Switch to Lisdexamfetamine in the Treatment of Attention-Deficit Disorder at a Psychiatric Outpatient Clinic for School-Aged Children: A Danish Cohort Study.

Objectives: This study aimed to examine switch from first-line methylphenidate (MPH) to lisdexamfetamine (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD). Methods: This is a retrospective observational study based on systematic review of patient records of all children (7-13 years) diagnosed with ADHD and referred to a Danish specialized outpatient clinic. The study included 394 children switching from MPH to LDX as either second-line or third-line treatment (atomoxetine [ATX] as second-line treatment) during the study period from April 1, 2013, to November 5, 2019. Results: One in five children switched from MPH to LDX at some point during the study period. The most frequent reasons for switching to LDX were adverse effects (AEs; 70.0% for MPH, 68.3% for ATX) and lack of efficiency (52.0% for MPH, 72.7% for ATX). Top five AEs of LDX were decreased appetite (62.4%), insomnia (28.7%), irritability/aggression (26.1%), weight decrease (21.1%), and mood swings (13.9%). MPH and LDX had similar AE profiles, yet most AEs were less frequent after switching to LDX. At the end of the study period, the majority were prescribed LDX as second-line rather than third-line treatment (86.1% in 2019). However, the likelihood of LDX as second-line treatment decreased with the number of psychiatric comorbidities, ADHD symptom severity as assessed by parents, and if AEs were a reason for MPH discontinuation. Among children observed for at least 1 year after initiation of LDX, 41.3% continued LDX treatment for a year or longer. LDX continuation was less likely if AEs were a reason for MPH discontinuation. Similarly to MPH and ATX, the most frequent reasons for LDX discontinuation were AEs (74.4%) and lack of efficiency (34.7%). Implications: The findings support LDX as an important option in the personalized treatment of children with ADHD and may support prescribers in the clinical decision-making on switching medication.

Measuring Objective and Subjective Sleep during Lisdexamfetamine Treatment of Acute Methamphetamine Withdrawal: A Feasibility Study.

INTRODUCTION: Sleep disturbance is common during methamphetamine (MA) use and withdrawal; however, the feasibility of combined subjective-objective measurement of sleep-wake has not been shown in this population. Actigraphy is a well-established, non-invasive measure of sleep-wake cycles with good concordance with polysomnography. This study aimed to investigate the feasibility and utility of using actigraphy and sleep diaries to investigate sleep during MA withdrawal. METHODS: We conducted a feasibility and utility study of actigraphy and sleep diaries during a clinical trial of lisdexamfetamine for MA withdrawal. Participants were inpatients for 7 days, wore an actigraph (Philips Actiwatch 2) and completed a modified Consensus Sleep Diary each morning. Participants were interviewed between days 3-5. RESULTS: Ten participants (mean age 37 years, 90% male) were enrolled. No participant removed the device prematurely. Participants interviewed (n = 8) reported that the actigraph was not difficult or distracting to wear or completion of daily sleep diary onerous. Actigraphic average daily sleep duration over 7 days was 568 min, sleep onset latency 22.4 min, wake after sleep onset (WASO) 75.2 min, and sleep efficiency 83.6%. Sleep diaries underreported daily sleep compared with actigraphy (sleep duration was 56 min (p = 0.008) and WASO 47 min (p < 0.001) less). Overall sleep quality was 4.4 on a nine-point Likert scale within the diary. CONCLUSIONS: Continuous actigraphy is feasible to measure sleep-wake in people withdrawing from MA, with low participant burden. We found important differences in self-reported and actigraphic sleep, which need to be explored in more detail.

LISDEXAMFETAMINE (VYVANSE) USE ASSOCIATED WITH BRANCH RETINAL ARTERY OCCLUSION.

BACKGROUND/PURPOSE: Branch retinal artery occlusions (BRAO) are primarily associated with the aging population and are rare in young adults. The etiology of BRAO includes embolic or nonembolic sources. Lisdexamfetamine has been associated with vasospastic ischemic events in multiple areas of the body. However, there are currently no reported cases of BRAO associated with lisdexamfetamine use. Here, we present a case that suggests a correlation between lisdexamfetamine use and a nonembolic BRAO in a young adult man. METHODS/RESULTS: A 32-year-old man presented with sudden left eye blurred vision 17 days after beginning lisdexamfetamine. Fundus examination confirmed the BRAO diagnosis. Following evaluation by a retina specialist, vasospasm was considered the most likely cause for the BRAO. Other possible etiologies were unlikely due to diagnostic testing. CONCLUSION: The temporal association between lisdexamfetamine and BRAO symptom onset suggests vasospastic occlusion. Lisdexamfetamine-associated adverse events should be considered as a possible etiology for BRAO.

Lisdexamfetamine for the treatment of acute methamphetamine withdrawal: A pilot feasibility and safety trial.

BACKGROUND: There is no effective treatment for methamphetamine withdrawal. This study aimed to determine the feasibility and safety of a tapering dose of lisdexamfetamine for the treatment of acute methamphetamine (MA) withdrawal. METHODS: Open-label, single-arm pilot study, in an inpatient drug and alcohol withdrawal unit assessing a tapering dose of oral lisdexamfetamine dimesylate commencing at 250 mg once daily, reducing by 50 mg per day to 50 mg on Day 5. Measures were assessed daily (days 0-7) with 21-day telephone follow-up. Feasibility was measured by the time taken to enrol the sample. Safety was the number of adverse events (AEs) by system organ class. Retention was the proportion to complete treatment. Other measures included the Treatment Satisfaction Questionnaire for Medication (TSQM), the Amphetamine Withdrawal Questionnaire and craving (Visual Analogue Scale). RESULTS: Ten adults seeking inpatient treatment for MA withdrawal (9 male, median age 37.1 years [IQR 31.7-41.9]), diagnosed with MA use disorder were recruited. The trial was open for 126 days; enroling one participant every 12.6 days. Eight of ten participants completed treatment (Day 5). Two participants left treatment early. There were no treatment-related serious adverse events (SAEs). Forty-seven AEs were recorded, 17 (36%) of which were potentially causally related, all graded as mild severity. Acceptability of the study drug by TSQM was rated at 100% at treatment completion. Withdrawal severity and craving reduced through the admission. CONCLUSION: A tapering dose regimen of lisdexamfetamine was safe and feasible for the treatment of acute methamphetamine withdrawal in an inpatient setting.

Trial protocol of an open label pilot study of lisdexamfetamine for the treatment of acute methamphetamine withdrawal.

INTRODUCTION: Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients. METHODS: A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary). DISCUSSION: This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention.

What is the potential for abuse of lisdexamfetamine in adults? A preclinical and clinical literature review and expert opinion.

INTRODUCTION: Lisdexamfetamine dimesylate (LDX) is a prodrug approved for attention deficit/hyperactivity disorder and for moderate-to-severe binge eating disorder in adults in some countries. AREA COVERED: We aimed to specify the abuse potential of LDX in adults, using a review of pharmacokinetic/pharmacodynamic (PK/PD), animal, clinical, and pharmaco-epidemiological studies, through a PubMed search since inception until May 2021 using the following keywords: "lisdexamfetamine AND ('misuse' OR 'abuse' OR 'diversion' OR 'addiction')". EXPERT OPINION: Most of the studies highlighted a longer Tmax than dexamphetamine leading to a delayed onset of effects and a decreased Cmax. These PK parameters were often associated with a diminished feeling of euphoria, in comparison to immediate-release dexamphetamine. The potential for abuse was also limited by the prodrug property of LDX, thus reducing the risk of misuse. Nevertheless, all the data were not convergent, as some authors reported similar Cmax for LDX and dexamphetamine and reinforcing properties with a dose-dependent effect. Epidemiological studies found that abuse rates of LDX were substantially lower than those of immediate-release dexamphetamine. Overall, although LDX abuse seems possible, we did not find evidence concerning current safety signal. However, more long-term pharmaco-epidemiological studies are still needed to confirm this finding.

Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA) in a Patient Taking Lisdexamfetamine.

Stimulant medications like amphetamines have been associated with various cardiovascular complications like coronary artery spasm, coronary dissections and thrombus formation, the pathophysiology of which is theorized to be the endothelial damage induced by the medication and the inflammatory cascade that follows. We report a case of 52-year-old male on lisdexamfetamine, a newer stimulant agent used for attention deficit hyperactivity disorder (ADHD) who presented with sudden chest pain and ECG changes concerning for myocardial infarction and mildly elevated troponins. However, coronary angiogram showed no obstructive coronary artery disease and there was spontaneous resolution of his symptoms and ECG changes.

Efficacy and Safety of Lisdexamfetamine in Preschool Children With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To evaluate the acute efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) vs placebo (PBO) in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD). METHOD: This phase 3, double-blind, fixed-dose study randomly assigned children (aged 4-5 years) with ADHD to 6 weeks of LDX (5, 10, 20, 30 mg) or PBO. The prespecified primary (change from baseline at week 6 in ADHD Rating Scale IV, Preschool version, total score [ADHD-RS-IV-PS-TS]) and key secondary (Clinical Global Impression-Improvement [CGI-I] score at week 6) efficacy endpoints were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and changes in pulse and blood pressure (BP). RESULTS: The study comprised 199 participants randomly asigned 5:5:5:5:6 to receive 5, 10, 20, 30 mg LDX or PBO, respectively. Least squares (LS) mean (95% CI) treatment difference at week 6 between pooled LDX (10, 20, 30 mg) and PBO was statistically significant for ADHD-RS-IV-PS-TS change (-5.9 [-11.01, -0.78], p = .0242; effect size [ES], -0.43). CGI-I scores improved (ie, 1-2 on CGI-I) in 41.7% for pooled LDX and 24.3% for PBO (p = .0857). The LS mean (95% CI) treatment difference between pooled LDX and PBO for CGI-I score at week 6 was -0.6 (-1.03, -0.16; p = .0074; ES, -0.52). Frequency of TEAEs was 46.6% across all 4 LDX doses vs 42.2% with PBO; the most frequent TEAEs were decreased appetite (13.7% vs 8.9%, respectively) and irritability (9.6% vs 0%). Discontinuations because of TEAEs were 5.5% for all LDX doses and 4.4% for PBO. Mean ± SD pulse/BP changes from baseline at week 6/early termination were numerically greater with LDX vs PBO (pulse beats/min: 2.7 ± 10.79 vs 1.2 ± 9.90; systolic BP, mm Hg: 1.0 ± 7.51 vs 0.3 ± 6.06; diastolic BP, mm Hg: 1.7 ± 5.90 vs 0.0 ± 6.88). CONCLUSION: In children aged 4 to 5 years with ADHD, LDX was more efficacious than PBO in reducing symptoms. The observed ES for change in ADHD-RS-IV-PS-TS appears to be smaller in magnitude than has been reported for studies of LDX conducted in older children and adolescents. LDX was generally well tolerated, and no new safety signals were identified. CLINICAL TRIAL REGISTRATION INFORMATION: Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-Deficit/Hyperactivity Disorder; http://www. CLINICALTRIALS: gov; NCT03260205.

A Long-Term, Open-Label Safety and Tolerability Study of Lisdexamfetamine Dimesylate in Children Aged 4-5 Years with Attention-Deficit/Hyperactivity Disorder.

Objective: To evaluate the long-term safety and tolerability of lisdexamfetamine dimesylate (LDX) in preschool-aged children (4-5 years of age inclusive) diagnosed with attention-deficit/hyperactivity disorder (ADHD). Methods: This phase 3 open-label study (ClinicalTrials.gov registry: NCT02466386) enrolled children aged 4-5 years meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria for a primary ADHD diagnosis and having baseline ADHD Rating Scale-IV Preschool version total scores (ADHD-RS-IV-PS-TS) ≥24 for girls or ≥28 for boys and baseline Clinical Global Impressions-Severity scores ≥4. Participants were directly enrolled or enrolled after completing one of two antecedent short-term LDX studies. Over 52 weeks of treatment, participants received once-daily dose-optimized LDX (5-30 mg). Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and vital sign changes. Clinical outcomes included ADHD-RS-IV-PS-TS changes from baseline. Results: Among 113 participants in the safety set, optimized LDX dose was 5, 10, 15, 20, and 30 mg in 1 (0.9%), 12 (10.6%), 21 (18.6%), 26 (23.0%), and 53 (46.9%) participants, respectively. Of the safety set, 69 participants (61.1%) completed the study. TEAEs were reported in 76.1% of participants; no serious TEAEs were reported. Only one type of TEAE was reported in >10% of participants (decreased appetite, 15.9%). Mean ± standard deviation (SD) changes in vital signs and body weight from baseline to week 52/or early termination (ET; n = 101) were 1.9 ± 7.73 mmHg for systolic blood pressure, 3.1 ± 7.58 mmHg for diastolic blood pressure, 4.7 ± 11.00 bpm for pulse, and 0.6 ± 1.38 kg for body weight. Over the course of the study, mean ± SD change in ADHD-RS-IV-PS-TS from baseline to week 52/ET was -24.2 ± 13.34 (n = 87). Conclusions: In this long-term 52-week study of children aged 4-5 years with ADHD, dose-optimized LDX (5-30 mg) was well tolerated and associated with reductions from baseline in ADHD symptoms.

Bilateral Acute Angle Closure in a Pediatric Patient Taking Lisdexamfetamine Dimesylate (Vyvanse).

Attention-deficit/hyperactivity disorder is commonly treated with amphetamines as first line therapy. Rare case reports have shown amphetamines are associated with open angle glaucoma. We report a rare case of a 14-year-old male who presented with bilateral acute angle closure presumed to be related to his use of lisdexamfetamine dimesylate (Vyvanse). The patient's medication was discontinued which resulted in complete resolution of angle closure.

Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults.

BACKGROUND: Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone. METHODS: In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (d-amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations. RESULTS: Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33-100.82), area under the concentration-time curve from 0 to the last measurable time (AUC0-t) = 99.19% (96.53-101.91), and area under the concentration-time curve from 0 to infinity (AUCinf) = 99.23% (96.61-101.93). Lisdexamfetamine: Cmax = 112.78% (109.93-115.71), AUC0-t = 109.64% (105.25-114.22), and AUCinf = 109.52% (105.19-114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity. CONCLUSIONS: Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or d-amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated.

Pharmacologic treatment of attention deficit hyperactivity disorder in adults: A systematic review and network meta-analysis.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) affects approximately 3% of adults globally. Many pharmacologic treatments options exist, yet the comparative benefits and harms of individual treatments are largely unknown. We performed a systematic review and network meta-analysis to assess the relative effects of individual pharmacologic treatments for adults with ADHD. METHODS: We searched English-language published and grey literature sources for randomized clinical trials (RCTs) involving pharmacologic treatment of ADHD in adults (December 2018). The primary outcome was clinical response; secondary outcomes were quality of life, executive function, driving behaviour, withdrawals due to adverse events, treatment discontinuation, serious adverse events, hospitalization, cardiovascular adverse events, and emergency department visits. Data were pooled via pair-wise meta-analyses and Bayesian network meta-analyses. Risk of bias was assessed by use of Cochrane's Risk of Bias tool, and the certainty of the evidence was assessed by use of the GRADE framework. RESULTS: Eighty-one unique trials that reported at least one outcome of interest were included, most of which were at high or unclear risk of at least one important source of bias. Notably, only 5 RCTs were deemed at overall low risk of bias. Included pharmacotherapies were methylphenidate, atomoxetine, dexamfetamine, lisdexamfetamine, guanfacine, bupropion, mixed amphetamine salts, and modafinil. As a class, ADHD pharmacotherapy improved patient- and clinician-reported clinical response compared with placebo (range: 4 to 15 RCTs per outcome); however, these findings were not conserved when the analyses were restricted to studies at low risk of bias, and the certainty of the finding is very low. There were few differences among individual medications, although atomoxetine was associated with improved patient-reported clinical response and quality of life compared with placebo. There was no significant difference in the risk of serious adverse events or treatment discontinuation between ADHD pharmacotherapies and placebo; however, the proportion of participants who withdrew due to adverse events was significantly higher among participants who received any ADHD pharmacotherapy. Few RCTs reported on the occurrence of adverse events over a long treatment duration. CONCLUSIONS: Overall, despite a class effect of improving clinical response relative to placebo, there were few differences among the individual ADHD pharmacotherapies, and most studies were at risk of at least one important source of bias. Furthermore, the certainty of the evidence was very low to low for all outcomes, and there was limited reporting of long-term adverse events. As such, the choice between ADHD pharmacotherapies may depend on individual patient considerations, and future studies should assess the long-term effects of individual pharmacotherapies on patient-important outcomes, including quality of life, in robust blinded RCTs. REGISTRATION: PROSPERO no. CRD 42015026049.

Review of lisdexamfetamine dimesylate in children and adolescents with attention deficit/hyperactivity disorder.

OBJECTIVE: Lisdexamfetamine dimesylate is a stimulant prodrug with low abuse and diversion potential that is used in treatment of attention deficit hyperactivity disorder (ADHD) in children, adolescents and adults. This current literature review article aims to examine safety and efficacy of LDX in children and adolescents for the treatment of ADHD based on currently available data. METHODS: Relevant English language articles were identified through computerized searches of the MEDLINE database (PubMed and EMBASE) and clinical trials registry up to January 2020 using the following search terms: lisdexamfetamine dimesylate, pro-drug stimulant, attention-deficit and hyperactivity disorders, ADHD, safety, efficacy, children, adolescents, Vyvanse. Forty-two articles were reviewed, 34 of which were included into this review, selected by the limit "clinical trials". This article represents the pharmacological profile, efficacy and safety data of LDX for the treatment of ADHD in children and adolescents. RESULTS: The collection of studies reviewed identified that LDX was both safe and efficacious in the treatment of ADHD. The most commonly exhibited side effects were appetite suppression, weight loss, headache and insomnia. In comparison to placebo, LDX significantly improved ADHD symptoms and overall quality of life in children and adolescents. In comparison to atomoxetine, LDX showed statistically significant improvements in inattention, impulsivity, and activities of daily living. In comparison to OROS-MPH and placebo, LDX and OROS-MPH showed improvements with the CGI-I score, and ADHD-RS-IV, however, LDX was superior. CONCLUSION: Patients have seen statistically significant improvements in their ADHD symptomatology in the classroom environment, health related quality of life, and their overall behavior in comparison to placebo, atomoxetine, and OROS-MPH. However, clinical judgment should be utilized when prescribing LDX due to patient specific needs and the side effect profile.

Dose Adjustment of Stimulants for Children with Attention-Deficit/Hyperactivity Disorder: A Retrospective Chart Review of the Impact of Exceeding Recommended Doses.

BACKGROUND: When children with attention-deficit/hyperactivity disorder (ADHD) are treated with stimulant medication, the dose is established clinically by dose adjustment over time. Little is known about children who are not adequately treated when they reach a designated maximum dose, or the consequences of exceeding this dose. OBJECTIVE: The aim of this study was to determine the characteristics of and side effects observed in children optimised to high dose (HD) versus regular dose (RD) stimulants. METHOD: Children treated by one paediatrician (AP) in Western Sydney, Australia with HD stimulants (n = 52) were identified using an electronic database; controls on RD stimulant (n = 118) were matched by prescription date with the cases' first HD prescription. HD was defined as methylphenidate > 2 mg/kg/day or > 108 mg/day; dexamphetamine > 1 mg/kg/day or > 50 mg/day; lisdexamfetamine > 70 mg/day. In all children, the dose was adjusted over time to optimise the clinical response. Clinical characteristics, anthropometric measures, reported side effects and reasons for dose changes were extracted from the clinical charts by LR, VS and CS. The HD and RD cohorts were compared using chi-square for categorical data and t tests for continuous data. RESULTS: The HD cohort included more boys (88% vs 75%, p = 0.041) and more oppositional defiant disorder (83% vs 55%, p = 0.001). They started stimulants younger (6.40 ± 1.67 vs 8.28 ± 2.77 years, p < 0.001) and had more growth attenuation (Δ height z-score - 0.41 ± 0.55 vs - 0.09 ± 0.58, p = 0.001; Δ weight z-score - 0.56 ± 0.82 vs - 0.18 ± 0.66, p = 0.002). The growth attenuation mainly occurred before the dose reached the HD range. Diminishing stimulant effectiveness was the commonest reason for a dose increase in either cohort, the most prominent recurring symptoms being persistent anger/aggression in the HD and poor concentration in the RD cohort. The commonest reason for dose reduction in the HD cohort was that a dose increase gave no added benefit; dose reduction or change of drug due to subdued/depressed behaviour was more frequent in RD children. Apart from growth attenuation, no serious complications were reported in the HD group. CONCLUSIONS: In this preliminary study, dose adjustment over time in some patients meant using higher doses than those generally recommended. These children experienced more growth attenuation but recorded no other significant treatment complications. Determining the dose purely on clinical grounds by careful dose adjustment over time appears reasonable, but more data on this issue is required to clarify the efficacy and tolerability of exceeding the recommended doses of stimulants when treating ADHD.

Lisdexamfetamine Dimesylate for Preschool Children with Attention-Deficit/Hyperactivity Disorder.

Objectives: Describe the safety and tolerability of lisdexamfetamine dimesylate (LDX) and provide data on clinical effects for efficacy-related endpoints and pharmacokinetics in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD). Methods: This phase 2, multicenter, open-label, dose-optimization study (ClinicalTrials.gov registry: NCT02402166) was conducted at seven U.S. sites between April 15, 2015, and June 30, 2016. Children (4-5 years of age) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for ADHD and having ADHD Rating Scale-IV Preschool version (ADHD-RS-IV-PS) total scores ≥28 (boys) or ≥24 (girls) were eligible. Open-label LDX (8-week duration) was initiated at 5 mg and titrated to 30 mg until achieving an optimal dose. Assessments included treatment-emergent adverse events (TEAEs), vital sign changes, ADHD-RS-IV-PS total score changes, and pharmacokinetic evaluations. Results: Among 24 participants, the most frequently reported TEAE was decreased appetite (8/24; 33%). At week 8/early termination, mean (standard deviation) systolic and diastolic blood pressure and pulse changes from baseline were -1.1 (7.31) and 1.5 (6.93) mmHg and -0.8 (12.75) bpm, respectively. The mean (95% confidence interval) change from baseline ADHD-RS-IV-PS total score at the final on-treatment assessment was -26.1 (-32.2 to -20.0). Pharmacokinetic parameters of d-amphetamine, a major active metabolite of LDX, were characterized: d-amphetamine exposure increased with LDX dose; mean tmax and t1/2, respectively, ranged from 4.00 to 4.23 hours and 7.18 to 8.46 hours. Conclusions: In preschool-aged children with ADHD, LDX was generally well tolerated and reduced ADHD symptoms, consistent with observations in children 6-17 years of age. Based on these findings, a starting LDX dose as low as 5 mg in phase 3 studies in preschool-aged children is supported.

Assessment of Amphetamine Withdrawal Symptoms of Lisdexamfetamine Dimesylate Treatment for Adults With Binge-Eating Disorder.

OBJECTIVE: To determine whether physical dependence developed during lisdexamfetamine dimesylate treatment, as evidenced by presence of withdrawal symptoms after treatment cessation in adults with binge-eating disorder (BED) treated for up to 38 weeks. METHODS: Three studies enrolled adults with DSM-IV-TR-defined BED. In two 12-week, randomized, double-blind, placebo-controlled studies conducted from November 2012 to September 2013, participants were treated with placebo or dose-optimized lisdexamfetamine (50 or 70 mg). In a double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study conducted from January 2014 to April 2015, participants categorized as responders after 12 weeks of open-label lisdexamfetamine (50 or 70 mg) were randomized to continued lisdexamfetamine or placebo for 26 weeks. The Amphetamine Cessation Symptom Assessment (ACSA), a 16-item self-report instrument (total score: 0-64), assessed withdrawal experiences. Mean ± SD ACSA scores and medians are presented for study completers. RESULTS: In the short-term efficacy studies, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine (pooled data) were 7.0 ± 7.60 (n = 275) and 4.9 ± 6.41 (n = 271), respectively, on the day of the last dose at week 12/early termination (ET) and 4.8 ± 6.82 (n = 234) and 5.5 ± 7.50 (n = 221) on day 7 after the last dose. In the maintenance-of-efficacy study, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine were 4.8 ± 6.67 (n = 44) and 4.7 ± 7.78 (n = 85) on the day of the last dose at week 38/ET and 3.9 ± 5.75 (n = 37) and 5.2 ± 7.93 (n = 71) on day 7 after the last dose. CONCLUSIONS: Study results suggest that abrupt lisdexamfetamine termination was not associated with amphetamine withdrawal symptoms at the exposure durations and therapeutic doses analyzed. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT01718483, NCT01718509, and NCT02009163.

What Is That? Innumerable Mysterious Densities Identified on Abdominal Imaging.

Radiopaque densities can be observed on imaging after the ingestion of either foreign bodies or some medications. Our case report discusses an 11-year-old boy with autism spectrum disorder and attention deficient disorder who presented to the emergency department because of concerns for constipation and dehydration. Incidentally, an abdominal x-ray showed numerous radiopaque densities throughout his intestines in addition to his constipation. He was admitted, and his home regimen was reviewed to attempt to identify a potential source for these radiopaque densities. This case presented an interesting teaching opportunity in the identification of the radiopaque densities and review of pharmacokinetics.

[New-onset trichotillomania during treatment with stimulant drugs. About two pediatric clinical cases]. / Tricotilomanía de nueva aparición durante el tratamiento con fármacos estimulantes. A propósito de dos casos clínicos pediátricos.

Stimulant drugs are commonly used in pediatric population in the treatment of attention deficit hyperactivity disorder, and their side effects are well described, however trichotillomania does not appear as one of them. In the literature we found some published cases of trichotillomania in relation to methylphenidate and dextroamphetamine. We present two cases of new-onset trichotillomania in children followed up in our center by attention deficit hyperactivity disorder and treated with psychostimulant drugs (methylphenidate and lisdexamfetamine), as a probable adverse effect of this treatment.

Los fármacos estimulantes se usan, habitualmente, en la población pediátrica para tratar el trastorno por déficit de atención e hiperactividad, y sus efectos secundarios están bien descritos. Sin embargo, la tricotilomanía no aparece como uno de ellos. En la literatura, hay algunos casos publicados de tricotilomanía en relación con la administración de metilfenidato y dextroanfetamina. Se presentan dos casos de tricotilomanía de nueva aparición en niños en seguimiento en nuestro Centro por déficit de atención e hiperactividad y en tratamiento con fármacos psicoestimulantes (metilfenidato y lisdexanfetamina), como probable efecto adverso de estos.