systematic reviews (SRs) summarizing the efficacy and safety of various strategies used to treat tic disorders (TDs) in children. We searched the Cochrane Library, PubMed, EMBASE, and relevant reference lists for articles published between the search deadline from our last overview and April 2019 and included 16 SRs. The results presented that antipsychotics, a2-adrenergic receptor agonists, and HRT/CBIT still appeared to be the most robust evidence-based options for the treatment of TDs. Compared with our last overview, more robust evidence showed that aripiprazole and acupuncture was effective treatment in treating children TDs, and DBS for medication-refractory and severely affected patients. In addition, physical activity or exercise may be promising treatments, and the clonidine adhesive patch is an effective, safe, and convenient treatment option for TDs. Moreover, methylphenidate, guanfacine, and desipramine appeared to reduce ADHD symptoms in children with tics. However, no research studies have examined HRT/CBIT alone compared with HRT/CBIT in combination with medication. More high-quality clinical trials comparing different interventions for TDs including economic evaluations should be encouraged.

Drug Prescriptions for Children With ADHD in Japan: A Study Based on Health Insurance Claims Data Between 2005 and 2015.

Objective: The aim of this study is to investigate the trend of prescription drugs for children with ADHD in Japan. Method: Using health insurance claims data of 3,672,951 people between January 2005 and December 2015, we investigated the trend of prescription drugs for 7,856 children with ADHD. Results: After approval in 2007, the proportion of prescriptions for methylphenidate-osmotic-controlled release oral delivery system tablets was 31.4% in 2009 (adjusted odds ratio [AOR] = 2.72; 95% confidence interval [CI] = [2.12, 3.51]) and reached a plateau approximately after 2009 (AOR = 0.96; 95% CI = [0.94, 0.98]). The proportion of prescriptions for atomoxetine increased from 6.1% in 2008 to 21.8% in 2014 (AOR = 1.12; 95% CI = [1.13, 1.18]). The proportion of prescriptions for aripiprazole and ramelteon increased (all trend p < .001). Conclusion: Prescriptions of drugs for children with ADHD have changed. We need to monitor the safety of ADHD medications among children with ADHD.

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.

The countervailing forces behind France's low Ritalin consumption.

In recent decades pharmaceutical consumption has skyrocketed, growing from $43 US billion in 1985 to over $1143 billion in 2017. In trying to understand the source of this growth, social scientists have identified the key actors driving medication use and the processes through which they are driving it. However, much less attention has been devoted to understanding the forces that constrain medication consumption. This information is crucial for developing a deeper understanding of medication consumption, one that explains how context mediates the ability of key actors to shape medication consumption. To address this gap, I examine France's low consumption of psychostimulants to treat ADHD symptoms. France is a strategic case to analyze because it diverges dramatically from comparative cases: while 7% of U.S. children are medicated with psychostimulants, the same is true for only 0.2% of French children. To explain the French case I use the theory of countervailing powers. Informed by interviews with key informants, the French medical literature on psychostimulants and secondary sources, I explain how the state, medical experts and consumers have acted as countervailing forces against pharmaceutical interests. In doing so, I provide deeper insight about how context can limit the pharmaceutical industry's power.

Consumption of methylphenidate and atomoxetine in the private healthcare sector in South Africa: a longitudinal study.

Background Globally Attention-Deficit/Hyperactivity Disorder (ADHD) has been in the spotlight. Despite some controversies, treatment of ADHD remains the cornerstone of patient care. Objective To describe the consumption of methylphenidate and atomoxetine in the private healthcare sector in South Africa over a four-year period (2013-2016). Method Data were extracted from the Intercontinental Marketing Service (IMS) database for the drug utilisation study. Consumption patterns were expressed as number of Defined Daily Doses (DDDs)/1000 inhabitants/day and number of DDDs/1000 inhabitants/month. Results Methylphenidate (95.85%) was the medication of choice when compared to atomoxetine (4.15%) in 2013. The corresponding figures for 2016 were 96.40% and 3.60%. Consumption of ADHD medication showed slight changes over the 4-year period. If only the private healthcare sector population is considered, consumption of methylphenidate was 6.010 DDDs/1000 inhabitants/day in 2013, and 7.827 DDDs/1000 inhabitants/day in 2016. A previous study (1994-1996) reported 0.12 DDDs/1000 inhabitants/day for methylphenidate. Consumption of atomoxetine was 0.044 DDDs/1000 inhabitants/day in 2013 and 0.050 DDDs/1000 inhabitants/day in 2016. Conclusion Consumption showed an increase in use of methylphenidate in South Africa, with small changes observed over the study period. Further studies are required.