Amfetamine 5mg / Dexamfetamine 5mg modified-release capsules

BackgroundMany children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically relevant increases for some individual patients, and/or increase the risk for serious cardiovascular adverse events such as stroke or sudden death.ObjectivesTo evaluate potential cardiovascular effects of these treatments, we conducted a systematic review and meta-analysis of the effects of methylphenidate (MPH), amphetamines (AMP), and atomoxetine (ATX) on diastolic and systolic blood pressure (DBP, SBP) and heart rate (HR) in children and adolescents with ADHD.MethodsWe conducted systematic searches in electronic databases (PsychINFO, EMBASE and Medline) to identify published trials which involved individuals who were (i) diagnosed with ADHD and were aged between 0-18 years; (ii) treated with MPH, AMP or ATX and (iii) had their DBP and SBP and/or HR measured at baseline (pre) and the endpoint (post) of the study treatment. Studies with an open-label design or a double-blind randomised control design of any duration were included. Statistical analysis involved calculating differences between pre- and post-treatment measurements for the various cardiovascular parameters divided by the pooled standard deviation. Further, we assessed the percentage of clinically relevant increased BP or HR, or documented arrhythmias.ResultsEighteen clinical trials met the inclusion criteria (10 for MPH, 5 for AMP, and 7 for ATX) with data from 5837 participants (80.7% boys) and average duration of 28.7 weeks (range 4-96 weeks). All three medications were associated with a small, but statistically significant pre-post increase of SBP (MPH: standard mean difference [SMD] 0.25, 95% confidence interval [CI] 0.08-0.42, p ConclusionsStatistically significant pre-post increases of SBP, DBP and HR were associated with AMP and ATX treatment in children and adolescents with ADHD, while MPH treatment had a statistically significant effect only on SBP in these patients. These increases may be clinically significant for a significant minority of individuals that experience larger increases. Since increased BP and HR in general are considered risk factors for cardiovascular morbidity and mortality during adult life, paediatric patients using ADHD medication should be monitored closely and regularly for HR and BP.

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AimStimulant medications are an evidence-based treatment for ADHD. However, stimulant medications are associated with a risk of misuse and diversion. Given the paucity of research, this systematic review evaluates the prevalence of misuse and diversion of stimulant medication by those who are prescribed the medication for a diagnosis of ADHD, and explores risk factors for misuse and diversion.MethodsThis systematic review was registered with PROSPERO (CRD42023469041). A systematic search of original articles from PubMed and PsycInfo on the topic of interest over a period of 10 years (2012-2023) was conducted. Risk of bias was assessed through JBI Critical Appraisal Checklist for Prevalence Studies. A meta-analysis was conducted using JBI SUMARI software.ResultsTwelve cross sectional surveys met the inclusion criteria, with study populations ranging from 88 respondents to 10,000 respondents. Meta-analysis found an average prevalence of past year prescription stimulant medication misuse of 22.6%, past year diversion of 18.2%, and lifetime diversion of 17.9%. Risk factors for misuse included being prescribed an amphetamine-based stimulant, reporting comorbid depressive and anxiety symptoms, and believing that misuse was not associated with risks. Risk factors for diversion included exposure to peers who were misusing stimulant medication, and having surplus medication available.ConclusionWith more than one in five people reporting misuse of their prescribed stimulant medication, and one in six diverting their prescribed stimulant medication, comprehensive risk assessment and risk mitigation strategies are needed. Further research in a variety of geographic and demographic settings is needed to develop effective risk assessment tools and targeted interventions.

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IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles.Methods and analysisWe will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings.Ethics and disseminationNo ethical issues are foreseen. Results from this study will be published in a peer-reviewed journal and possibly presented at relevant national and international conferences.Trial registration numberCRD42014008976.

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Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among school-aged children. It is highly symptomatic and associated with significant impairment. This review examines the role of stimulant medications in the treatment of children and adolescents with ADHD. Published clinical studies that compared methylphenidate- and amfetamine-based stimulants in children and adolescents with ADHD support the therapeutic utility of stimulant treatments, and suggest robust efficacy and acceptable safety outcomes in groups treated with either stimulant. Evidence-based guidelines agree that each patient with ADHD is unique and individual treatment strategies that incorporate both drug and non-drug treatment options should be sought. In seeking to optimize individual response and outcomes to stimulant therapy, important considerations include the selection of stimulant class, the choice of long- or short-acting stimulant formulations, addressing effectively any emergent adverse effects and strategies aimed at enhancing adherence to dosing regimen and persistence on therapy.

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