lisdexamfetamine-dimesylate and Attention-Deficit-Disorder-with-Hyperactivity

We sought to understand the effect of current treatments for attention deficit hyperactivity disorder (ADHD) on executive functioning deficits, which are often comorbid with ADHD, via a systematic analysis of adult ADHD treatment studies evaluating change in behavioral measures beyond the core symptoms of Diagnostic and Statistical Manual of Mental Disorders ADHD. The standardized mean difference for behavioral measures of executive functioning was determined from controlled trials of adults with ADHD and compared with effects on core ADHD symptoms. Several studies of atomoxetine revealed small to large standardized mean differences. Nonreplicated studies revealed small to medium effects for triple-bead mixed amphetamine salts, lisdexamfetamine, and forms of cognitive behavioral therapy. Proportional effect versus core ADHD symptoms ranged from 0.78 to 1.16 for atomoxetine, and from 0.65 to 1.44 across all the studies. ADHD treatments have effects on executive functioning behavior beyond core ADHD symptoms in adults. Clinicians can measure and treat this morbidity using available clinical tools.

Topics: Adult; Amphetamine; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Executive Function; Humans; Lisdexamfetamine Dimesylate

Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential.. To learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to April 29, 2021 in PubMed and MEDLINE using the following search terms: eating disorders, anorexia, bulimia, binge eating, stimulants, amphetamine, lisdexamfetamine, methylphenidate, and phentermine.. We propose that stimulant medications represent a novel avenue for future research based on the following: (a) the relationship between eating disorders and attention deficit/hyperactivity disorder (ADHD); (b) a neurobiological rationale; and (c) the current (but limited) evidence for stimulants as treatments for some eating disorders. Despite the possible benefits of such medications, there are also risks to consider such as medication misuse, adverse cardiovascular events, and reduction of appetite and pathological weight loss. With those risks in mind, we propose several directions for future research including: (a) randomized controlled trials to study stimulant treatment in those with bulimia nervosa (with guidance on strategies to mitigate risk); (b) examining stimulant treatment in conjunction with psychotherapy; (c) investigating the impact of stimulants on "loss of control" eating in youth with ADHD; and (d) exploring relevant neurobiological mechanisms. We also propose specific directions for exploring mediators and moderators in future clinical trials.. Although this line of investigation may be viewed as controversial by some in the field, we believe that the topic warrants careful consideration for future research.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic

Dysregulated emotional behavior occurs often in adults with ADHD. Analysis of clinical trials may guide clinical intervention and future research.. Controlled trials of adult ADHD measuring emotional behavior were included if another study offered a comparable analysis of the same treatment method. Standardized Mean Difference (SMD) of effects were calculated, and the size of effects for emotional and non-emotional ADHD behavior were compared.. 13 out of 14 studies of methylphenidate, atomoxetine, and lisdexamfetamine demonstrated significant improvement in emotional behavior measures, with small to high SMDs. The proportional effect on emotional versus non-emotional behavior ranged from 46% to 110% for methylphenidate, 56% to 129% for atomoxetine, and 36% to 96% for lisdexamfetamine.. Psychopharmacological treatments for ADHD are likely to improve emotional behavior, and available scales are sensitive to these effects. Studies dedicated to treatment of this domain of function can further refine clinical approaches.

Topics: Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Treatment Outcome

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.. 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')".. Most of the studies highlighted a longer T

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Expert Testimony; Lisdexamfetamine Dimesylate; Prodrugs; Treatment Outcome

Binge-eating disorder (BED) is a common psychiatric condition with adverse psychological and metabolic consequences. Lisdexamfetamine (LDX) is the only approved BED drug treatment. New drugs to treat BED are urgently needed.. A comprehensive review of published psychopathological, pharmacological and clinical findings.. The evidence supports the hypothesis that BED is an impulse control disorder with similarities to ADHD, including responsiveness to catecholaminergic drugs, for example LDX and dasotraline. The target product profile (TPP) of the ideal BED drug combines treating the psychopathological drivers of the disorder with an independent weight-loss effect. Drugs with proven efficacy in BED have a common pharmacology; they potentiate central noradrenergic and dopaminergic neurotransmission. Because of the overlap between pharmacotherapy in attention deficit hyperactivity disorder (ADHD) and BED, drug-candidates from diverse pharmacological classes, which have already failed in ADHD would also be predicted to fail if tested in BED. The failure in BED trials of drugs with diverse pharmacological mechanisms indicates many possible avenues for drug discovery can probably be discounted.. (1) The efficacy of drugs for BED is dependent on reducing its core psychopathologies of impulsivity, compulsivity and perseveration and by increasing cognitive control of eating. (2) The analysis revealed a large number of pharmacological mechanisms are unlikely to be productive in the search for effective new BED drugs. (3) The most promising areas for new treatments for BED are drugs, which augment noradrenergic and dopaminergic neurotransmission and/or those which are effective in ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Humans; Lisdexamfetamine Dimesylate; Neuropharmacology; Weight Loss

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.. 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.. 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.. 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.. PROSPERO no. CRD 42015026049.

Topics: Adult; Amphetamine; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Bupropion; Central Nervous System Stimulants; Dextroamphetamine; Drug-Related Side Effects and Adverse Reactions; Female; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Modafinil; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic

Emerging evidence supports a prevalence overlap between ADHD and bulimia nervosa/binge eating disorder. A high degree of ADHD symptoms may have a negative impact on recovery in eating disorders with loss of control over the eating, bingeing and purging. Screening/diagnostic evaluation of ADHD in all persons with loss of control over the eating/bingeing/purging eating disorders is required. For patients diagnosed with ADHD, treatment with stimulants can be tested and evaluated for both eating disorders and ADHD symptoms. While there is evidence that lisdexamfetamine reduces symptoms of binge eating disorder, rigorous studies evaluating ADHD treatment, including medication, for bulimia nervosa are still missing.

Topics: Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Feeding and Eating Disorders; Humans; Lisdexamfetamine Dimesylate

Psychostimulants are the first-line treatment in adults with attention-deficit hyperactivity disorder (ADHD). This meta-analysis aimed to evaluate the efficacy, acceptability, and tolerability of lisdexamfetamine (LDX), mixed amphetamine salts (MASs), modafinil (MDF), and methylphenidate (MPH) in comparison with placebo.. We systematically searched PubMed/MEDLINE and Clinicaltrials.gov in May 2016, along with CENTRAL and EU Clinical Trials Register in February 2016, for the randomized, double-blind, placebo-controlled, parallel-group clinical trials conducted on adults diagnosed with ADHD.. Substantial comorbidity, substance abuse or dependence, and nonpharmacological interventions represented grounds for exclusion. Published reports were the sole source for data extraction. Improvement in ADHD symptoms was the primary outcome. Random-effects model meta-analysis was applied to calculate the standardized mean difference (SMD) with 95% CIs.. The search retrieved 701 records, of which 20 studies were eligible for analysis. High effect size (expressed as SMD) in reducing ADHD symptoms was observed for LDX (-0.89; 95% CI = -1.09, -0.70), whereas MASs (-0.64; 95% CI = -0.83, -0.45) and MPH (-0.50; 95% CI = -0.58, -0.41) reduced symptoms moderately compared with placebo. No efficacy was shown for MDF (0.08; 95% CI; -0.18, 0.34). Relevance to Patient Care and Clinical Practice: In this meta-analysis, the efficacy, tolerability, and acceptability of psychostimulants were compared with that for placebo. Five of the included trials have not been evaluated in any of the previously published meta-analyses.. The results suggest that LDX has the largest effect size and has a promising potential for treating adults with ADHD.

Topics: Adult; Amphetamine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Salts; Treatment Outcome

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Europe; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Quality of Life; Treatment Outcome

Attention deficit hyperactivity disorder (ADHD) is a childhood-onset disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can persist into adulthood and can affects individuals' social and occupational functioning, as well as their quality of life and health. ADHD is frequently associated with other mental disorders such as substance use disorders and anxiety and affective disorders. Amphetamines are used to treat adults with ADHD, but uncertainties about their efficacy and safety remain.. To examine the efficacy and safety of amphetamines for adults with ADHD.. In August 2017, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and two trials registers, and we ran citation searches for included studies. We also contacted the corresponding authors of all included studies, other experts in the field, and the pharmaceutical company, Shire, and we searched the reference lists of retrieved studies and reviews for other published, unpublished, or ongoing studies. For each included study, we performed a citation search in Web of Science to identify any later studies that may have cited it.. We searched for randomised controlled trials comparing the efficacy of amphetamines (at any dose) for ADHD in adults aged 18 years and over against placebo or an active intervention.. Two review authors extracted data from each included study. We used the standardised mean difference (SMD) and the risk ratio (RR) to assess continuous and dichotomous outcomes, respectively. We conducted a stratified analysis to determine the influence of moderating variables. We assessed trials for risk of bias and drew a funnel plot to investigate the possibility of publication bias. We rated the quality of the evidence using the GRADE approach, which yielded high, moderate, low, or very low quality ratings based on evaluation of within-trial risk of bias, directness of evidence, heterogeneity of data; precision of effect estimates, and risk of publication bias.. We included 19 studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD (78.8%). Eighteen studies were conducted in the USA, and one study was conducted in both Canada and the USA. Ten were multi-site studies. All studies were placebo-controlled, and three also included an active comparator: guanfacine, modafinil, or paroxetine. Most studies had short-term follow-up and a mean study length of 5.3 weeks.We found no studies that had low risk of bias in all domains of the Cochrane 'Risk of bias' tool, mainly because amphetamines have powerful subjective effects that may reveal the assigned treatment, but also because we noted attrition bias, and because we could not rule out the possibility of a carry-over effect in studies that used a cross-over design.Sixteen studies were funded by the pharmaceutical industry, one study was publicly funded, and two studies did not report their funding sources.Amphetamines versus placeboSeverity of ADHD symptoms: we found low- to very low-quality evidence suggesting that amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD -0.90, 95% confidence interval (CI) -1.04 to -0.75; 13 studies, 2028 participants) and patients (SMD -0.51, 95% CI -0.75 to -0.28; six studies, 120 participants).Retention: overall, we found low-quality evidence suggesting that amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI 0.99 to 1.13; 17 studies, 2323 participants).Adverse events: we found that amphetamines were associated with an increased proportion of patients who withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies, 2409 participants).Type of amphetamine: we found differences between amphetamines for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine (SMD -1.06, 95% CI -1.26 to -0.85; seven studies, 896 participants; low-quality evidence) and MAS (SMD -0.80, 95% CI -0.93 to -0.66; five studies, 1083 participants; low-quality evidence) reduced the severity of ADHD symptoms. In contrast, we found no evidence to suggest that dexamphetamine reduced the severity of ADHD symptoms (SMD -0.24, 95% CI -0.80 to 0.32; one study, 49 participants; very low-quality evidence). In addition, all. Amphetamines improved the severity of ADHD symptoms, as assessed by clinicians or patients, in the short term but did not improve retention to treatment. Amphetamines were associated with higher attrition due to adverse events. The short duration of studies coupled with their restrictive inclusion criteria limits the external validity of these findings. Furthermore, none of the included studies had an overall low risk of bias. Overall, the evidence generated by this review is of low or very low quality.

Topics: Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobehavioral disorders. We carried out this comparison of multiple treatments based on sufficient data in attempt to evaluate the efficacy and safety of ADHD medication for children and adolescents. PubMed, Embase and the Cochrane Database were used to search for relevant articles. Changes in the ADHD Rating Scale (ADHD-RS) scores and the Conners' Parent Rating Scale-Revised (CPRS) scores were used as outcomes for efficacy. Withdrawals due to all-cause, adverse effects and lack of efficacy were defined as primary outcomes evaluating the safety of such medications. Both pair-wise and network meta-analyses were performed. Efficacy and safety of atomoxetine (ATX), bupropion (BUP), clonidine hydrochloride (CLON), guanfacine extended release (GXR), lisdexamfetamine dimesylate (LDX), and methylphenidate (MPH) were evaluated. LDX has the highest efficacy and a relatively lower rate of adverse effects compared to BUP, CLON and GXR. MPH has the lowest incidence rate of adverse effects and takes second place concerning ADHD-RS scores and third place concerning CPRS scores. ATX has the lowest incidence rate of all-cause withdrawals. The efficacy of ATX seems, however, to be lower than CLON, GXR, LDX and MPH. Adversely, BUP has the highest incidence rate of withdrawals and the second highest probability of causing adverse effects as well as lack of efficacy; therefore it should not be recommended as a treatment for ADHD.

Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Child; Clonidine; Dextroamphetamine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Treatment Outcome

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent neurodevelopmental disorders in the child population. Its treatment is complex and must include psychoeducational, environmental and pharmacological measures. In recent years, the main novelties as regards its pharmacological treatment have been the appearance of lisdexamphetamine and extended-release guanfacine.. The increase in the number of drugs available for the treatment of ADHD makes it possible to treat and cover a very wide range of different clinical situations. The purpose of this review is to perform an analysis of the literature on the two drugs.. The study determines the strong points of both treatments, with special attention given to their mechanism of action, their tolerability and their efficacy.. Extended-release guanfacine enables the professional to treat situations that are poorly covered by stimulants, such as children with irritability and tics, with a significant profile characterised by moderate efficacy and good tolerability and safety. The appearance of lisdexamphetamine has brought about a very important change because, according to the literature, it is a drug that, from the clinical point of view, is both complete and effective in improving the symptoms of ADHD. Moreover, it has a good safety profile.. Actualizacion en el tratamiento farmacologico del trastorno por deficit de atencion/hiperactividad: lisdexanfetamina y guanfacina de liberacion retardada.. Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo mas frecuentes en la poblacion infantil. Su tratamiento es complejo y debe incluir medidas psicoeducativas, ambientales y farmacologicas. En los ultimos años, las principales novedades respecto a su tratamiento farmacologico son la aparicion de la lisdexanfetamina y la guanfacina de liberacion retardada. Objetivo. El aumento del numero de farmacos disponibles para el tratamiento del TDAH permite tratar y cubrir situaciones clinicas muy diversas. El proposito de la presente revision es realizar un analisis de la bibliografia sobre ambos farmacos. Desarrollo. Se establecen los puntos fuertes de ambos tratamientos, atendiendo especialmente a su mecanismo de accion, a su tolerabilidad y a su eficacia. Conclusiones. La guanfacina de liberacion retardada permite tratar situaciones escasamente cubiertas con los estimulantes, tales como los niños con irritabilidad y tics, con un perfil significativo de moderada eficacia y una buena tolerabilidad y seguridad. La aparicion de la lisdexanfetamina ha supuesto un cambio muy importante porque, segun la bibliografia, se trataria de un farmaco completo y efectivo, desde el punto de vista clinico, para mejorar los sintomas del TDAH. Ademas, posee un buen perfil de seguridad.

Topics: Adrenergic alpha-2 Receptor Agonists; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Guanfacine; Humans; Lisdexamfetamine Dimesylate

Adult Attention Deficit Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition associated with high disability and frequent comorbidity. Current standard pharmacotherapy (methylphenidate and atomoxetine) improves ADHD symptoms in the short-term, but poor data were published about long-term treatment. In addition a number of patients present partial or no response to methylphenidate and atomoxetine. Research into the main database sources has been conducted to obtain an overview of alternative pharmacological approaches in adult ADHD patients. Among alternative compounds, amphetamines (mixed amphetamine salts and lisdexamfetamine) have the most robust evidence of efficacy, but they may be associated with serious side effects (e.g. psychotic symptoms or hypertension). Antidepressants, particularly those acting as noradrenaline or dopamine enhancers, have evidence of efficacy, but they should be avoided in patients with comorbid bipolar disorder. Finally metadoxine and lithium may be particularly suitable in case of comorbid alcohol misuse or bipolar disorder.

Topics: Adrenergic alpha-Agonists; Adult; Amphetamines; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Bridged Bicyclo Compounds, Heterocyclic; Bupropion; Central Nervous System Stimulants; Desipramine; Dopamine Agents; Droxidopa; Drug Combinations; Duloxetine Hydrochloride; Guanfacine; Histamine Agents; Humans; Lisdexamfetamine Dimesylate; Lithium Compounds; Lobeline; Mecamylamine; Memantine; Modafinil; Morpholines; Nicotinic Agonists; Nicotinic Antagonists; Nomifensine; Paroxetine; Pyridines; Pyridoxine; Pyrrolidonecarboxylic Acid; Quinazolinones; Reboxetine; Venlafaxine Hydrochloride; Wakefulness-Promoting Agents

Lisdexamfetamine dimesylate (LDX) is a long-acting d-amphetamine prodrug used to treat attention-deficit/hyperactivity disorder (ADHD) in children, adolescents and adults. LDX is hydrolysed in the blood to yield d-amphetamine, and the pharmacokinetic profile of d-amphetamine following oral administration of LDX has a lower maximum plasma concentration (Cmax), extended time to Cmax (Tmax) and lower inter- and intra-individual variability in exposure compared with the pharmacokinetic profile of an equivalent dose of immediate-release (IR) d-amphetamine. The therapeutic action of LDX extends to at least 13 h post-dose in children and 14 h post-dose in adults, longer than that reported for any other long-acting formulation. Drug-liking scores for LDX are lower than for an equivalent dose of IR d-amphetamine, which may result from the reduced euphorigenic potential associated with its pharmacokinetic profile. These pharmacokinetic and pharmacodynamic characteristics of LDX may be beneficial in the management of symptoms in children, adolescents and adults with ADHD.

Topics: Administration, Oral; Adolescent; Adult; Amphetamine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Drug Delivery Systems; Humans; Lisdexamfetamine Dimesylate; Male; Prodrugs; Treatment Outcome

Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting amfetamine prodrug with a convenient once-daily oral regimen that offers the potential for improved adherence and reduced abuse compared with short-acting preparations of amfetamines. Lisdexamfetamine (as Elvanse Adult(®); Tyvense Adult™) has been approved for use in adults with attention-deficit hyperactivity disorder (ADHD) under the EU decentralization procedure, with the first approvals in the UK, Sweden and Denmark. This approval reflects the results of three short-term trials in adults with ADHD in which fixed- or flexible-dose lisdexamfetamine produced significantly greater improvements than placebo in ADHD symptoms, overall functioning, executive functioning (including in patients with significant pre-existing impairment) and quality of life. Of note, a post hoc analysis of one of these studies suggested that the response to lisdexamfetamine was generally similar in treatment-naïve patients and those who had already received-and not responded satisfactorily to-previous ADHD therapies, including methylphenidate (MPH). Two further studies demonstrated the longer-term effectiveness of flexible-dose lisdexamfetamine in reducing ADHD symptoms, albeit maintenance of efficacy required ongoing treatment with the drug. Lisdexamfetamine was generally well tolerated in clinical trials, with an adverse event profile typical of that reported for other long-acting stimulants. Head-to-head comparisons with other long-acting agents, notably MPH and atomoxetine, are lacking. Nonetheless, on the basis of the available data, lisdexamfetamine provides a useful alternative option for the treatment of adults with ADHD, including those who have not responded adequately to previous ADHD therapies, including MPH.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate

Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms. The in vivo pharmacodynamics of LDX is the same as that of its active product d-AMPH, although there are a few qualitative and quantitative differences due to pharmacokinetics. Due to the specific pharmacokinetics of the long-acting stimulants, this article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug. The Medline/Pubmed, Science Direct and Biblioteca Virtual em Saúde (Lilacs and Ibecs) (2007-2016) databases were searched for articles and their list of references. As for basic pharmacokinetics studies, since LDX is a newly developed medication, there are few results concerning biotransformation, distribution and the use of different biological matrices for analysis. This is the first robust review on this topic, gathering data from all clinical pharmacokinetics studies available in the literature. The particular pharmacokinetics of LDX plays a major role in studying this pro-drug, since this knowledge was essential to understand some reports on clinical effects in literature, e.g. the small likelihood of reducing the effect by interactions, the effect of long duration use and the still questionable reduction of the potential for abuse. In general the already well-known pharmacokinetic properties of amphetamine make LDX relatively predictable, simplifying the use of LDX in clinical practice.

Topics: Attention Deficit Disorder with Hyperactivity; Biotransformation; Humans; Lisdexamfetamine Dimesylate; Prodrugs

Therapeutic goals for chronic mental disorders like major depressive disorder (MDD) and schizophrenia have evolved in parallel with the growing medical knowledge about the course and treatment of these disorders. Although the knowledge base regarding the clinical course of ADHD, a chronic psychiatric disorder, has evolved beyond symptomatic improvement and short-term treatment response, long-term goals, such as functional remission, have not yet been clearly defined.. A PubMed literature search was conducted to investigate the therapeutic goals of pharmacologic treatment referenced in the published literature from January 1998 through February 2010 using the following commonly used ADHD treatments as keywords: amphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine, and clonidine. This search was then combined with an additional search that included the following outcome keywords: remission, relapse, remit, response, normal, normalization, recovery, and effectiveness.. Our search identified 102 publications. The majority (88.2% [90/102]) of these contained predefined criteria for treatment response. Predefined criteria for normalization and remission and/or relapse were presented in 4.9% (5/102), 12.7% (13/102), and 3.9% (4/102) of publications, respectively. There was a lack of consistency between the instruments used to measure outcomes as well as the criteria used to define treatment response, normalization, and remission as well as relapse.. The therapeutic goals in treating ADHD should address optimal treatment outcomes that go beyond modest reductions of ADHD symptoms to include syndromatic, symptomatic, and functional remission. Future work should focus on reliable and valid tools to measure these outcomes in the clinical trial setting.

Topics: Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Goals; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Propylamines; Quality of Health Care; Treatment Outcome

There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data.. A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design.. Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses.. This model predicts that LDX may have a large treatment effect size in European adults with ADHD.

Topics: Adult; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Europe; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Regression Analysis; Treatment Outcome

There is a lack of comparative effectiveness research among attention deficit hyperactivity disorder (ADHD) drugs in terms of efficacy and acceptability, where bupropion is compared with atomoxetine, lisdexamfetamine and methylphenidate. The main aim of this work was to compare the efficacy and acceptability of these drugs in children and adolescents using a metaanalysis.. A literature search was conducted to identify double-blind, placebo-controlled, noncrossover studies of ADHD. PubMed/Medline and Clinicaltrials.gov were searched. Comparative drug efficacy to placebo was calculated based on the standardized mean difference (SMD), while the comparative drug acceptability (all cause discontinuation) to placebo was estimated on the odds ratio (OR).. In total 28 trials were included in the meta-analysis. Efficacy in reducing ADHD symptoms compared to placebo was small for bupropion (SMD=-0.32, 95% CI; -0.69, 0.05), while modest efficacy was shown for atomoxetine (SMD=-0.68, 95% CI; -0.76, -0.59) and methylphenidate (SMD=-0.75, 95% CI; -0.98, -0.52) and high efficacy was observed for lisdexamfetamine (SMD=-1.28, 95% CI; -1.84, -0.71). Compared to placebo treatment discontinuation was statistically significantly lower for methylphenidate (OR=0.35, 95% CI; 0.24, 0.52), while it was not significantly different for atomoxetine (OR=0.91, 95% CI; 0.66, 1.24), lisdexamfetamine (OR=0.60, 95% CI, 0.22, 1.65), and bupropion (OR=1.64, 95% CI; 0.5, 5.43).. The heterogeneity was high, except in atomoxetine trials. The crossover studies were excluded. The effect sizes at specific time points were not computed. Studies with comorbid conditions, except those reporting on oppositional defiant disorder, were also excluded. All studies involving MPH were combined.. The results suggest that lisdexamfetamine has the best benefit risk balance and has promising potential for treating children and adolescents with ADHD. More research is needed for a better clinical evaluation of bupropion.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Bupropion; Central Nervous System Stimulants; Child; Comparative Effectiveness Research; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Patient Acceptance of Health Care; Propylamines; Randomized Controlled Trials as Topic; Treatment Outcome

Several studies have shown that lisdexamfetamine (LDX) is efficacious in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).. Aims of this study were to systematically review the efficacy, acceptability, and tolerability of LDX in child and adolescent ADHD. Any randomized controlled trials (RCTs) of LDX versus placebo carried out in children and adolescents with ADHD were included.. The searches of the SCOPUS, MEDLINE, CINAHL and Cochrane Controlled Trials Register were performed in September 2014. Additional searches in the ClinicalTrials. gov and EU Clinical Trials Register database were conducted.. This review included all RCTs of LDX versus placebo which were carried out in children and adolescents up to 18 years old. Additionally, the included studies must have reported the final outcomes of: i) severity of ADHD symptoms with standardized scales, ii) rates of improvement, iii) rates of discontinuation. To be more thorough, the languages of such RCTs were not limited.. The abstracts from databases were inspected and the full text versions of relevant trials were examined and extracted for important outcomes. The efficacious measurements included either the pooled mean end-point or changed scores of ADHD rating scales, and the rate of improvement. Acceptability and tolerability were measured by the pooled overall discontinuation rate and the pooled discontinuation rate due to adverse events, respectively. A random effect model technique was utilized to synthesize the mean differences (either standardized mean differences or weighted mean differences) and relative risks (RRs) with 95% confidence intervals (CIs).. A total of 1,016 children and adolescents with ADHD were included. The dosage of LDX was 30 to 70 mg/day. The pooled mean change scores of LDX-treated group was significantly greater than that of the placebo (weighted mean difference [95% CI] of -15.20 [-19.95, -10.46], I (2)=94%). The pooled improvement rate of the LDX-treated group was also significantly higher than that of the placebo (RR [95% CI] of 0.34 [0.24, 0.47], I (2)=80%). The pooled overall discontinuation rate between the two groups was not significantly different (RR [95% CI] of 0.78 [0.46, 1.31], I (2)=63%). Similarly, the pooled discontinuation rate due to adverse events between the two groups showed no significant difference (RR [95% CI] of 1.99 [0.70, 5.64], I (2)=0%).. The number of included studies was limited (five RCTs).. According to the present review, LDX was effective and well-tolerated in the treatment of child and adolescent ADHD. Unfortunately, the acceptability of LDX was not better than the placebo. Since the number of included studies was limited, the outcome from this review should be carefully interpreted and considered as preliminary. Further studies, therefore, should be conducted to confirm these findings.. Lisdexamfetamine is an efficacious stimulant for treating child and adolescent ADHD.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Drug Tolerance; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic

Among young people up to 18 years of age, approximately 5% have attention deficit hyperactivity disorder (ADHD), many of whom have symptoms persisting into adulthood. ADHD is associated with increased risk of co-morbid psychiatric disorders, including substance misuse. Many will be prescribed medication, namely methylphenidate, atomoxetine, dexamphetamine and lisdexamfetamine. If so, it is important to know if interactions exist and if they are potentially toxic.. Three databases (Medline, EMBASE and PsychINFO) from a 22 year period (1992 - June 2014) were searched systematically. Key search terms included alcohol, substance related disorders, methylphenidate, atomoxetine, dexamphetamine, lisdexamfetamine, and death, which identified 493 citations (344 after removal of duplicates). The eligibility of each study was assessed jointly by two investigators, leaving 20 relevant articles.. We identified only a minimal increase in side-effects when ADHD medication (therapeutic doses) was taken with alcohol. None of the reviewed studies showed severe sequelae among those who had overdosed on ADHD medication and other coingestants, including alcohol.. The numbers across all the papers studied remain too low to exclude uncommon effects. Also, studies of combined effects with novel psychoactive substances have not yet appeared in the literature. Nevertheless, no serious sequelae were identified from combining ADHD medication with alcohol/illicit substances from the pre-novel psychoactive substance era.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Alcohol Drinking; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Drug Interactions; Humans; Illicit Drugs; Lisdexamfetamine Dimesylate; Methylphenidate; Substance-Related Disorders

Systematically review and synthesize the clinical evidence of treatments for attention deficit hyperactivity disorder (ADHD) by indirectly comparing established treatments in the UK with a drug recently approved in Europe (lisdexamfetamine [LDX]).. children and adolescents.. Europe. Comparators: methylphenidate (MPH), atomoxetine (ATX), and dexamphetamine (DEX). Electronic databases and relevant conference proceedings were searched for randomized, controlled clinical trials evaluating efficacy and safety of at least one of the comparators and LDX. Quality assessments for each included trial were performed using criteria recommended by the Centre for Reviews and Dissemination. Network meta-analysis methods for dichotomous outcomes were employed to evaluate treatment efficacy.. Response, as defined by either a reduction from baseline of at least 25% in the ADHD Rating Scale [ADHD-RS] total score or, separately, as assessed on the Clinical Global Impression-Improvement [CGI-I] scale, and safety (all-cause withdrawals and withdrawal due to adverse events).. The systematic review found 32 trials for the meta-analysis, including data on LDX, ATX, and different formulations of MPH. No trials for DEX meeting the inclusion criteria were found. Sufficient data were identified for each outcome: ADHD-RS, 16 trials; CGI-I, 20 trials; all-cause withdrawals, 28 trials; and withdrawals due to adverse events, 27 trials. The relative probability of treatment response for CGI-I (95% confidence intervals [CI]) for ATX versus LDX was 0.65 (0.53-0.78); for long-acting MPH versus LDX, 0.82 (0.69-0.97); for intermediate release MPH versus LDX, 0.51 (0.40-0.65); and for short-acting MPH versus LDX, 0.62 (0.51-0.76). The relative probabilities of ADHD-RS treatment response also favored LDX.. For the treatment of ADHD, the synthesis of efficacy data showed statistically significant better probabilities of response with LDX than for formulations of MPH or ATX. The analysis of safety data proved inconclusive due to low event rates. These results may be limited by the studies included, which only investigated the short-term efficacy of medications in patients without comorbid disorders.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dopamine Uptake Inhibitors; Europe; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Models, Statistical; Propylamines; Treatment Outcome

Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD).. A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]).. In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX.. The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials, Phase III as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Randomized Controlled Trials as Topic; Time Factors

Lisdexamfetamine dimesylate (LDX) is a long-acting oral prodrug stimulant. It is inactive until enzymatically hydrolyzed in the blood to active D-amphetamine. The pharmacological action of this compound involves blocking norepinephrine (NE) and dopamine reuptake into presynaptic neurons and promoting the release of NE and dopamine into the extraneuronal space. LDX has been approved for treating ADHD, which is the most common psychiatric disorder in children and adolescents. Also, LDX has been proposed for other psychiatric conditions related with dopaminergic and NE CNS. LDX is the first long-acting oral prodrug indicated for the treatment of ADHD in children (6-12 years), adolescents (13-17 years) and in adults in the USA and Canada, whereas, in Europe, LDX is licensed in several countries for the treatment of children and adolescents with ADHD who have had a clinically inadequate response to methylphenidate. This article covers the most important pharmacological aspects of LDX as well as data on the efficacy, tolerability and safety of this long-acting amphetamine prodrug collected from clinical studies recently published in the literature.

Topics: Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Mental Disorders

Recent studies have promised that lisdexamfetamine (LDX) is effective in the treatment of adults with attention-deficit hyperactivity disorder (ADHD).. This systematic review was undertaken to summarize LDX efficacy, acceptability, and tolerability in adult ADHD. All randomized controlled trials (RCTs) of lisdexamfetamine compared with placebo were included for synthesis. Clinical trials published between January 1991 and January 2014 were evaluated.. The database of MEDLINE(®), EMBASE™, CINAHL(®), PsycINFO(®) and Cochrane Controlled Trials Register were searched in January 2014. Studies were also searched in ClinicalTrials.gov and the EU Clinical Trials Register database. Study eligibility criteria, participants, and interventions were considered. All RCTs of LDX vs placebo reporting final results of: 1) severity of ADHD symptoms and executive function deficit, 2) response or remission rates, 3) overall discontinuation rate, or 4) discontinuation rate due to adverse events were included. The language of the papers was not restricted. All abstracts of studies gathered from the database were examined. After excluding irrelevant trials, the full text version of relevant studies were assessed and extracted for outcomes of interest. Examination of risks of bias, based on the Cochrane bias assessment, was carried out. The efficacy outcomes consisted of the mean end point or change scores for ADHD rating scales, the response rate, and the remission rate. The overall discontinuation rate and the discontinuation rate due to adverse events were measured for acceptability and tolerability, respectively. A random effect model was applied for the synthesis of relative risks (RRs), and weighted mean differences or standardized mean differences (SMDs) with 95% confidence intervals (CIs).. A total of 806 final study or safety participants were included. The dosage of lisdexamfetamine was 30 to 70 mg/day. The pooled mean scores of mean change and mean end point scores between LDX- and placebo-treated groups also had a significant difference (SMD [95% CI] of -0.97 [-1.15, -0.78], I(2)=18%). The pooled response rates for adult ADHD between the two groups had a significant difference (RR [95% CI] of 1.99 [1.50, 2.63], I(2)=0%). Based on the Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A), the pooled end point mean scores for the Global Executive Composite (GEC) for the LDX-treated groups was greater than that of placebo-treated groups (MD [95% CI] of -9.20 [-14.11, -4.29], I(2)=34%). The pooled overall discontinuation rates between the two groups had no significant difference (RR [95% CI] of 0.82 [0.59, 1.14], I(2)=0%). Similarly, the pooled discontinuation rates due to adverse events between the two groups was not significantly different (RR [95% CI] of 1.77 [0.71, 4.40], I(2)=0%).. The number of included studies was limited (five RCTs), but based on this meta-analysis, LDX is efficacious and well tolerated in the treatment of adult ADHD. Additionally, it also improved the executive function deficits in this population. However, its acceptability is no higher than placebo. These findings should be carefully interpreted and considered as preliminary outcomes. To confirm these results, further studies are warranted. LDX is a viable alternative psychostimulant for adult ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Databases, Factual; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Placebos; Registries

Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

Topics: Adolescent; Adult; Amphetamine; Amphetamine-Related Disorders; Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Drug Design; Humans; Lisdexamfetamine Dimesylate; Narcolepsy; Prodrugs

Individuals with attention-deficit/hyperactivity disorder (ADHD) show pervasive impairments across family, peer, and school or work functioning that may extend throughout the day. Psychostimulants are highly effective medications for the treatment of ADHD, and the development of long-acting stimulant formulations has greatly expanded the treatment options for individuals with ADHD. Strategies for the formulation of long-acting stimulants include the combination of immediate-release and delayed-release beads, and an osmotic-release oral system. A recent development is the availability of the first prodrug stimulant, lisdexamfetamine dimesylate (LDX). LDX itself is inactive but is cleaved enzymatically, primarily in the bloodstream, to release d-amphetamine (d-AMP). Several clinical trials have demonstrated that long-acting stimulants are effective in reducing ADHD symptoms compared with placebo. Analog classroom and simulated adult workplace environment studies have shown that long-acting stimulants produce symptom reduction for at least 12 h. Long-acting stimulants exhibit similar tolerability and safety profiles to short-acting equivalents. While variations in gastric pH and motility can alter the availability and absorption of stimulants released from long-acting formulations, the systemic exposure to d-AMP following LDX administration is unlikely to be affected by gastrointestinal conditions. Long-acting formulations may also improve adherence and lower abuse potential compared with their short-acting counterparts. The development of long-acting stimulants provides physicians with an increased range of medication options to help tailor treatment for individuals with ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Medication Adherence; Prodrugs

The efficacy and safety of stimulants for the pharmacologic management of attention deficit hyperactivity disorder (ADHD) is well documented. The US Food and Drug Administration approval of additional classes of medication even within stimulant treatments expands the prescribing options for practitioners. The focus of this paper is the prodrug amphetamine stimulant, lisdexamfetamine (LDX) , which is an example of such an agent with a novel delivery system.. This review covers the proof-of-concept and later studies of LDX to describe its use to treat ADHD in pediatric and adult populations. A literature search and review of LDX were carried out using the PubMed database up to August 2012.. Clinical studies of LDX in children and adults with ADHD demonstrate its tolerability and its efficacy in reducing ADHD symptoms. Future research should be less restrictive in order to address some of the unmet needs in ADHD treatment. The inclusion of patients with ADHD and co-occurring mental health disorders and/or medical conditions is typically not studied in clinical trials nor is the prior ADHD treatment exposure of study participants. The preschool age population also is understudied in recently approved ADHD treatments such as LDX. Finally, how to approach the treatment of participants or first-degree relatives with a medical history or presence of substance use disorder presents an ongoing clinical challenge.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Middle Aged; Pediatrics; Practice Guidelines as Topic; Randomized Controlled Trials as Topic

Medication is an important element of therapeutic strategies for ADHD. While medications for ADHD are generally well-tolerated, there are common, although less severe, as well as rare but severe adverse events AEs during treatment with ADHD drugs. The aim of this review is to provide evidence- and expert-based guidance concerning the management of (AEs) with medications for ADHD.. For ease of use by practitioners and clinicians, the article is organized in a simple question and answer format regarding the prevalence and management of the most common AEs. Answers were based on empirical evidence from studies (preferably meta-analyses or systematic reviews) retrieved in PubMed, Ovid, EMBASE and Web of Knowledge through 30 June 2012. When no empirical evidence was available, expert consensus of the members of the European ADHD Guidelines Group is provided. The evidence-level of the management recommendations was based on the SIGN grading system.. The review covers monitoring and management strategies of loss of appetite and growth delay, cardiovascular risks, sleep disturbance, tics, substance misuse/abuse, seizures, suicidal thoughts/behaviours and psychotic symptoms.. Most AEs during treatment with drugs for ADHD are manageable and most of the times it is not necessary to stop medication, so that patients with ADHD may continue to benefit from the effectiveness of pharmacological treatment.

Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Body Size; Cardiovascular Diseases; Central Nervous System Stimulants; Child; Clonidine; Dextroamphetamine; Growth Disorders; Guanfacine; Heart Rate; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Propylamines; Psychoses, Substance-Induced; Seizures; Sleep Wake Disorders; Substance-Related Disorders; Suicide Prevention; Tic Disorders; Treatment Outcome

An earlier meta-analysis of pediatric clinical trials indicated that lisdexamfetamine dimesylate (LDX) had a greater effect size than other stimulant medications. This work tested the hypothesis that the apparent increased efficacy was artifactual.. The authors assessed two potential artifacts: an unusually high precision of measurement and an unusually low placebo effect. The authors evaluated generalizability from children of adults.. The LDX effect sizes for children were significantly larger than the pooled stimulant effect sizes from studies using the same outcome measures. However, although no other individual stimulant study had an effect size greater than LDX, there was overlap between the 95% confidence intervals for some of these studies and the LDX study. The high LDX effect sizes were not due measurement or placebo effect artifacts. LDX effect sizes for adults were not larger than the stimulant effect sizes from other studies.. The high LDX effect size for children could not attributed to measurement artifacts. The superiority of LDX in the pediatric clinical trial reflected the greater efficacy of amphetamine products, compared with methylphenidate products but required replication in children because (a) the results were based on only one trial of LDX in children, and (b) the finding did not generalize to adults.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Treatment Outcome

The current pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) is mainly based on the stimulant methylphenidate and to a small extent on amphetamines which are not approved in Germany. The only approved non-stimulant so far is atomoxetin (Strattera®), a norepinephrine reuptake inhibitor. There is no approved pharmacotherapy for adults. The aim of the available medication is a reduction of impulsivity, hyperactivity, and attention deficits. Neurobiological correlates of these effects are still not fully understood, however, a functional implication of dopaminergic and noradrenergic systems is known. To date there is no disease-modifying therapy. The currently available substances have limitations due to the short half-life of stimulants, the unknown pathomechanisms, and the use of stimulants in developing brains with possible long-term side-effects. Moreover, the abuse potential of stimulants is still controversially discussed. The recently developed Lisdexamfetamin and SPD-465 have stimulant effects, too. A number of different developmental substances in preclinical and clinical phases show other mechanisms: SPD-503 represents an α(2)A-adrenozeptoragonist, ABT-089 and ABT-418 have partial agonistic effects to the α(4)β(2)-subtype of nicotinic acetylcholinreceptors, CX-717, -1739, -1942 and -1796 are glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor agonists and PF-3 654 746 exhibits antagonistic properties to histaminergic H(3)-receptors. The α(2)A-adrenoceptor-agonist Guanfacine (Intuniv®) and the hepatic metabolised amphetamine prodrug Lisdexamfetamin (Vyvanse®) are yet approved for ADHD treatment in the USA. The aim of this review is to summarise established pharmacological treatment options and the stage of development of upcoming symptomatic stimulant and non-stimulant substances in ADHD therapy.

Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Central Nervous System Stimulants; Child; Dextroamphetamine; Fatty Acids, Omega-3; Guanfacine; Histamine Agonists; Humans; Isoxazoles; Lisdexamfetamine Dimesylate; Memantine; Methylphenidate; Modafinil; Off-Label Use; Propylamines; Pyridines; Pyrrolidines; Receptors, AMPA

ADHD is a common neurobehavioral disorder characterized by significant impairment in attention, hyperactivity and impulsivity. Symptoms begin in childhood and can persist into adulthood. Current data suggest that abnormal functioning of the prefrontal cortex, cortical and subcortical regions of the brain have roles in ADHD. All currently approved drugs used to treat ADHD enhance dopamine and norepinephrine signals in these regions. Lisdexamfetamine dimesylate (LDX) is a long-acting amphetamine prodrug indicated for the treatment of ADHD and has been shown to be effective in children, adolescents and adults. The prodrug properties of LDX make it a desirable treatment because of its long duration of effect, and low intrasubject and intersubject pharmacokinetic variability, and attenuated response on measures of abuse liability when compared with immediate-release amphetamine. However, LDX is still classified as a controlled substance. In this article, the pharmacokinetic parameters and efficacy and safety of LDX are reviewed.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate

To review the latest data available concerning the diagnosis and treatment of adults with attention deficit hyper-activity disorder (ADHD).. A number of different instruments for evaluating ADHD have been adapted to the adult patient and allow a reliable diagnosis of the disorder to be reached. Semi-structured interviews, like the Diagnostisch Interview Voor ADHD 2.0 (DIVA), simplify the task of performing a rigorous evaluation of both the symptoms of the disorder in adulthood and the dysfunctions generated by ADHD. Quick screening instruments that allow better detection of ADHD in adults, such as the Adult Self-Report Scale 1.1 (ASRS), have been validated. In recent years, there has been a notable increase in the number of studies focused on ADHD in adults and that research has provided solid data regarding the safety and effectiveness of different treatments. According to the recommendations of the European Consensus statement by the European Network Adult ADHD, the treatment ought to be multimodal, which means combining pharmacological interventions with psychological and psychosocial ones. Methylphenidate displays a high degree of effectiveness and safety in the treatment of adults at doses of around 1 mg/kg/day. Amphetamines, such as lisdexamphetamine, have also proved to be effective in the treatment of adults with ADHD. Among non-stimulant treatments, atomoxetine has proved to be effective and safe in adults in doses of about 80-100 mg/day. Excellent studies have been conducted on the cognitive-behavioural treatment of adults with ADHD, the results of which highlight its effectiveness in both the short and the long term.

Topics: Adult; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Automobile Driving; Behavior Therapy; Bupropion; Central Nervous System Stimulants; Combined Modality Therapy; Comorbidity; Dextroamphetamine; Diagnostic Self Evaluation; Educational Status; Female; Humans; Interpersonal Relations; Interview, Psychological; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Neuropsychological Tests; Occupations; Propylamines; Quality of Life; Severity of Illness Index; Symptom Assessment

Attention-deficit hyperactivity disorder (ADHD) is associated with substantial functional, clinical and economic burdens. It is among the most common psychiatric disorders in children and adolescents, and often persists into adulthood. Both medication and psychosocial interventions are recommended for the treatment of ADHD. However, ADHD treatment practices vary considerably, depending on medication availability, reimbursement and the evolution of clinical practice in each country. In Europe, stimulants and atomoxetine are widely available medications for the treatment of ADHD, whereas in the US approved treatment options also include extended-release formulations of clonidine and guanfacine. Lisdexamfetamine dimesylate (lisdexamfetamine) is a long-acting, prodrug formulation of dexamfetamine. It is currently licensed in the US, Canada and Brazil, and is undergoing phase III studies in Europe. We performed a PubMed/MEDLINE search looking for recent (2005-2012) scientific papers regarding the pharmacokinetics, pharmacodynamics, efficacy and safety of lisdexamfetamine. The lisdexamfetamine molecule is therapeutically inactive and is enzymatically hydrolysed, primarily in the blood, to the active dexamfetamine. This conversion is unaffected by gastrointestinal pH and variations in normal transit times. Lisdexamfetamine was developed with the goal of providing an extended duration of effect that is consistent throughout the day. Clinical trials have demonstrated robust clinical efficacy of lisdexamfetamine in the treatment of children, adolescents and adults with ADHD with dose-dependent improvements in the core symptoms of ADHD. Studies have further shown that the duration of action of lisdexamfetamine continues for 13 hours post-dosing in children and for 14 hours in adults. The tolerability profile of lisdexamfetamine is consistent with those of other stimulant medications, with decreased appetite, insomnia, abdominal pain and irritability among the more frequent treatment-emergent adverse events, most of which are mild to moderate in intensity and transient in nature. There are currently no parallel-group, head-to-head trial data comparing the efficacy and safety of lisdexamfetamine with other medications for ADHD. However, the available data, including a large effect size and consistent plasma concentrations throughout the day, suggest that lisdexamfetamine is a useful treatment option for patients with ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic; Treatment Outcome

Attention-deficit/hyperactivity disorder (ADHD) is a highly genetic neuropsychiatric disorder that can cause impairment at school, work, home, and in social relationships. Once considered a childhood disorder, as many as 65% of children with ADHD continue to exhibit symptoms into adulthood. While a mainstay of ADHD patient care, immediate-release stimulant use has been constrained by concerns about safety, tolerability, and issues related to nonmedical use and abuse. These concerns have prompted interest in developing modified versions or new delivery systems for stimulants. Prodrugs have been used in pharmaceutical development to optimize delivery of an active drug or to minimize toxicity. Prodrugs are pharmacologically inactive compounds that require in vivo conversion to release therapeutically active medications. Lisdexamfetamine dimesylate (LDX) is an inactive, water-soluble prodrug in which d-amphetamine is bonded to l-lysine, a naturally occurring amino acid. After oral ingestion, LDX is metabolized into l-lysine and active d-amphetamine. This review of LDX presents the efficacy, safety, and pharmacokinetic profile of this novel stimulant medication, and is intended to help clinicians understand its role in treating children and adults with ADHD.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Treatment Outcome

To examine duration of efficacy in long-acting stimulant treatment of attention-deficit/hyperactivity disorder (ADHD) in clinical trials using analog classroom protocols.. Published reports of clinical trials examining duration of medication efficacy using analog classroom protocols were identified in a systematic literature search of PubMed, BIOSYS, and EMBASE, through June 2009 using combinations of terms: attention-deficit/hyperactivity disorder, ADHD, attention-deficit disorder with hyperactivity, stimulant, methylphenidate (MPH), amphetamine, laboratory school or classroom, analog classroom, math test, and Permanent Product Measure of Performance (PERMP). Reports of short-acting, nonoral or nonstimulant formulations, or inadequate data on duration of efficacy were excluded.. Main outcomes examined were PERMP scores for number of math problems attempted (PERMP-A) and correctly answered (PERMP-C) based on a standard 10-minute math test given at regular intervals during the postdose period.. Fifteen trials were included in the analysis. All except one trial in adults (18-55 years) were conducted in children with ADHD (6-15 years) and employed randomized, double- or single-blind, placebo-controlled designs. Duration of efficacy, based on PERMP-A/-C scores (vs. placebo), ranged from 8 hours with long-acting MPH to 14 hours with lisdexamfetamine dimesylate; most formulations exerted therapeutic effects for 12 hours after a single morning dose. Duration of efficacy assessment may be limited by duration of observation (12 hours postdose for most studies). Outcomes may have been influenced by differences in study designs, population characteristics, lack of comparable, equivalent dosages of different extended-release stimulants, and limited ability to extrapolate safety and tolerability from short-term studies to long-term clinical use. Results from cross-study comparisons must be interpreted with caution.. Most long-acting stimulants exerted beneficial effects on ADHD symptoms for up to 12 hours as measured by the PERMP; the longest duration of efficacy versus placebo was seen with lisdexamfetamine dimesylate (14 hours postdose).

Topics: Administration, Oral; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials as Topic; Dextroamphetamine; Drug Administration Schedule; Humans; Lisdexamfetamine Dimesylate; Time Factors

Attention deficit/hyperactivity disorder (ADHD), a prevalent disorder in children and adults, presents a substantial societal burden in both monetary cost and human suffering. Characterized by significant difficulties in maintaining attention, completing tasks, motor control, and appropriate social engagement, the disorder begins early in life and results in significant impairment across domains of functioning, including social, educational, and occupational achievement. The condition also carries heightened risk of substance use and dependence, and criminal activity. Pharmacologic treatment is a key component of ADHD management and has been found to be cost effective and generally well tolerated. However, despite increasing options for medication therapy, community management of ADHD is suboptimal. This review assesses current research on lisdexamfetamine dimesylate (LDX), a relatively recent addition to the range of treatment options.. This review summarizes peer-reviewed literature on LDX published 2003 - 2010.. The reader will gain insight into the efficacy and safety of LDX in the treatment of ADHD, and its place in the clinical armamentarium.. LDX is a useful addition to the formulary, showing similar efficacy and safety profiles to other stimulants.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate

The purpose of this article is to assist pediatric neurologists in practice and in training to better understand and distinguish between several of the most commonly prescribed treatments for attention-deficit/hyperactivity disorder (ADHD) in school-aged children. Among the various pharmacotherapies available for ADHD, 4 specific medications will be reviewed: oral release osmotic system methylphenidate hydrochloride (CON; Concerta, McNeil Pharmaceuticals), lisdexamfetamine dimesylate (LDX; Vyvanse, Shire Pharmaceuticals), atomoxetine (ATX; Strattera, Eli Lilly), and guanfacine extended-release (GXR; Intuniv, Shire Pharmaceuticals). This article contains information including medication-release pattern, administration including available dosing, adverse reactions, and case studies to serve as a guide to help determine when a particular treatment might be more appropriate than another. Although ADHD is apparent across the lifespan, this article will focus on children with ADHD from ages 6 to 12 years old. Importantly, although a number of stimulant and nonstimulant treatment options are available for school-aged children diagnosed with ADHD, choosing the best treatment options is highly dependent on obtaining thorough family and medical histories.

Topics: Adrenergic alpha-2 Receptor Agonists; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Propylamines

Lisdexamfetamine dimesylate (LDX) is a once-daily medication approved by the US Food and Drug Administration for the management of attention-deficit/hyperactivity disorder (ADHD) in children (aged 6-12 years) and adults.. This article reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of LDX.. Studies, abstracts, reviews, and consensus statements published in English were identified through computerized searches of MEDLINE (1966-August 2008) and International Pharmaceutical Abstracts (1977-August 2008) using search headings lisdexamfetamine dimesylate, attention-deficit/hyperactivity disorder, NRP 104, NRP104-201, NRP104-301, NRP104-302, NRP104-303, and stimulant. Selected information provided by the manufacturer of LDX was included, as were all pertinent clinical trials. The reference lists of identified articles were also searched for pertinent information. Relevant abstracts presented at annual professional meetings were included as well.. Several studies have evaluated the pharmacokinetics of LDX in pediatric patients (6-12 years of age) and healthy adults with ADHD. LDX, a prodrug that is therapeutically inactive until metabolized in the body to dextroamphetamine (d-amphetamine), follows linear pharmacokinetics at therapeutic doses (30-70 mg). The efficacy of LDX in the treatment of ADHD was established on the basis of 1 long-term and 2 short-term controlled clinical trials in children who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for ADHD (either the combined or the hyperactive-impulsive subtype) and in 1 clinical trial with adults with ADHD. The efficacy trials in children found significant improvements in scores on the Swanson, Kotkin, Agler, M-Flynn, and Pelham deportment sub-scales, the Permanent Product Measure of Performance (Attempted and Correct), and the ADHD Rating Scale Version IV (ADHD-RS-IV) compared with placebo (all, P < 0.001). In the clinical studies designed to measure duration of effect, LDX, compared with placebo, provided efficacy for a full treatment day, up through and including 6 PM, based on parent ratings (Conners' Parent Rating Scale-Revised Short Form) in the morning, afternoon, and early evening (all, P < 0.001). Data from a long-term, open-label extension study that assessed the safety, tolerability, and efficacy of LDX for up to 12 months found LDX treatment resulted in significant improvement (>60%) from baseline in the ADHD-RS-IV at end point (P < 0.001), with good tolerability. The trial in adults found significant improvements in ADHD-RS scores at end point in patients receiving LDX (30,50, and 70 mg) (P < 0.001 for all active doses); significant improvements in ADHD-RS (using adult prompts) scores were observed at each postbaseline weekly assessment, with improvements noted within the first week in all active treatment arms. Results from human abuse liability studies noted that LDX had lower abuse-related drug-liking scores compared with immediate-release d-amphetamine at equivalent doses. The most common adverse events reported with LDX were typical of amphetamine products and included decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea.. Current evidence supports the efficacy and tolerability of LDX as a treatment option for the management of children (aged 6-12 years) and adults with ADHD. As such, LDX may be an integral part of a total treatment program for ADHD that can include other measures such as psychological, educational, and social interventions.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Substance-Related Disorders

To review the pharmacology, pharmacokinetics, efficacy, and safety of the prodrug lisdexamfetamine for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults and describe its potential place in therapy.. Primary literature published between January 1, 1990, and August 1, 2008, was selected from PubMed using the search key words lisdexamfetamine, Vyvanse, and NRP104. References of selected publications were also reviewed. Posters and abstracts of research presented at national meetings were reviewed when available. The product labeling for Vyvanse was also used.. Preference was given to published, randomized, and controlled research describing the pharmacokinetics, efficacy, and safety of lisdexamfetamine. Noncontrolled studies, postmarketing reports, and poster presentations were considered secondly. All published studies were included.. Lisdexamfetamine is a prodrug of dextroamphetamine covalently bound to l-lysine, which is activated during first-pass metabolism. The unique pharmacokinetic profile owing to lisdexamfetamine's prodrug design and rate-limited enzymatic biotransformation allows for once-daily dosing with a duration of activity of approximately 12 hours. Lisdexamfetamine has been proven to reduce the symptoms of ADHD both in children aged 6-12 years and adults aged 18-55 years, decreasing ADHD rating scale scores by approximately 27 and 19 points, respectively. Adverse effects with an incidence greater than 10% during preclinical trials included appetite suppression, insomnia, and headache. Lisdexamfetamine's unique pharmacokinetic properties may provide additional safety with regard to reducing abuse potential. As with other central nervous system (CNS) stimulants, concerns regarding sudden cardiac death and adverse effects on growth also apply to lisdexamfetamine.. Lisdexamfetamine provides another amphetamine-based CNS stimulant option for treatment of children and adults with ADHD. However, its use may be limited by a lack of significant differentiation when compared with currently used stimulants and a lack of evidence to support its use in adolescents.

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Tachycardia

The pharmacology, pharmacokinetics, indications, clinical efficacy, adverse effects, drug interactions, dosage, and administration of lisdexamfetamine are reviewed.. Lisdexamfetamine is the first prodrug formulation of the stimulant dextroamphetamine. It is approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children age 6-12 years and adults. Due to the need for enzymatic hydrolysis, there is a decreased liability for misuse and diversion with lisdexamfetamine. Moreover, due to the rate-limiting nature of hydrolysis, the toxicity potential and chances of overdose with lisdexamfetamine are reduced. The recommended starting dosage of lisdexamfetamine is 30 mg orally daily, which can be adjusted to a maximum dosage of 70 mg daily. Clinical trials in children age 6-12 years with ADHD found significant reductions in the ADHD symptoms with lisdexamfetamine compared with placebo. However, clinical studies in adolescents have not been conducted. The efficacy and safety of lisdexamfetamine in children with ADHD and comorbid psychiatric disorders also remain to be assessed. A controlled trial in adults similarly showed significant improvements in ADHD symptoms in all treatment groups. Long-term clinical trials and head-to-head comparison trials with existing stimulant formulations are necessary. The most common adverse effects include decreased appetite, insomnia, irritability, dizziness, and weight loss.. Clinical trials in children age 6-12 years and adults with ADHD have shown lisdexamfetamine to be safe and effective, with significant improvement of ADHD-related rating scores. However, the efficacy and safety of lisdexamfetamine in children with ADHD and comorbid psychiatric disorders have not been assessed.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Interactions; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Psychiatric Status Rating Scales

Stimulants are extremely effective and safe and have been the mainstay for the pharmacological treatment of attention deficit hyperactivity disorder (ADHD) for many years. However, there have been some concerns regarding their abuse, especially by teenagers and young adults. Lisdexamfetamine was recently approved for the treatment of ADHD in 6-12-year-olds and provides a novel approach to the treatment of ADHD. Lisdexamfetamine is a prodrug comprised of dextroamphetamine covalently attached to an essential amino acid, L-lysine. Following oral administration, the amide linkage between the two molecules is enzymatically hydrolyzed in the gastrointestinal tract, thus releasing active dextroamphetamine, which mediates the therapeutic effect in a fashion similar to other stimulants. The parent drug does not bind to sites responsible for the reuptake of norepinephrine and dopamine in vitro. Lisdexamfetamine does not produce high dextroamphetamine levels when injected or snorted, and thus may have lower abuse potential compared to conventional stimulants. Lisdexamfetamine appears to have efficacy and tolerability comparable to other extended-release stimulant formulations used to treat ADHD, but reduced potential for abuse-related liking effects. Compared to equivalent amounts of immediate-release dextroamphetamine.

Topics: Attention Deficit Disorder with Hyperactivity; Child; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate

This article reviews the unique prodrug stimulant lisdexamfetamine dimesylate (LDX, Vyvanse), an approved treatment for attention-deficit/hyperactivity disorder. LDX is an inactive prodrug in which l-lysine is chemically bonded to d-amphetamine. Although its efficacy is not significantly different from that of other stimulants, LDX may be different with respect to potential toxicity and abuse liability. In this article, I will review the short-term controlled studies that were the basis for LDX's approval for both children and adults; the lack of and need for more long-term studies; two double-blind, placebo-controlled, crossover studies that examined LDX's abuse liability; and clinical uses for the drug. The clinical implications stemming from LDX's unique characteristics are also discussed.

Topics: Attention Deficit Disorder with Hyperactivity; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Drug Administration Schedule; Humans; Lisdexamfetamine Dimesylate; Nurse's Role; Placebos; Prodrugs; Psychiatric Nursing; Substance-Related Disorders; Treatment Outcome

The names assigned to attention-deficit/hyperactive disorder (ADHD) have changed over the years. ADHD cannot be cured, and the patient with ADHD journeys through life with a burden. Although ADHD is most commonly studied in school-aged children, it is a syndrome that spans the life cycle, through adolescence and into adulthood. Improvements in patient adherence to pharmacologic treatment, attributable to the launch of new formulations, the availability of new non-schedule II drugs, and the development of novel drugs in late-stage clinical trials, are transforming the treatment of ADHD. For example, atomoxetine is a nonstimulant treatment, and lisdexamfetamine was developed with the goal of providing an extended duration of effect with a reduced potential for abuse, overdose toxicity, and drug tampering. Known adverse effects of stimulant treatment of ADHD include appetite suppression and sleep disturbance. Other adverse effects, such as growth suppression and substance use disorder, are controversial. The US Food and Drug Administration (FDA) recently issued a public health advisory for drugs approved for the treatment of ADHD to provide more information for patients about potential risks of ADHD medications. Additional research is needed on approaches for treating ADHD in adolescents transitioning into adulthood, as are studies on the relationships between ADHD and comorbidities such as substance use disorder.

Topics: Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Practice Patterns, Physicians'; Prodrugs; Propylamines; Treatment Outcome

Lisdexamfetamine is an amphetamine prodrug, comprising an l-lysine amino acid covalently bonded to dextroamphetamine (d-amphetamine). Lisdexamfetamine is approved in the US for the treatment of attention-deficit hyperactivity disorder in children aged 6-12 years. Lisdexamfetamine is a therapeutically inactive molecule. After oral ingestion, lisdexamfetamine is hydrolyzed to l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, which is responsible for the activity of the drug. In a well designed pharmacodynamic study in adult stimulant abusers, 50 or 100 mg doses of oral lisdexamfetamine had less likability than d-amphetamine 40 mg, suggesting a reduced abuse potential. Through rate-limited hydrolysis in the body, l-lysine is cleaved, gradually releasing pharmacologically active d-amphetamine. The pharmacokinetics of lisdexamfetamine suggest a reduced potential for abuse. In two well designed trials in children aged 6-12 years with attention-deficit hyperactivity disorder (ADHD), the efficacy of lisdexamfetamine was superior to that of placebo in improving symptoms associated with ADHD. Adverse events with lisdexamfetamine were, in general, mild to moderate in severity and consistent with those commonly reported with amphetamine.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate

Lisdexamfetamine dimesylate (LDX) is the only drug currently approved by the FDA for the treatment of Binge-Eating Disorder (BED), but little is known about the behavioural mechanisms that underpin the efficacy of LDX in treating BED. We examined the behavioural and neural effects of an acute dose of LDX (50 mg) in 22 women with binge-eating symptomatology using a randomised, crossover, double-blind, placebo-controlled experimental medicine design. LDX reduced self-reported appetite ratings and intake of both a pasta meal and a palatable cookie snack. LDX also decreased the eating rate of pasta but not of cookies and reduced self-reported liking ratings for pasta at the end of the meal. When viewing food pictures during an fMRI scan, LDX reduced activity bilaterally in the thalamus. LDX enhanced sustained attention and reduced impulsive responding in a continuous performance task but had no effect on emotional bias or working memory. These results suggest the observed effects of LDX on food intake (and by implication the efficacy of LDX in treating BED) may be related to the actions of the drug to enhance satiety, reduce food-related reward responding when full and/or increase cognitive control. Novel pharmacotherapies for BED might be most effective if they have a broad spectrum of effects on appetite, reward and cognition.

Topics: Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Biomedical Research; Central Nervous System Stimulants; Cognition; Dextroamphetamine; Double-Blind Method; Feeding Behavior; Female; Humans; Lisdexamfetamine Dimesylate; Reward; Treatment Outcome

Psychostimulants are frequently used to treat attention-deficit/hyperactivity disorder (ADHD), but side effects are common leading to many patients discontinuing treatment. Identifying neural mechanisms by which psychostimulants attenuate symptoms may guide the development of more refined and tolerable therapeutics.. We conducted a 12-week, randomized, placebo-controlled trial (RCT) of a long-acting amphetamine, lisdexamfetamine (LDEX), in patients with ADHD, ages 6-25 years old. Of the 58 participants who participated in the RCT, 49 completed pre- and post-RCT magnetic resonance imaging scanning with adequate data quality. Healthy controls (HCs; n = 46) were included for comparison. Treatment effects on striatal and thalamic functional connectivity (FC) were identified using static (time-averaged) and dynamic (time-varying) measures and then correlated with symptom improvement. Analyses were repeated in independent samples from the Adolescent Brain Cognitive Development study (n = 103) and the ADHD-200 Consortium (n = 213).. In 49 participants (25 LDEX; 24 Placebo), LDEX increased static and decreased dynamic FC (DFC). However, only DFC was associated with the therapeutic effects of LDEX. Additionally, at baseline, DFC was elevated in unmedicated-ADHD participants relative to HCs. Independent samples yielded similar findings - ADHD was associated with increased DFC, and psychostimulants with reduced DFC. Static FC findings were inconsistent across samples.. Changes in dynamic, but not static, FC were associated with the therapeutic effects of psychostimulants. While prior research has focused on static FC, DFC may offer a more reliable target for new ADHD interventions aimed at stabilizing network dynamics, though this needs confirmation with subsequent investigations.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Brain; Brain Mapping; Central Nervous System Stimulants; Child; Humans; Lisdexamfetamine Dimesylate; Magnetic Resonance Imaging; Young Adult

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).. 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).. 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).. 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.. Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-Deficit/Hyperactivity Disorder; http://www.. gov; NCT03260205.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

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.. 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).. 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.

Topics: Alcoholism; Amphetamine-Related Disorders; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methamphetamine; Pilot Projects; Substance Withdrawal Syndrome; Treatment Outcome

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome; Young Adult

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognition Disorders; Cross-Over Studies; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales

As an extension of a phase 2/3 study evaluating the efficacy and safety of lisdexamfetamine dimesylate (LDX) 30, 50, or 70 mg/d for 4 weeks in Japanese patients aged 6-17 years with attention-deficit/hyperactivity disorder (ADHD), this study evaluated its long-term safety and efficacy.. This was a multicenter, open-label study of LDX for 53 weeks. Safety was assessed by regular medical examination for treatment-emergent adverse events (TEAEs); regular recording of body weight, vital signs, and laboratory test values; and completion of dependence questionnaires. Efficacy was assessed using Japanese versions of the ADHD-Rating Scale-IV (ADHD-RS-IV) and Conners' 3rd edition Parent Rating Scale (Conners 3); plus Clinical Global Impression-Improvement (CGI-I), Clinical Global Impression-Severity, and Parent Global Assessment (PGA) scales.. Of 132 enrolled patients, 104 completed the trial. Most frequent treatment-related TEAEs were decreased appetite (73.5%), initial insomnia (39.4%), and weight decrease (22.0%). Most TEAEs were mild (82.6% of patients). There were no serious or severe TEAEs or deaths. No treatment-related TEAEs were associated with blood pressure or pulse rate, and no patient had a QTcF interval >500 ms. Statistically significant improvement from baseline to week 53 was observed in the mean ADHD-Rating Scale-IV total score and mean Conners 3 subscale scores. Most patients showed improvement on the CGI-I (78%) and PGA (76.5%) scales.. No significant safety issues were observed with LDX 30, 50, or 70 mg/d administered for 1 year in Japanese children and adolescents with ADHD. LDX was associated with long-term reductions in ADHD symptoms and severity.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Japan; Lisdexamfetamine Dimesylate; Longitudinal Studies; Outcome Assessment, Health Care

Executive function (EF) deficits are not generally considered synonymous with attention-deficit/hyperactivity disorder (ADHD). Evidence suggests stimulants improve ADHD symptoms and EF deficits in adults with ADHD, but the relationships between improvements in these domains have not been studied.. These post hoc analyses used data from a 10-week double-blind, placebo-controlled study of adults with ADHD and EF deficits treated with lisdexamfetamine dimesylate (30-70 mg) or placebo conducted from May 2010 to November 2010. Efficacy endpoints included change from baseline at week 10/early termination (ET) in self-report Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) Global Executive Composite (GEC) T-score and ADHD-Rating Scale with Adult Prompts total score (ADHD-RS-AP-TS). Relationships between ADHD symptom and EF changes were examined using recursive path analyses.. Mediation proportions were 0.62 (indirect and total treatment effect coefficients [95% CI]: -6.85 [-9.83 to -3.86] and -11.12 [-14.88 to -7.37]) for self-report BRIEF-A GEC T-score change from baseline at week 10/ET on ADHD-RS-AP-TS change from baseline at week 10/ET and 0.93 (indirect and total treatment effect coefficients [95% CI]: -10.34 [-14.11 to -6.57] and -11.18 [-15.80 to -6.55]) for ADHD-RS-AP-TS change from baseline at week 10/ET on self-report BRIEF-A GEC T-score change from baseline at week 10/ET.. Although these data suggest ADHD symptom and EF deficit improvement following lisdexamfetamine are interdependent, it is advantageous to use measures like the BRIEF-A to assess stimulant effects on the wide range of EF deficits associated with ADHD that are not captured by the ADHD-RS-AP alone.. Data used in this secondary analysis came from ClinicalTrials.gov identifier: NCT01101022.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Cognitive Dysfunction; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Neuropsychological Tests; Outcome Assessment, Health Care; Young Adult

Attention-deficit/hyperactivity disorder (ADHD) is present in 25%-50% of parents of children with ADHD, compromising parenting and child behavioral treatment. Efforts to treat multiplex ADHD families have not compared behavioral parenting interventions to parent psychopharmacology without confounds of other treatments. This report describes a pilot early intervention study directly comparing parent lisdexamfetamine dimesylate (LDX) to behavioral parent training (BPT) in families in which the mother had currently untreated ADHD and the young child displayed ADHD symptoms.. Mothers with ADHD (N = 35) of 4- to 8-year-old stimulant-naive children (N = 35) were randomly assigned to an 8-week trial of LDX (starting at 20 mg/d and titrated to a maximum of 70 mg/d) or BPT. Outcomes included multi-method, multi-informant measures of (1) maternal ADHD symptoms (Conners' Adult ADHD Rating Scales) and impairment (Clinical Global Impressions-Severity of Illness scale [CGI-S] and CGI-Improvement scale [CGI-I]), (2) parenting (Alabama Parenting Questionnaire [APQ] and Dyadic Parent-Child Interaction Coding System, Fourth Edition), and (3) child ADHD symptoms (Conners Parent Rating Scale Revised-Short Form and Conners Early Childhood Scale) and impairment (CGI-S, CGI-I, and Child Impairment Rating Scale).. At 8 weeks, both treatments improved mothers' self-reported emotion regulation and mothers' functioning on the CGI, but only LDX improved mothers' self-reported core ADHD symptoms. LDX was associated with improvement in parents' perception of their own ADHD symptoms (Conners Inattention [P < .0001] and ADHD Index scores [P < .0001]) and their child's ADHD symptoms (P = .009). Fifty-six percent of the mothers treated with LDX (n = 10) were "much" or "very much" improved with regard to their adult ADHD based on the CGI-I scores versus 6% of mothers receiving BPT (n = 1; P = .003). BPT improved parenting on self-reported positive parenting (P = .007), inconsistent discipline (P > .0001), and corporal punishment (P = .001), while LDX improved reported inconsistent discipline (P = .001) and corporal punishment (P = .04) on the APQ, consistent with prior research. In contrast to parental LDX, which did not improve observed parenting, BPT was associated with increased positive parenting during child-directed play (P = .0002) and clean-up (P = .04) and less negative parenting (P = .04) during child-directed play. Six percent of children (n = 1) whose mothers were randomized to LDX (n = 18) were "much" or "very much" improved on the CGI-I compared to 35% (n = 16) of those treated with BPT (P = .04).. LDX and BPT each had unique effects on maternal ADHD symptoms and parenting, but modest effects on at-risk children. In general, LDX was more effective at treating mothers' core ADHD symptoms, but both LDX and BPT improved mothers' emotion regulation, and BPT resulted in more consistent effects on parenting measures via both maternal report and direct observation. As most children remained significantly impaired after 8 weeks of unimodal treatment, combination treatment and/or longer treatment duration may be necessary to improve functioning of multiplex ADHD families.. ClinicalTrials.gov identifier: NCT01816074​.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Behavior Therapy; Central Nervous System Stimulants; Child; Child, Preschool; Female; Humans; Lisdexamfetamine Dimesylate; Mothers; Parenting; Psychiatric Status Rating Scales; Treatment Outcome

SPD489-404 was the first 2-year safety study of lisdexamfetamine dimesylate in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. In accordance with advice from the European Medicines Agency, assessment of cognitive function was a predefined safety outcome in SPD489-404.. The objective of this study was to assess cognitive function over 2 years in study SPD489-404, using the Cambridge Neuropsychological Test Automated Battery (CANTAB).. Participants aged 6-17 years received dose-optimised open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) for 104 weeks. Cognition was assessed using four CANTAB tasks; Delayed Matching to Sample (DMS), Spatial Working Memory (SWM), Stop Signal Task (SST) and Reaction Time (RTI). Key and additional variables were pre-specified for each CANTAB task; groupwise mean percentage changes in key variables from baseline of > 5% were considered potentially clinically significant.. All 314 enrolled participants received lisdexamfetamine dimesylate and were included in the safety population, and 191 (60.8%) completed the study. No potentially clinically significant deteriorations from baseline were observed in any key CANTAB variable over the 2 years of the study. Based on predefined thresholds, potentially clinically significant improvements from baseline were observed at 6 months (DMS median reaction time, mean per cent change, - 6.6%; SWM total between-search errors, - 22.8%; SST stop signal reaction time, -18.9%), and at the last on-treatment assessment (DMS median reaction time, - 6.5%; SWM total between-search errors, - 32.6%; SST stop signal reaction time, - 25.7%).. Lisdexamfetamine dimesylate treatment for 2 years was not associated with deterioration of cognitive function in children and adolescents with attention-deficit/hyperactivity disorder. Although improvements in some cognitive measures were observed, lack of a control group makes interpretation of the findings difficult. Further studies of the impact of stimulants on cognition are required. CLINICALTRIALS.. NCT01328756.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cognition; Dose-Response Relationship, Drug; Female; Humans; Lisdexamfetamine Dimesylate; Male; Neuropsychological Tests; Treatment Outcome

Prefrontal-limbic circuits that form the neural architecture for emotion to influence behavior have been implicated in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and represent a potentially important target of medication treatment that has not been substantively evaluated. This study tested the effect of the psychostimulant prodrug lisdexamfetamine dimesylate on amygdala activation and connectivity during the emotional bias of response execution and inhibition.. Twenty-five adults with ADHD were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task after 3 to 4 weeks of lisdexamfetamine treatment and 3 weeks off medication in a randomized, counterbalanced, hybrid crossover design. Drug, trial type, and face emotion (happy, sad, or neutral) were included as within-subjects factors in repeated measures analyses of activation and connectivity.. Lisdexamfetamine was associated with increased right amygdala activation and reduced psychophysiological interactions with the orbital aspect of the left inferior frontal gyrus specifically for responses to sad faces compared with placebo, but there was no effect on the accuracy of response execution or inhibition. The relative gain in right amygdala activation in response to sad faces for lisdexamfetamine was correlated with a reduction in symptoms of ADHD.. Treatment with lisdexamfetamine potentiates affective encoding in amygdala, purportedly via catecholaminergic mechanisms, but functionally disconnects the amygdala from inferior frontal regions that encode behavioral significance-resulting in reduced emotional bias of cognitive control. Pinpointing the neurophysiologic underpinnings of therapeutic improvement with lisdexamfetamine represents a first step in developing targeted approaches to treatment of ADHD.

Topics: Adult; Amygdala; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Emotions; Executive Function; Facial Expression; Female; Functional Neuroimaging; Humans; Inhibition, Psychological; Lisdexamfetamine Dimesylate; Magnetic Resonance Imaging; Male; Middle Aged; Prefrontal Cortex; Young Adult

Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents.. The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder.. Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging.. The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m. Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS.. NCT01328756.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Body Mass Index; Body Size; Central Nervous System Stimulants; Child; Female; Humans; Lisdexamfetamine Dimesylate; Male; Puberty; Treatment Outcome

Attention-deficit/hyperactivity disorder (ADHD) is increasingly recognized as a persistent disorder requiring long-term management.. Our objective was to evaluate the 2-year safety and efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with ADHD.. Participants (aged 6-17 years) with ADHD received open-label, dose-optimized LDX 30, 50, or 70 mg/day for 104 weeks. Safety monitoring included treatment-emergent adverse events (TEAEs), vital signs, electrocardiography, and growth. The TEAEs decreased appetite, weight decrease, insomnia events (including insomnia, initial insomnia, middle insomnia, and terminal insomnia), headache, and psychiatric TEAEs were pre-defined as being of special interest. Efficacy was assessed as a secondary objective using the ADHD Rating Scale IV (ADHD-RS-IV), the Clinical Global Impressions-Improvement (CGI-I) scale, and the CGI-Severity (CGI-S) scale.. The safety profile of LDX in this longer-term study was similar to that reported in previous studies. The efficacy of LDX was maintained throughout the 2-year study period. CLINICALTRIALS.. NCT01328756.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Body Weight; Central Nervous System Stimulants; Child; Electrocardiography; Europe; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome

To describe symptom rebound in children with ADHD treated with lisdexamfetamine dimesylate (LDX) or placebo.. During a 4-week, randomized, double-blind, placebo-controlled trial of LDX, parents/caregivers completed the Conners' Parent Rating Scale-Revised: Short Form symptom rating scale throughout the day. Response, rebound, and emotional lability (EL) were assessed post hoc based on predefined criteria.. Most participants given LDX ( n = 207) were responders throughout the day (50.7%-55.6%) versus placebo ( n = 72; 11.1%-22.2%). A total of seven (3.4%) LDX participants showed rebound in the afternoon and/or evening versus seven (9.7%) with placebo. In both groups, most incidences of rebound occurred in the evening. EL (mean) was higher in LDX rebounders and nonresponders (range = 4.2-9.0) versus LDX responders (range = 1.3-1.6) and versus placebo rebounders (range = 0.7-1.9).. ADHD symptom rebound occurred in few participants (3.3%) given LDX (accompanied by clinically significant EL). Overall, more participants given LDX versus placebo responded throughout the day.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Double-Blind Method; Drug Administration Schedule; Emotions; Female; Humans; Lisdexamfetamine Dimesylate; Male; Mood Disorders; Parents; Treatment Outcome

(a) Evaluate the efficacy and duration of effect of lisdexamfetamine dimesylate (LDX) in adult ADHD. (b) Assess the reliability and validity of the Adult ADHD Medication Smoothness of Effect Scale (AMSES) and Adult ADHD Medication Rebound Scale (AMRS).. Adults ( N = 40) with ADHD were treated with LDX for up to 12 weeks. The primary efficacy measure was the ADHD Rating Scale (ADHD-RS). The psychometric properties of the AMSES and AMRS are analyzed and compared with the ADHD-RS, ADHD Self-Report Scale (ASRS) v1.1 Symptom Checklist, and Time-Sensitive ADHD Symptom Scale (TASS).. ADHD-RS scores were significantly improved with LDX. The AMSES and AMRS had high internal consistency and were correlated with the ADHD-RS, ASRS v1.1 Symptom Checklist, and TASS.. LDX is effective in treating adult ADHD and has a smooth drug effect throughout the day with limited symptom rebound. The AMSES and AMRS are valid and reliable measures.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Drug Administration Schedule; Female; Humans; Lisdexamfetamine Dimesylate; Male; Medication Adherence; Middle Aged; Psychometrics; Reproducibility of Results; Self Report; Treatment Outcome; Young Adult

To examine the level of agreement between self- and observer-reported ratings of ADHD symptoms and executive function (EF) behaviors in adults with moderate to severe ADHD and EF deficits.. During a 10-week, randomized, double-blind, placebo-controlled study, the effect of lisdexamfetamine dimesylate (LDX) on EF was assessed by self-report and informant report (Behavior Rating Inventory of Executive Function-Adult Version), and ADHD symptoms were assessed by clinician- and informant-rated scales (ADHD Rating Scale IV with adult prompts and Conners' Adult ADHD Rating Scales-Observer Report: Short Version, respectively). Post hoc analysis used Pearson correlations to assess relationships between self- and informant-rated EF and clinician- and informant-rated ADHD symptoms.. Correlations between self-ratings versus informant ratings and clinician versus informant ratings were greater at Week 10/early termination (EF: placebo [0.5231-0.6085], LDX [0.3543-0.5167]; ADHD symptoms: placebo [0.4169], LDX [0.4004]) versus baseline (EF: placebo [0.3208-0.5023], LDX [0.2852-0.3439]; ADHD symptoms: placebo [0.1511], LDX [-0.0408]).. LDX improved EF and ADHD symptoms, based on participant, informant, and clinician ratings. Increased rater agreement over time may reflect improved symptom awareness.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Awareness; Central Nervous System Stimulants; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Self Report; Treatment Outcome; Young Adult

Lisdexamfetamine (LDX) is a prodrug and consists of an active moiety, d-amphetamine, bound to lysine. Clinically, d-amphetamine becomes available postcleavage of the prodrug in the blood stream. Clinical effects of LDX in attention-deficit/hyperactivity disorder (ADHD) have been shown to persist up to 14 hours; however, pharmacokinetic (PK) data of LDX and amphetamine in ADHD adults are not currently available.. (1) To examine PK data of LDX and d-amphetamine in plasma and (2) to compare such PK data with Time-Sensitive ADHD Symptom Scale (TASS) ratings (PK vs. pharmacodynamic [PD]).. Plasma d-amphetamine/LDX levels and TASS ratings were obtained immediately before morning dosing and then 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdosing in 21 adults with ADHD treated with 5 weeks of single-blind LDX up to 70 mg/day (after 1 week single-blind placebo). ADHD Rating Scale scores were obtained at the beginning of the visit, before morning dosing.. LDX levels peaked at 1.5 hours after administration (T. (1) Prodrug LDX levels peaked fairly rapidly and declined, while d-amphetamine levels peaked 3 hours later than LDX levels and persisted throughout the day and (2) the absence of PK/PD correlations between PK data and TASS ratings may be due to the subjects being tested in a controlled nonattention demanding environment.

Topics: Adult; Area Under Curve; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Prodrugs; Psychiatric Status Rating Scales; Single-Blind Method; Time Factors; Treatment Outcome; Young Adult

This study examines the effects of parental stimulant medication treatment on parent ratings of parent-child functioning. Ratings of parent-child functioning in the home setting and immediately following a laboratory-based parent-child interaction were collected.. Participants were 20 parents who along with their children (ages 5-12 years) were diagnosed with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) attention-deficit/hyperactivity disorder (ADHD). Parents completed an open-label titration to determine their optimal dose of lisdexamfetamine (30, 50, or 70 mg/day) and then completed a month-long double-blind randomized pharmacological intervention for parental ADHD. Effects of parental stimulant medication administered for an extended duration were assessed by parent ratings of parent-child functioning in the home setting and immediately following a laboratory parent-child interaction task conducted at an academic mental health center. Data were collected from September 2010 to June 2013.. Stimulant medication versus placebo was associated with larger reductions in parental ADHD (d = 1.01-1.09), impairment (d = 0.67-0.82), and executive dysfunction (d = 0.74-0.94) in the home setting. No significant benefits of stimulant medication emerged in measures of parenting or child behavior at home. In the laboratory setting, parents treated with stimulant medication versus placebo reported fewer ADHD symptoms (d = 1.01-1.05) and their interaction was more successful (d = 0.83) and pleasant (d = 0.92). Several additional trends emerged showing beneficial effects of stimulant medication on parent-child functioning.. Parents treated with stimulant medication evidenced some improvements in parent-child functioning, which support the use of pharmacological intervention to improve functioning in families with parent-child ADHD.. NCT01127607.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Executive Function; Female; Humans; Interpersonal Relations; Lisdexamfetamine Dimesylate; Male; Parent-Child Relations; Parenting; Parents; Psychiatric Status Rating Scales; Surveys and Questionnaires

Attention-deficit/hyperactivity disorder (ADHD) is associated with functional impairments in multiple domains of patients' lives. A secondary objective of this randomized, active-controlled, head-to-head, double-blind, dose-optimized clinical trial was to compare the effects of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) on functional impairment in children and adolescents with ADHD. Patients aged 6-17 years with an ADHD Rating Scale IV total score ≥ 28 and an inadequate response to methylphenidate treatment (judged by investigators) were randomized (1:1) to once-daily LDX or ATX for 9 weeks. Parents/guardians completed the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) at baseline and at week 9 or early termination. p values were nominal and not corrected for multiple comparisons. Of 267 randomized patients, 200 completed the study (LDX 99, ATX 101). At baseline, mean WFIRS-P total score in the LDX group was 0.95 [standard deviation (SD) 0.474; 95% confidence interval (CI) 0.87, 1.03] and in the ATX group was 0.91 (0.513; 0.82, 1.00). Scores in all WFIRS-P domains improved from baseline to endpoint in both groups, with least-squares mean changes in total score of -0.35 (95% CI -0.42, -0.29) for LDX and -0.27 (-0.33, -0.20) for ATX. The difference between LDX and ATX was statistically significant (p < 0.05) for the Learning and School (effect size of LDX vs ATX, 0.43) and Social Activities (0.34) domains and for total score (0.27). Both treatments reduced functional impairment in children and adolescents with ADHD; LDX was statistically significantly more effective than ATX in two of six domains and in total score.

Topics: Adolescent; Atomoxetine Hydrochloride; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Treatment Outcome

The retrospective comparison of test and reference treatment arms in a randomized prospective clinical trial is potentially useful in economic modeling seeking to assess the cost effectiveness of alternative therapies.. To enhance the credibility of such retrospective comparisons, we propose the application of the following adjustments to significance levels obtained from standard statistical methodology: (1) a significance test for the lower bound of the 95 % confidence interval for the observed difference, (2) a conservative Bonferroni method of adjustment for multiple comparisons, (3) an adjusted p-value calculated using Scheffe's single-step method, and (4) Bayesian 95 % credibility intervals with a prior centered at zero.. These adjustments were applied to data from a randomized double-blind concurrent trial (SPD489-325) that established the efficacy and safety of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). Prospectively planned analyses demonstrated that the reduction in the symptoms of ADHD was significantly greater than placebo in patients treated with either LDX or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Retrospective analyses showed that the improvement in the symptoms of ADHD was greater in patients treated with LDX than OROS-MPH. We now show that this observation remained significant after the application of the four statistical penalties.. By adjusting the significance level, it is possible to compare quantitatively such retrospective results with prospectively defined comparisons. However, the qualitative level of such retrospective evidence should remain secondary to that obtained from prospectively specified comparisons in a randomized clinical trial.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Bayes Theorem; Child; Dextroamphetamine; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Retrospective Studies

Lisdexamfetamine dimesylate (LDX) is a long-acting, prodrug stimulant therapy for patients with attention-deficit/hyperactivity disorder (ADHD). This randomized placebo-controlled trial of an optimized daily dose of LDX (30, 50 or 70 mg) was conducted in children and adolescents (aged 6-17 years) with ADHD. To evaluate the efficacy of LDX throughout the day, symptoms and behaviors of ADHD were evaluated using an abbreviated version of the Conners' Parent Rating Scale-Revised (CPRS-R) at 1000, 1400 and 1800 hours following early morning dosing (0700 hours). Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference treatment, but the study was not designed to support a statistical comparison between LDX and OROS-MPH. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107). At baseline, CPRS-R total scores were similar across treatment groups. At endpoint, differences (active treatment - placebo) in least squares (LS) mean change from baseline CPRS-R total scores were statistically significant (P < 0.001) throughout the day for LDX (effect sizes: 1000 hours, 1.42; 1400 hours, 1.41; 1800 hours, 1.30) and OROS-MPH (effect sizes: 1000 hours, 1.04; 1400 hours, 0.98; 1800 hours, 0.92). Differences in LS mean change from baseline to endpoint were statistically significant (P < 0.001) for both active treatments in all four subscales of the CPRS-R (ADHD index, oppositional, hyperactivity and cognitive). In conclusion, improvements relative to placebo in ADHD-related symptoms and behaviors in children and adolescents receiving a single morning dose of LDX or OROS-MPH were maintained throughout the day and were ongoing at the last measurement in the evening (1800 hours).

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Parents; Prodrugs; Treatment Outcome

Understanding the nature and time course of the pharmacodynamic effects of attention-deficit/hyperactivity disorder (ADHD) medications is useful. The Cognitive Drug Research Computerized Battery of Tests (CDR-CBT) is a 20-min battery of ten standardized, validated neuropsychometric tasks.. This pilot study examined the sensitivity and responsiveness of the CDR-CBT for assessing cognitive function in adults with ADHD prior to and up to 16 h postdose during treatment with lisdexamfetamine dimesylate (LDX) or mixed amphetamine salts immediate release (MAS-IR; various generics available).. This was a double-blind three-period crossover study. Participants received LDX 50 mg/day, MAS-IR 20 mg/day, and placebo (~7 a.m.) for 7 days each in randomized order. CDR-CBT was administered on day 1 of period 1 and day 7 of each period at scheduled times between -0.5 (predose) and 16 h postdose. Composite power of attention (PoA) score (sum of simple reaction time, choice reaction time, and digit vigilance speed) was the primary outcome measure. The Conners' Adult ADHD Rating Scales-Self-Report: Short Version (CAARS-S:S) was administered at baseline and on day 1 of period 1, and days 6 and 7 of each treatment period. Tertiary outcomes included CDR-CBT composite continuity of attention scores, its component task scores, cognitive reaction time, and response variability scores. No inferential statistical comparisons were conducted. Safety assessments included adverse events (AEs) and vital signs.. This analysis included 18 participants (mean age 30.8 years); one withdrew because of AEs. Mean pretreatment PoA scores were 1175.9-1361.2 ms, scores commensurate with a normative age of >40 years. Maximum reductions in PoA scores with LDX and MAS-IR occurred at 5 h postdose at day 7 (least squares mean difference [95% CI] of -150.0 [-235.41 to -64.50] and -79.8 [-165.72 to 6.21] ms vs. placebo, respectively). CAARS-S:S scores were unchanged with LDX and MAS-IR (vs. placebo) at all postdose timepoints. Tertiary attention-related CDR-CBT outcomes were sensitive to LDX and MAS-IR (vs. placebo). Treatment-emergent AEs and vital signs were consistent with previous studies in adult ADHD.. In adults with ADHD, PoA scores indicated impaired attention at baseline and response to treatment with LDX and MAS-IR (vs. placebo), demonstrating value for measuring the time course of pharmacologic treatment effects.

Topics: Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cognition; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Neuropsychological Tests; Pilot Projects; Psychometrics; Reaction Time; Sensitivity and Specificity; Time Factors; Treatment Outcome; Young Adult

This study examines the effects of parental lisdexamfetamine (LDX) treatment on parent-child interactions.. Participants were 30 parents (27% were male) and their children aged 5-12 years, both diagnosed with DSM-IV attention-deficit/hyperactivity disorder (ADHD). Optimal LDX dose (30, 50, or 70 mg/day) was determined for parents during a 3-week open-label titration, followed by a within-subjects trial of the acute impact of LDX and placebo on observable parent-child interactions. Two laboratory-based, parent-child interactions simulating typical family tasks (e.g., homework, joint play) were conducted within 2 weeks, once with the adult on a blinded optimal dose of LDX and once on placebo (phase I). Parents were then randomly assigned to continue blinded treatment with LDX or placebo for another month followed by a third interaction task (phase II) to assess the ongoing effects of LDX on parent-child interactions. The primary outcome was the change in rate of parenting behaviors coded during the parent-child interaction tasks. Secondary outcomes included observed rates of children's inappropriate behaviors during the laboratory tasks and changes in parental ADHD symptom severity (ADHD-Rating Scale).. Twenty parents (67%) completed the trial. In phase I, medication was associated with a significant reduction in negative talk by parents (p = 0.0066, d = -0.47). There was a Medication × Task interaction (p = 0.0235) with a reduction in children's negative behaviors in the homework phase only (p = 0.0154, d = -0.58). In phase II, LDX was associated with significant increases in praise by parents (d = 0.81) and reductions in parental commands (d = -0.88) and children's inappropriate behaviors (d = -0.84) (all p-values < 0.05). While not reaching statistical significance, LDX was also associated with large reductions in parental verbalizations (d = -0.82), moderate increases in parental responsiveness (d = 0.55), and large reductions in the ratio of commands to verbalizations during the non-homework task (d = -1.05) (all p-values < 0.10). Significant reductions in parental ADHD symptoms vs. placebo were observed (p < 0.005). Loss of appetite, dry mouth, headaches, and delayed sleep onset were the most common adverse events.. Improvements in parent-child interactions emerged over time with LDX treatment of parental ADHD. Results suggest that pharmacological treatment of parental ADHD may improve outcomes in parents and their children.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Parent-Child Relations; Parenting; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

The purpose of this study was to assess long-term improvement in quality of life (QOL) in adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with lisdexamfetamine dimesylate (LDX).. Adolescents with ADHD treated for ≥3 weeks in a 4 week, placebo-controlled study entered a 1 year, open-label study. After the 4 week dose optimization (30, 50, and 70 mg/day LDX) period, treatment was maintained for 48 additional weeks. Change from baseline (of prior study) to week 52/early termination (ET) (of open-label study) in ADHD Rating Scale IV (ADHD-RS-IV) assessed effectiveness, and the Youth QOL-Research Version (YQOL-R) assessed participant-perceived QOL. Post-hoc analyses described effectiveness and QOL for participants with self-perceived poor QOL at baseline (≥1 SD below the mean) versus all others, and for study completers versus study noncompleters.. These post-hoc analyses included 265 participants. Participants with baseline self-perceived poor QOL (n=32) versus all others (n=232) exhibited robust YQOL-R perceptual score changes (improvement) with LDX, emerging by week 28 and maintained to week 52/ET. Week 52/ET mean change score ranged from +9.8 to +17.6 for participants with baseline self-perceived poor QOL and +0.4 to +5.1 for all others; week 52/ET improvements in ADHD-RS-IV total scores were similar, regardless of baseline YQOL-R total score. At week 52/ET, study completers had greater YQOL-R improvements than did noncompleters; ADHD-RS-IV total score changes were also numerically larger at week 52/ET for completers than for noncompleters.. Participant-perceived QOL and ADHD symptoms improved from baseline with LDX in adolescents with ADHD; greatest improvements occurred among participants with baseline self-perceived poor QOL.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Psychiatric Status Rating Scales; Quality of Life; Treatment Outcome

In this phase 3 extension study, the long-term maintenance of efficacy of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) was evaluated using a randomized-withdrawal study design.. European and US patients (6-17 years; N = 276) with ADHD were entered into a 26-week open-label trial of LDX treatment. Those who completed the open-label period (n = 157) were randomized 1:1 to their optimized dose of LDX (30, 50, or 70 mg per day) or placebo for a 6-week randomized-withdrawal period (RWP). The primary efficacy measure was the proportion of patients meeting treatment failure criteria (≥50% increase in ADHD Rating Scale IV total score and ≥2-point increase in Clinical Global Impressions-Severity of Illness [CGI-S] score, compared with RWP start point). Safety and tolerability were also evaluated.. During the RWP (LDX, n = 78; placebo, n = 79), significantly fewer patients receiving LDX met treatment failure criteria (15.8%) compared with those receiving placebo (67.5%; difference = -51.7%; 95% confidence interval = -65.0, -38.5; p < .001 ). Most treatment failures occurred at or before the week 2 visit after randomization. Treatment-emergent adverse events were reported in 39.7% and 25.3% of patients receiving LDX and placebo, respectively, during the RWP.. These data demonstrate the maintenance of efficacy of LDX during long-term treatment in children and adolescents with ADHD. The rapid return of symptoms on LDX withdrawal demonstrates the need for continuing treatment. The safety profile of LDX was consistent with that of other stimulants. Clinical trial registration information-Double-Blind, Placebo-Controlled, Randomized Withdrawal, Extension, Safety and Efficacy Study of LDX in Children and Adolescents Aged 6-17; http://clinicaltrials.gov; NCT00784654.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Treatment Failure; Treatment Outcome; Withholding Treatment

Attention deficits are often among the most persistent and debilitating impairments resulting from traumatic brain injury (TBI). This study examined the effects of lisdexamfetamine dimesylate (Vyvanse) in treating attention deficits due to moderate-to-severe TBI. It was the first study of lisdexamfetamine dimesylate with this population and, in fact, was the first controlled trial in this area examining a stimulant medication option other than methylphenidate.. This was a 12-week, randomized, double-blind, placebo-controlled, cross-over trial. A total of 22 rigorously selected cases were enrolled, 13 of whom completed the trial. They were 16-42 years of age and had newly acquired attention deficits persisting for 6-34 months post-injury. They were assessed on a broad range of neuropsychological and behavioural measures at baseline, 6-weeks and at 12-weeks.. Positive treatment effects were found involving selective measures of sustained attention, working memory, response speed stability and endurance and in aspects of executive functioning. No major problems with safety or tolerability were observed. Some moderating treatment effects were found from a broad range of pre-treatment subject characteristics and injury variables examined. Avenues for further research and treatment applications in this area are discussed.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Brain Injuries; Central Nervous System Stimulants; Cross-Over Studies; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Neuropsychological Tests; Treatment Outcome

A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and atomoxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactivity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously.. In this 9-week, double-blind, active-controlled study, patients aged 6-17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients <70 kg: 0.5-1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients ≥70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (≥25, ≥30 or ≥50 %) or a Clinical Global Impressions (CGI)-Improvement (CGI-I) score of 1 or 2 throughout weeks 4-9. CGI-Severity (CGI-S) scores were also assessed, as an indicator of remission.. A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p < 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also significantly (p < 0.05) higher among LDX-treated patients (ADHD-RS-IV ≥25, 66.1 %; ADHD-RS-IV ≥30, 61.4 %; ADHD-RS-IV ≥50, 41.7 %; CGI-I, 52.0 %) than among ATX-treated individuals (ADHD-RS-IV ≥25, 51.1 %; ADHD-RS-IV ≥30, 47.4 %; ADHD-RS-IV ≥50, 23.7 %; CGI-I, 39.3 %). Finally, by week 9, 60.7 % of patients receiving LDX and 46.3 % of those receiving ATX had a CGI-S score of 1 (normal, not at all ill) or 2 (borderline mentally ill), and greater proportions of patients in the LDX group than the ATX group experienced a reduction from baseline of at least one CGI-S category.. Both LDX and ATX treatment were associated with high levels of treatment response in children and adolescents with ADHD and a previous inadequate response to MPH. However, within the parameters of the study, LDX was associated with significantly higher treatment response rates than ATX across all response criteria examined. In addition, higher proportions of patients in the LDX group than the ATX group had a CGI-S score of 1 or 2 by week 9, indicating remission of symptoms. Both treatments were generally well tolerated, with safety profiles consistent with those observed in previous studies.

Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Double-Blind Method; Drug Administration Schedule; Humans; Lisdexamfetamine Dimesylate; Propylamines; Remission Induction; Severity of Illness Index; Treatment Outcome

The stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well tolerated treatment for the symptoms of attention-deficit/hyperactivity disorder (ADHD). Positive impacts of LDX on health-related quality of life and functional impairment have previously been demonstrated in a 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in Europe. Maintenance of these broad benefits, as well as symptomatic control, is a key goal of long-term management of ADHD.. Secondary objectives of this multinational study in children and adolescents with ADHD were to assess the long-term maintenance of effectiveness of LDX in improving health-related quality of life and reducing functional impairment, as gauged using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE: PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.. Patients aged 6-17 years with diagnosed ADHD and a baseline ADHD Rating Scale IV total score of at least 28 were enrolled from the previous European study and from US sites. Patients who completed an open-label LDX treatment period of at least 26 weeks were randomized (1:1) to continue on their optimized dose of LDX or to switch to placebo for a 6-week, double-blind, withdrawal period. Parents completed CHIP-CE: PRF and WFIRS-P questionnaires at weeks 0, 8 and 26 of the open-label period and at weeks 0 and 6 of the randomized-withdrawal period, or at early termination. The endpoint of each period was defined as the last visit with valid data. Effect sizes were the difference (LDX minus placebo) in least-squares (LS)-mean change from baseline to endpoint divided by root-mean-square error. P values were nominal and not adjusted for multiple comparisons.. The open-label and randomized full analysis sets comprised 262 and 153 (LDX n = 76; placebo n = 77) patients, respectively. Mean pretreatment CHIP-CE: PRF T-scores were more than one standard deviation below the normative mean in four of the five domains, and there was significant improvement across all domains from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean CHIP-CE: PRF T-scores deteriorated in all domains in the placebo group, but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Risk Avoidance (effect size 0.829; p < 0.001), Achievement (0.696; p < 0.001) and Satisfaction (0.636; p < 0.001) domains. Mean pretreatment WFIRS-P scores were lowest in the Family domain and the Learning and School domain. WFIRS-P total score and scores in all domains improved significantly from baseline to endpoint of the open-label period. In the randomized-withdrawal period, LS-mean scores deteriorated in the placebo group but not in the LDX group. Compared with placebo, the effect of LDX was significant in the Family, Learning and School, and Risky Activities domains and in total (effect size 0.908; p < 0.001).. Using parent-rated instruments, long-term maintenance of the beneficial effect of LDX in multiple domains of health-related quality of life and functional impairment was demonstrated by comparison of treatment continuation and withdrawal under randomized, double-blind, placebo-controlled conditions.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Double-Blind Method; Europe; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Psychotropic Drugs; Quality of Life; Treatment Outcome

The relationship between attention-deficit/hyperactivity disorder (ADHD) symptoms and global clinical assessment of functionality is complex. This post-hoc analysis explores this relationship and suggests implications for patient assessment in clinical practice. Adults with ADHD on a stable lisdexamfetamine dimesylate (LDX) dose for ≥ 6 months were enrolled in a double-blind, placebo-controlled, randomized withdrawal study. Participants entered a 3-week open-label phase continuing their prior LDX dose and were then randomized to placebo or the same LDX dose for a 6-week, double-blind, randomized withdrawal phase. ADHD symptom distribution was measured by the ADHD Rating Scale IV (ADHD-RS-IV) with Adult Prompts total score reflecting DSM-IV-TR ADHD symptom criteria and severity by Clinical Global Impressions-Severity (CGI-S) ratings at study entry and at end of study. Of 123 participants enrolled in the open-label phase, 116 were included in the randomized withdrawal phase (placebo, n = 60; LDX, n = 56). As reported in a prior publication, mean (standard deviation) ADHD-RS-IV total score change from baseline (week 3) to end of study (randomized-withdrawal phase) was 16.8 (11.80) for placebo and 1.6 (8.63) for LDX. At end of study, for placebo and LDX, 5.0% and 32.1% of participants, respectively, had a CGI-S = 1, 11.7% and 35.7% had a CGI-S = 2, 11.7% and 17.9% had a CGI-S = 3, 33.3% and 7.1% had a CGI-S = 4, 35.0% and 7.1% had a CGI-S = 5, and 3.3% and 0% had a CGI-S = 6; no participants had a CGI-S = 7 (P < 0.0001). The CGI-S ratings increased (worsened) as ADHD symptom scores worsened. Post-hoc regression analysis between ADHD-RS-IV scores and CGI-S demonstrated shared variance of 47% at week 3 and 69% for both placebo and LDX at end of study. Although ADHD symptom scores demonstrate a linear relationship with global illness severity, the variance suggests that other factors not captured by symptom scales are also important in assessing patient outcomes in clinical practice. (. ClinicalTrials.gov NCT00877487.).

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Recurrence; Severity of Illness Index; Young Adult

The goal of this study was to assess the efficacy and tolerability of lis-dexamfetamine dimesylate (LDX) as an adjunct to nicotine replacement therapy in adult smokers with ADHD who were undergoing a quit attempt.. Thirty-two regular adult smokers with ADHD were randomized to receive LDX (n = 17) or placebo (n = 15) in addition to nicotine patch concurrent with a quit attempt.. There were no differences between smokers assigned to LDX versus placebo in any smoking outcomes. Participants treated with LDX demonstrated significant reductions in self-reported and clinician-rated ADHD symptoms. LDX was well tolerated in smokers attempting to quit.. In general, LDX does not facilitate smoking cessation in adults with ADHD more than does placebo, though both groups significantly reduced smoking. LDX demonstrated efficacy for reducing ADHD symptoms in adult smokers engaging in a quit attempt.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Pilot Projects; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Tobacco Use Disorder; Treatment Outcome

To evaluate the effect of lisdexamfetamine dimesylate (LDX) on emotional lability (EL) in children with ADHD.. Post hoc analyses of a placebo-controlled trial of LDX-stratified children (aged 6-12 years) with ADHD to prominent and not prominent EL at baseline (score >3 or ≤3, respectively, on Conners' Parent Rating Scale [CPRS] items of anger, loss of temper, and irritability). Efficacy was assessed by change in CPRS EL scores and ADHD Rating Scale-IV (ADHD-RS-IV) total and subscale scores. Safety measures included treatment-emergent adverse events (TEAEs).. LDX showed improvement versus placebo (p < .0005) for EL item least squares (LS) mean change scores at endpoint and throughout the day. At baseline, 138 and 73 participants randomized to LDX treatment and having baseline and endpoint CPRS scores were categorized with CPRS-derived prominent and not prominent baseline EL, respectively; 41 and 31 participants randomized to placebo were categorized with CPRS-derived prominent and not prominent baseline EL, respectively. ADHD-RS-IV total and subscale scores decreased with LDX regardless of baseline EL severity. TEAEs included decreased appetite, insomnia, upper abdominal pain, headache, and irritability.. EL and ADHD symptoms improved with LDX regardless of baseline EL symptom severity. LDX demonstrated a safety profile consistent with long-acting psychostimulant use.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Emotions; Female; Humans; Lisdexamfetamine Dimesylate; Male; Mood Disorders; Parents; Personality Assessment; Treatment Outcome

Information on psychostimulant treatment in long-term studies for attention-deficit/hyperactivity disorder (ADHD) in adolescents is limited. This study aimed to assess the safety and effectiveness of lisdexamfetamine dimesylate (LDX) over 52 weeks in adolescents with ADHD.. This open-label multicenter study enrolled eligible participants after their participation in a randomized, double-blind, placebo-controlled 4 week trial in adolescents with ADHD. Following a 4 week dose-optimization phase, participants were maintained on treatment for up to ∼48 weeks on an optimal dose. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, laboratory findings, and electrocardiograms. Effectiveness measures included the ADHD Rating Scale IV (ADHD-RS-IV; primary) and Clinical Global Impressions-Improvement (CGI-I). The Youth Quality of Life-Research Version (YQOL-R) was also included in this study; raw scores are transformed to a 0-100 point scale.. Of 269 enrolled (from the antecedent study), 265 (98.5%) were in the safety population and effectiveness population. Common TEAEs (≥5%) with LDX included upper respiratory tract infection (21.9%), decreased appetite (21.1%), headache (20.8%), decreased weight (16.2%), irritability (12.5%), insomnia (12.1%), nasopharyngitis (7.2%), influenza (6.8%), dizziness (5.3%), and dry mouth (5.3%). At end point, for all LDX doses in the overall safety population, mean (SD) increase from baseline in systolic blood pressure was 2.3 (10.53) mm Hg, diastolic blood pressure was 2.5 (8.37) mm Hg, and pulse rate was 6.3 (12.74) bpm. No clinically meaningful electrocardiogram or vital sign changes were observed. At end point with LDX treatment, the ADHD-RS-IV mean (SD) total score change from antecedent study baseline was -26.2 (9.75) (p<0.001); 87.2% of participants were improved (CGI-I=1 or 2). Baseline (antecedent study) mean (SD) YQOL-R perceptual total score was 79.8 (11.28) and increased by 3.9 (9.73) at end point (p<0.001).. LDX demonstrated a long-term safety profile similar to that of other long-acting psychostimulants and was effective, as indicated by improvements in ADHD symptoms and participant-perceived YQOL, in adolescents with ADHD.. NCT00764868, http://www.clinicaltrials.gov/ct2/show/NCT00764868?term=SPD489-306&rank=1.

Topics: Adolescent; Adolescent Behavior; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Quality of Life

The purpose of this article was to describe the relationships between parent-rated executive function (EF) and clinician-rated attention-deficit/hyperactivity disorder (ADHD) symptoms before and after lisdexamfetamine dimesylate (LDX) treatment in children with and without EF deficit.. In post-hoc analyses of children with ADHD who participated in a 7 week open-label, dose-optimized (LDX 20-70 mg/day) trial, ADHD Rating Scale-IV (ADHD-RS-IV) change scores were compared (using two-sample t tests) between youth with and without clinically significant EF impairment at baseline. Clinically significant impairment was defined as parent-rated Behavior Rating Inventory of EF (BRIEF) Global Executive Composite (GEC) t scores ≥65. Relationships between baseline and endpoint BRIEF and ADHD-RS-IV scores were examined using Pearson correlations and generalized effect linear model. Safety assessment included treatment-emergent adverse events (TEAEs).. At baseline, 265/315 participants (84.1%) had a clinically significant BRIEF score. Their mean (SD) ADHD-RS-IV total score at baseline was 42.1 (6.64) for those with, and 36.5 (6.67) for those without, clinically significant BRIEF. At endpoint, ADHD-RS-IV total and subscale scores were significantly improved (p<0.0001) for both those with and those without clinically significant baseline BRIEF scores. Moderately strong, positive Pearson correlations were observed between BRIEF and ADHD-RS-IV total and subscale scores. In the generalized effect linear model, ADHD-RS-IV change scores were significantly correlated with endpoint BRIEF scores (r(2)=0.35, β=0.73, p<0.0001). In the subgroup without clinically significant BRIEF t scores at endpoint, parents and clinicians rated 90% and 95%, respectively, as improved. In the subgroup with clinically significant BRIEF t scores at endpoint, parents and clinicians rated 69% and 78%, respectively, as improved. TEAEs were experienced by 269/318 (84.9%) participants; most (82.7%) experienced events mild to moderate in intensity. A total of 12/318 (4.1%) participants discontinued because of TEAEs.. Clinically significant impairment of EF behaviors in children with ADHD was associated with more severe ADHD symptoms. LDX therapy improved ADHD symptom severity, and at endpoint, fewer participants displayed impairment of EF behaviors (versus baseline). The parent-rated BRIEF may describe clinically important EF behaviors not assessed by the 18-item ADHD-RS-IV.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child Behavior; Dextroamphetamine; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Parents; Psychiatric Status Rating Scales

Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Post hoc subgroup analyses were performed from two studies in children with ADHD to compare the efficacy of LDX in participants who had received prior methylphenidate (MPH) treatment with that of the overall study populations.. Study 1 (7-week; open-label design) and study 2 (randomized, double-blind, placebo-controlled, crossover, laboratory school design) enrolled children aged 6-12 years with ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Both studies excluded children whose prestudy ADHD treatment provided effective control of ADHD symptoms with an acceptable safety profile. Post hoc efficacy analyses were performed in children who had received MPH within 6 months of study enrollment. Efficacy measures included the following scales: ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), Behavior Rating Inventory of Executive Function (BRIEF), Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), and Permanent Product Measure of Performance (PERMP).. In studies 1 and 2, 83/318 (26%) and 67/129 (52%) participants, respectively, had received MPH within 6 months and were not adequately controlled on current medication with acceptable tolerability; most of these participants had received long-acting MPH. In prior MPH participants, efficacy assessments demonstrated improvements from baseline (study 1) and versus placebo (study 2) that were comparable with those seen in the respective overall study population. Safety profiles were consistent with long-acting stimulant use.. In two studies, children who had received prior MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study populations. For children with ADHD who were previously treated with MPH, LDX may, therefore, be an efficacious treatment option.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Prodrugs; Treatment Outcome

There are limited head-to-head data comparing the efficacy of long-acting amfetamine- and methylphenidate-based psychostimulants as treatments for individuals with attention-deficit hyperactivity disorder (ADHD). This post hoc analysis provides the first parallel-group comparison of the effect of lisdexamfetamine dimesylate (lisdexamfetamine) and osmotic-release oral system methylphenidate (OROS-MPH) on symptoms of ADHD in children and adolescents.. This was a post hoc analysis of a randomized, double-blind, parallel-group, dose-optimized, placebo-controlled, phase III study.. The phase III study was carried out in 48 centres across ten European countries.. The phase III study enrolled children and adolescents (aged 6-17 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for a primary diagnosis of ADHD and who had a baseline ADHD Rating Scale IV (ADHD-RS-IV) total score of 28 or higher.. Eligible patients were randomized (1:1:1) to receive a once-daily, optimized dose of lisdexamfetamine (30, 50 or 70 mg/day), placebo or OROS-MPH (18, 36 or 54 mg/day) for 7 weeks.. In this post hoc analysis, efficacy was assessed using the ADHD-RS-IV and Clinical Global Impressions-Improvement (CGI-I) scale. Responders were defined as those achieving at least a 30% reduction from baseline in ADHD-RS-IV total score and a CGI-I score of 1 (very much improved) or 2 (much improved). The proportion of patients achieving an ADHD-RS-IV total score less than or equal to the mean for their age (based on normative data) was also determined. Endpoint was the last on-treatment visit with a valid assessment. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.. Of the 336 patients randomized, 332 were included in the safety population, 317 were included in the full analysis set and 196 completed the study. The mean (standard deviation) ADHD-RS-IV total score at baseline was 40.7 (7.31) for lisdexamfetamine, 41.0 (7.14) for placebo and 40.5 (6.72) for OROS-MPH. The least-squares (LS) mean change (standard error) in ADHD-RS-IV total score from baseline to endpoint was -24.3 (1.16) for lisdexamfetamine, -5.7 (1.13) for placebo and -18.7 (1.14) for OROS-MPH. The difference between lisdexamfetamine and OROS-MPH in LS mean change (95% confidence interval [CI]) in ADHD-RS-IV total score from baseline to endpoint was statistically significant in favour of lisdexamfetamine (-5.6 [-8.4 to -2.7]; p < 0.001). The difference between lisdexamfetamine and OROS-MPH in the percentage of patients (95% CI) with a CGI-I score of 1 or 2 at endpoint was 17.4 (5.0-29.8; p < 0.05; number needed to treat [NNT] 6), and the difference in the percentage of patients (95% CI) achieving at least a 30% reduction in ADHD-RS-IV total score and a CGI-I score of 1 or 2 was 18.3 (5.4-31.3; p < 0.05; NNT 6). The difference between lisdexamfetamine and OROS-MPH in the percentage of patients (95% CI) with an ADHD-RS-IV total score less than or equal to the mean for their age at endpoint was 14.0 (0.6-27.4; p = 0.050). The overall frequency of TEAEs and the frequencies of decreased appetite, insomnia, decreased weight, nausea and anorexia TEAEs were greater in patients treated with lisdexamfetamine than in those treated with OROS-MPH, whereas headache and nasopharyngitis were more frequently reported in patients receiving OROS-MPH.. This post hoc analysis showed that, at the doses tested, patients treated with lisdexamfetamine showed statistically significantly greater improvement in symptoms of ADHD than those receiving OROS-MPH, as assessed using the ADHD-RS-IV and CGI-I. The safety profiles of lisdexamfetamine and OROS-MPH were consistent with the known effects of stimulant medications.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate

Optimal management of attention deficit hyperactivity disorder (ADHD) aims not only to ameliorate patients' symptoms, but also to improve health-related quality of life (HRQL) and functioning. A pivotal, 7-week, randomized, double-blind, placebo-controlled, phase III study in children and adolescents in ten European countries demonstrated that the stimulant prodrug lisdexamfetamine dimesylate (LDX) is an effective and generally well-tolerated treatment for symptoms of ADHD.. The aim of this study was to assess HRQL and functional impairment outcomes in this clinical trial, using the Child Health and Illness Profile-Child Edition: Parent Report Form (CHIP-CE:PRF) and the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P), respectively.. Patients (aged 6-17 years) with diagnosed ADHD and a baseline ADHD Rating Scale IV total score ≥28 were randomized (1:1:1) to 7 weeks of double-blind treatment with once-daily LDX, placebo or the reference treatment, osmotic-release oral system methylphenidate (OROS-MPH). Participants' parents (or legally authorized representatives) completed the CHIP-CE:PRF and WFIRS-P questionnaires at baseline, at weeks 4 and 7, and/or at early termination. Endpoint was defined as the last on-treatment visit with valid data (≤30 % missing items). The CHIP-CE:PRF Achievement domain was pre-specified as the primary HRQL outcome.. The full analysis set comprised 317 patients (LDX, n = 104; placebo, n = 106; OROS-MPH, n = 107), the majority of whom completed the study (LDX, n = 77; placebo, n = 42; OROS-MPH, n = 72). Baseline CHIP-CE:PRF T-scores in four of the five domains were ≥1 standard deviation below norms (US community samples). Compared with placebo, LDX was associated with statistically significantly improved T-scores from baseline to endpoint in these four domains, with effect sizes of 1.280 (p < 0.001) in Achievement, 1.079 (p < 0.001) in Risk Avoidance, 0.421 (p < 0.01) in Resilience and 0.365 (p < 0.05) in Satisfaction. In LDX-treated patients, placebo-adjusted improvements from baseline to endpoint in WFIRS-P scores were statistically significant (p < 0.001) for total score and four of the six domains, with effect sizes of 0.924 (total score), 1.249 (Learning and School), 0.730 (Family), 0.643 (Social Activities) and 0.640 (Risky Activities). OROS-MPH treatment showed similar patterns of improvement from baseline to endpoint in both CHIP-CE:PRF and WFIRS-P scores.. Baseline HRQL and functional impairment scores reflect the burden of untreated ADHD. The benefits of short-term stimulant treatment in children and adolescents with ADHD extend beyond symptomatic relief and impact positively on HRQL and daily functioning.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Double-Blind Method; Drug Administration Schedule; Educational Status; Female; Humans; Lisdexamfetamine Dimesylate; Male; Quality of Life; Surveys and Questionnaires; Treatment Outcome

Behavioral rating scales that assess impairments in executive function commonly associated with attention-deficit/hyperactivity disorder (ADHD) may offer advantages over neuropsychological testing. The primary objective of this study was to evaluate the efficacy of lisdexamfetamine dimesylate for executive function deficits in adults with ADHD and clinically significant executive function impairment using self-reported Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A) assessments.. This randomized double-blind study, conducted between May 2010 and November 2010, screened at least 1 participant at 35 of 39 registered US clinical research sites. Adults (aged 18-55 years) with a primary ADHD diagnosis (meeting full DSM-IV-TR criteria) and executive function deficits (assessed by baseline BRIEF-A Global Executive Composite [GEC] T-scores of at least 65) were randomized to treatment with optimized lisdexamfetamine dimesylate (30 mg/d, 50 mg/d, or 70 mg/d; n = 80) or placebo (n = 81) during a 10-week double-blind treatment period. Outcome measures included the BRIEF-A scales (GEC, index, and clinical subscales).. At week 10 or at early termination, lisdexamfetamine dimesylate was associated with significantly greater reductions from baseline in mean BRIEF-A GEC T-scores than placebo (effect size, 0.74; P < .0001) and significantly greater reductions from baseline in mean T-scores for both BRIEF-A index scales (Behavioral Regulation Index and Metacognition Index) and all 9 clinical subscales (P ≤ .0056 for all). At week 10 or at early termination, mean T-scores for BRIEF-A indexes and clinical subscales were below levels of clinically significant executive function deficits (ie, < 65) with lisdexamfetamine dimesylate treatment. The mean (SD) GEC T-score was 57.2 (14.11) for the lisdexamfetamine dimesylate group and 68.3 (17.12) for the placebo group. The safety profile of lisdexamfetamine dimesylate was consistent with other long-acting psychostimulants.. Among adults with ADHD and clinically significant executive function deficits, lisdexamfetamine dimesylate was associated with significant improvements in self-reported executive function ratings.. ClinicalTrials.gov identifier: NCT01101022.

Topics: Adult; Attention; Attention Deficit Disorder with Hyperactivity; Behavioral Symptoms; Central Nervous System Stimulants; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Monitoring; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Neuropsychological Tests; Psychiatric Status Rating Scales; Self-Assessment; Treatment Outcome

The purpose of this study was to assess lisdexamfetamine dimesylate (LDX) treatment effects based on baseline emotional control dysfunction in children with attention-deficit/hyperactivity disorder (ADHD) categorized with or without impairments of executive function (EF) emotional control.. Post-hoc analyses of a 7 week, open-label LDX study in children with ADHD (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision [DSM-IV-TR] defined) and impairments in EF control of emotional response. At baseline, participants were dichotomized by Behavior Rating Inventory of EF (BRIEF) emotional control domain T-scores of ≥65 (with impairment) or <65 (without impairment). ADHD Rating Scale-IV (ADHD-RS-IV), BRIEF Global Executive Composite and emotional control domain, Expression and Emotion Scale for Children (EESC) scores, Pearson correlations for BRIEF versus ADHD-RS-IV and EESC, and Clinical Global Impressions scores were assessed at baseline and end of study (week 7)/early termination (EOS/ET) by baseline category of BRIEF emotional control impairment. Safety assessments included treatment-emergent adverse events (TEAEs).. At baseline and EOS/ET, respectively, 53.0% and 20.7% met criteria for emotional control impairment. Participants with and without emotional control impairments had similar ADHD-RS-IV change scores. Mean (SD) change from baseline for those with and without emotional control impairments were -20.8 (12.89) and -14.6 (11.25) for BRIEF global scores and -16.0 (13.19) and -5.0 (9.48) for BRIEF emotional control domain scores. Participants with emotional control impairments had greater mean EESC total score changes. BRIEF emotional control domain and all ADHD-RS-IV scores indicated moderate correlations between change scores (all p<0.0001). Overall, 84.9% of participants had TEAEs (mostly mild-to-moderate in severity); 3.8% discontinued because of TEAEs.. The proportion of children with behavioral impairments in EF control of emotional response decreased during LDX treatment. ADHD symptoms improved in both groups. The moderate correlations between EF behaviors and ADHD symptoms suggest there may be utility in evaluating behavioral domains beyond core ADHD symptoms.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Emotions; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome

The aim of this study was to compare the efficacy and safety of the prodrug psychostimulant lisdexamfetamine dimesylate (LDX) and the non-stimulant noradrenergic compound atomoxetine (ATX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who had previously responded inadequately to methylphenidate (MPH).. This 9-week, head-to-head, randomized, double-blind, active-controlled study (SPD489-317; ClinicalTrials.gov NCT01106430) enrolled patients (aged 6-17 years) with at least moderately symptomatic ADHD and an inadequate response to previous MPH therapy. Patients were randomized (1:1) to an optimized daily dose of LDX (30, 50 or 70 mg) or ATX (patients <70 kg, 0.5-1.2 mg/kg with total daily dose not to exceed 1.4 mg/kg; patients ≥70 kg, 40, 80 or 100 mg). The primary efficacy outcome was time (days) to first clinical response. Clinical response was defined as a Clinical Global Impressions-Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved). Secondary efficacy outcomes included the proportion of responders at each study visit and the change from baseline in ADHD Rating Scale (ADHD-RS-IV) and CGI-Severity scores. Tolerability and safety were assessed by monitoring treatment-emergent adverse events (TEAEs), height and weight, vital signs and electrocardiogram parameters. Endpoint was defined as the last post-baseline, on-treatment visit with a valid assessment.. Of 267 patients randomized (LDX, n = 133; ATX, n = 134), 200 (74.9%) completed the study. The median time to first clinical response [95% confidence interval (CI)] was significantly shorter for patients receiving LDX [12.0 days (8.0-16.0)] than for those receiving ATX [21.0 days (15.0-23.0)] (p = 0.001). By week 9, 81.7% (95% CI 75.0-88.5) of patients receiving LDX had responded to treatment compared with 63.6% (95% CI 55.4-71.8) of those receiving ATX (p = 0.001). Also by week 9, the difference between LDX and ATX in least-squares mean change from baseline (95% CI) was significant in favour of LDX for the ADHD-RS-IV total score [-6.5 (-9.3 to -3.6); p < 0.001; effect size 0.56], inattentiveness subscale score [-3.4 (-4.9 to -1.8); p < 0.001; effect size 0.53] and the hyperactivity/impulsivity subscale score [-3.2 (-4.6 to -1.7); p < 0.001; effect size 0.53]. TEAEs were reported by 71.9 and 70.9% of patients receiving LDX and ATX, respectively. At endpoint, both treatments were associated with mean (standard deviation) increases in systolic blood pressure [LDX, +0.7 mmHg (9.08); ATX, +0.6 mmHg (7.96)], diastolic blood pressure [LDX, +0.1 mmHg (8.33); ATX, +1.3 mmHg (8.24)] and pulse rate [LDX, +3.6 bpm (10.49); ATX, +3.7 bpm (10.75)], and decreases in weight [LDX, -1.30 kg (1.806); ATX, -0.15 kg (1.434)].. LDX was associated with a faster and more robust treatment response than ATX in children and adolescents with at least moderately symptomatic ADHD who had previously responded inadequately to MPH. Both treatments displayed safety profiles consistent with findings from previous clinical trials.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Propylamines; Treatment Outcome

We primarily sought to determine the effect of adjunctive lisdexamfetamine dimesylate (LDX) on anthropometric and metabolic parameters. Our secondary aim was to evaluate the effect of LDX on attention deficit hyperactivity disorder (ADHD) symptom severity in adults with bipolar I/II disorder.. Forty-five stable adults (i.e., non-rapid cycling, absence of clinically significant hypo/manic symptoms) with bipolar I/II disorder and comorbid ADHD were enrolled in a phase IV, 4-week, flexible dose, open-label study of adjunctive LDX. All subjects were initiated at 30 mg/day of adjunctive LDX for the first week with flexible dosing (i.e., 30-70 mg/day) between weeks 2 and 4.. Of the 45 subjects enrolled, 40 received adjunctive LDX (mean dose = 60 ± 10 mg/day). A statistically significant decrease from baseline to endpoint was evident in weight (p < 0.001), body mass index (p < 0.001), fasting total cholesterol (p = 0.011), low density lipoprotein cholesterol (p = 0.044), high density lipoprotein cholesterol (p = 0.015) but not triglycerides, or blood glucose. Significant reductions were also observed in leptin (p = 0.047), but not in ghrelin, adiponectin, or resistin levels. Diastolic blood pressure and pulse increased significantly over time but on average remained within the normal range (p < 0.001). There was a significant reduction from baseline to endpoint in the total score of the ADHD Self-Report Scale. Significant improvement from baseline to endpoint was also observed in the Montgomery-Åsberg Depression Rating Scale total score as well as the Clinical Global Impression Severity and Improvement score.. Short-term adjunctive LDX treatment was well tolerated by this sample of adults with stable bipolar I/II disorder. Lisdexamfetamine dimesylate offered beneficial effects on body weight, body mass index and several metabolic parameters. In addition to demonstrating short-term (i.e., 4 weeks) safety and tolerability, beneficial effects of LDX were also observed in mitigating depressive and ADHD symptom severity.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Bipolar Disorder; Body Weight; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Treatment Outcome; Young Adult

This study examined the effects of lisdexamfetamine dimesylate (LDX) on quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) and clinically significant executive function deficits (EFD).. This report highlights QOL findings from a 10-week randomized placebo-controlled trial of LDX (30-70 mg/d) in adults (18-55 years) with ADHD and EFD (Behavior Rating Inventory of EF-Adult, Global Executive Composite [BRIEF-A GEC] ≥65). The primary efficacy measure was the self-reported BRIEF-A; a key secondary measure was self-reported QOL on the Adult ADHD Impact Module (AIM-A). The clinician-completed ADHD Rating Scale version IV (ADHD-RS-IV) with adult prompts and Clinical Global Impressions-Severity (CGI-S) were also employed. The Adult ADHD QoL (AAQoL) was added while the study was in progress. A post hoc analysis examined the subgroup having evaluable results from both AIM-A and AAQoL.. Of 161 randomized (placebo, 81; LDX, 80), 159 were included in the safety population. LDX improved AIM-A multi-item domain scores versus placebo; LS mean difference for Performance and Daily Functioning was 21.6 (ES, 0.93, P<.0001); Impact of Symptoms: Daily Interference was 14.9 (ES, 0.62, P<.0001); Impact of Symptoms: Bother/Concern was 13.5 (ES, 0.57, P=.0003); Relationships/Communication was 7.8 (ES, 0.31, P=.0302); Living With ADHD was 9.1 (ES, 0.79, P<.0001); and General Well-Being was 10.8 (ES, 0.70, P<.0001). AAQoL LS mean difference for total score was 21.0; for subscale: Life Productivity was 21.0; Psychological Health was 12.1; Life Outlook was 12.5; and Relationships was 7.3. In a post hoc analysis of participants with both AIM-A and AAQoL scores, AIM-A multi-item subgroup analysis scores numerically improved with LDX, with smaller difference for Impact of Symptoms: Daily Interference. The safety profile of LDX was consistent with amphetamine use in previous studies.. Overall, adults with ADHD/EFD exhibited self-reported improvement on QOL, using the AIM-A and AAQoL scales in line with medium/large ES; these improvements were paralleled by improvements in EF and ADHD symptoms. The safety profile of LDX was similar to previous studies.. ClinicalTrials.gov, NCT01101022.

Topics: Activities of Daily Living; Adult; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Neuropsychological Tests; Quality of Life; Self Report; Treatment Outcome

This study evaluated the efficacy and safety of lisdexamfetamine dimesylate (LDX) compared with placebo in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in Europe. Osmotic-release oral system methylphenidate (OROS-MPH) was included as a reference arm. Patients (6-17 years old) with a baseline ADHD Rating Scale version IV (ADHD-RS-IV) total score ≥ 28 were randomized (1:1:1) to dose-optimized LDX (30, 50, or 70 mg/day), OROS-MPH (18, 36, or 54 mg/day) or placebo for 7 weeks. Primary and key secondary efficacy measures were the investigator-rated ADHD-RS-IV and the Clinical Global Impressions-Improvement (CGI-I) rating, respectively. Safety assessments included treatment-emergent adverse events (TEAEs), electrocardiograms, and vital signs. Of 336 patients randomized, 196 completed the study. The difference between LDX and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -18.6 (95% confidence interval [CI]: -21.5 to -15.7) (p<0.001; effect size, 1.80). The difference between OROS-MPH and placebo in least squares mean change in ADHD-RS-IV total score from baseline to endpoint was -13.0 (95% CI: -15.9 to -10.2) (p<0.001; effect size, 1.26). The proportions (95% CI) of patients showing improvement (CGI-I of 1 or 2) at endpoint were 78% (70-86), 14% (8-21), and 61% (51-70) for LDX, placebo, and OROS-MPH. The most common TEAEs for LDX were decreased appetite, headache, and insomnia. Mean changes in vital signs were modest and consistent with the known profile of LDX. LDX was effective and generally well tolerated in children and adolescents with ADHD.

Topics: Adolescent; Adolescent Behavior; Appetite Regulation; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child Behavior; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Drug Resistance; Europe; Female; Follow-Up Studies; Humans; Impulsive Behavior; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Patient Dropouts; Psychiatric Status Rating Scales; Severity of Illness Index

Despite the overall high degree of response to pharmacotherapy, consensus is lacking on how to judge clinical response or define optimal treatment/remission when treating adults with attention-deficit/hyperactivity disorder (ADHD). This study examined clinical response and symptomatic remission in analyses of 2 studies of lisdexamfetamine dimesylate (LDX) in adults with ADHD.. In a 4-week, double-blind, forced-dose trial, adults with ADHD were randomized to LDX 30, 50, and 70 mg/day (mg/d) or placebo. In a second, open-label, follow-up trial, adults entering from the 4-week study were titrated to an "optimal" LDX dose (30 mg/d [n=44], 50 mg/d [n=112], and 70 mg/d [n=171]) over 4 weeks, and maintained for 11 additional months. The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts and the Clinical Global Impressions-Improvement (CGI-I) scale assessed efficacy. Clinical response was defined, post hoc, as ≥30% reduction from baseline in ADHD-RS-IV and CGI-I rating of 1 or 2; symptomatic remission was defined as ADHD-RS-IV total score ≤18. Log rank analysis examined overall significance among the treatment groups in time to response or remission.. Four hundred and fourteen participants in the 4-week study and 345 in the open-label, extension study were included in the efficacy populations. All LDX groups improved by ADHD-RS-IV and CGI-I scores in both studies. In the 4-week study (n=414), 69.3% responded and 45.5% achieved remission with LDX (all doses); 37.1% responded and 16.1% achieved remission with placebo; time (95% CI) to median clinical response (all LDX doses) was 15.0 (15.0, 17.0) days and to remission was 31.0 (28.0, 37.0) days (P<.0001 overall). In the open-label study, with LDX (all doses), 313 (95.7%) and 278 (85.0%) of 327 participants with evaluable maintenance-phase data met criteria for response and remission, respectively. Of participants who completed dose optimization, 75.2% remained responders and 65.7% remained in remission in the 12-month study. Overall, 285 (82.6%) and 227 (65.8%) of 345 participants were responders and remitters, respectively, at their final visits.. In the long-term study, with open-label, dose-optimized LDX treatment, most adults with ADHD achieved clinical response and/or symptomatic remission; almost two-thirds maintained symptomatic remission over the remaining 11 months.. Clinical Trial Numbers: NCT00334880 and NCT01070394CLINICAL TRIAL REGISTRY: clinicaltrials.gov.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Female; Humans; Kaplan-Meier Estimate; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Remission Induction; Treatment Outcome

To describe clinically relevant effects of lisdexamfetamine dimesylate (LDX) on emotional expression (EE) in children with ADHD.. Children with ADHD participated in a 7-week, open-label, LDX dose-optimization study. Expression and Emotion Scale for Children (EESC) change scores were analyzed post hoc using two methods to determine proportion of participants with different categories of clinical response based on (a) clinically significant (movement >2 SD from baseline mean)/reliable change (not due to measurement error) and (b) standard error of measurement (SEM) as a measure of clinically meaningful change.. With LDX, no participants showed clinically significant/reliable improvement; 0.7% showed clinically significant/reliable deterioration of EE by reliable change index and movement from baseline mean. One third of participants had improved EE by SEM criteria; 9.2% had categorical worsening.. Using clinically meaningful change and clinically significant/reliable change categories derived from the EESC, most participants had no worsening of EE with LDX.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Emotions; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Treatment Outcome

To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD.. This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) criteria for ADHD.. Nearly all participants assigned to an LDX dose achieved their assigned dose with the exception of about 4% of participants assigned to the 50 mg or 14% assigned to the 70 mg doses. Higher doses of LDX led to greater improvements in ADHD-rating scale scores, independent of prior pharmacotherapy. This was evident for both inattentive and hyperactive-impulsive symptoms. The authors found some evidence for an interaction between LDX dose and baseline severity of ADHD symptoms.. For LDX doses between 30 and 70 mg/d, the dose-response efficacy effect for LDX is not affected by prior pharmacotherapy, but patients with a greater severity of illness may benefit more from higher doses, especially for hyperactive-impulsive symptoms. The results do not provide information about doses above 70 mg/d, which is the maximum approved dose of LDX and the highest dose studied in ADHD clinical trials.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Treatment Outcome

To evaluate stimulant medication on symptoms and functioning for college students with ADHD using double-blind, placebo-controlled, crossover design.. Participants included 24 college students with ADHD and 26 college students without psychopathology. Lisdexamfetamine dimesylate (LDX) was examined for ADHD participants over five weekly phases (no-drug baseline, placebo, 30-, 50-, and 70-mg LDX per day). Self-report rating scales of functioning and direct assessment of ADHD symptoms, verbal learning/memory, and adverse side effects were collected (baseline only for control students).. LDX was associated with large reductions in ADHD symptoms and improvement in executive functioning along with smaller effects for psychosocial functioning. Reduction in ADHD symptoms was found for 86.4% of participants; however, large differences in symptoms and executive functioning remained relative to controls.. LDX is a safe, efficacious treatment for symptom relief in college students with ADHD. Research documenting medication effects on academic functioning and evaluating psychosocial/educational interventions is needed.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Executive Function; Female; Humans; Learning; Lisdexamfetamine Dimesylate; Male; Neuropsychological Tests; Students; Treatment Outcome; Universities; Young Adult

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Female; Humans; Lisdexamfetamine Dimesylate; Male; Sex Factors

Young adults with Attention Deficit Hyperactivity Disorder (ADHD) have been shown to be at increased risk for impairment in driving behaviors. While stimulant medications have proven efficacy in reducing ADHD symptomatology, there is limited knowledge as to their effects on driving impairment. The main aim of this study was to assess the impact of lisdexamfetamine dimesylate (LDX) on driving performance in young adults with ADHD using a validated driving simulation paradigm. This was a randomized, double-blind, 6-week, placebo-controlled, parallel-design study of LDX vs. a placebo on driving performance in a validated driving simulation paradigm. Subjects were sixty-one outpatients of both sexes, 18-26 years of age, who met DSM-IV criteria for ADHD. Subjects were randomized to receive LDX or placebo after a baseline driving simulation and completed a second driving simulation six weeks after beginning drug or placebo. Examination of reaction time across five surprise events at post-treatment showed a significant positive effect of medication status. LDX treatment was also associated with significantly fewer accidents vs. placebo. LDX treatment was associated with significantly faster reaction times and a lower rate of simulated driving collisions than placebo. These results suggest that LDX may reduce driving risks in young adults with ADHD.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Automobile Driving; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychomotor Performance; Treatment Outcome; User-Computer Interface; Young Adult

To evaluate the type, frequency, duration, and severity of treatment emergent adverse events (TEAEs) of the prodrug lisdexamfetamine dimesylate (LDX) in children with and without previous exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD).. This single-blind, modified laboratory school study used open-label, dose optimization of children aged 6-12 years. LDX, initiated at 30 mg, was dose titrated in 20 mg increments to a possible 70 mg over 4-5 weeks. Safety was assessed using adverse effects and LDX levels.. Twenty-eight subjects enrolled in the study, with 27 safety protocol completers (n=14 previous stimulant exposure; n=13 stimulant naïve). The stimulant-naïve group reported more trouble sleeping, stomach pain, and hyperfocus, but only previous-exposure subjects experienced dizziness. Previous-exposure subjects showed trends of more decreased appetite, less talkativeness, and less lip sucking. There were no differences in the mean duration of TEAEs. The epidemiological method of percent person-weeks applied to ADHD treatment offers a novel approach to interpreting the pattern of TEAEs.. LDX reduced the core symptoms of ADHD with more severe adverse events in stimulant-naïve than previous-exposure subjects. Future controlled studies with larger samples should address the impact of previous stimulant exposure on other ADHD treatments.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Female; Humans; Lisdexamfetamine Dimesylate; Male; Single-Blind Method

To evaluate lisdexamfetamine dimesylate maintenance of efficacy in adults with attention-deficit/hyperactivity disorder (ADHD).. Adults (aged 18-55 years) who had ADHD meeting DSM-IV-TR criteria, baseline ADHD Rating Scale-IV (ADHD-RS-IV) with adult prompts total scores of < 22, and Clinical Global Impressions-Severity of Illness (CGI-S) ratings of 1, 2, or 3 were enrolled. After previously receiving commercially available lisdexamfetamine dimesylate (30, 50, or 70 mg/d) for ≥ 6 months with acceptable tolerability and maintaining response during a 3-week open-label phase at a stable lisdexamfetamine dimesylate dose, the participants entered a 6-week double-blind randomized withdrawal phase on treatment with lisdexamfetamine dimesylate (same dose) or placebo. Data were collected from April 2009 to July 2010. The primary outcome was the proportion of participants having symptom relapse (≥ 50% increase in ADHD-RS-IV score and ≥ 2 rating-point increase in CGI-S score).. A total of 116 participants were randomized (lisdexamfetamine dimesylate n = 56; placebo n = 60). At the randomized withdrawal phase baseline, mean (SD) ADHD-RS-IV scores for lisdexamfetamine dimesylate and placebo were 10.6 (4.96) and 10.6 (4.82), respectively. At endpoint, 8.9% (5/56) of adults taking lisdexamfetamine dimesylate and 75.0% (45/60) taking placebo (P < .0001) showed symptom relapse; most showed relapse after 1 and 2 weeks of the randomized withdrawal phase (4 and 0 adults taking lisdexamfetamine dimesylate, 26 and 10 taking placebo, respectively). During the randomized withdrawal phase, treatment-emergent adverse events were reported in 48.2% and 30.0% of participants in the lisdexamfetamine dimesylate and placebo groups, respectively. Treatment-emergent adverse events with incidence ≥ 5% in the lisdexamfetamine dimesylate and placebo groups were headache (14.3% and 5.0%), insomnia (5.4% and 5.0%), and upper respiratory tract infection (8.9% and 0%).. In adults with ADHD on medium- to long-term treatment, lisdexamfetamine dimesylate demonstrated maintenance of efficacy vs placebo upon randomized withdrawal. A majority of patients given placebo showed symptom relapse by 2 weeks. The safety profile of lisdexamfetamine dimesylate was generally consistent with previous lisdexamfetamine dimesylate studies.. ClinicalTrials.gov identifier: NCT00877487.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Long-Term Care; Male; Secondary Prevention; Substance Withdrawal Syndrome; Treatment Outcome; Young Adult

Young adults with ADHD have been shown to be at increased risk for impairment in driving behaviors. Although stimulant medications have proven efficacy in reducing ADHD symptomatology, there is limited knowledge as to their effects on driving behavior. The focus of this report is on assessing the impact of lisdexamfetamine dimesylate (LDX) on driving behaviors in young adults with ADHD using a validated driving behavior questionnaire.. This assessment was carried out in the context of a randomized, double-blind, 6-week, placebo-controlled, parallel-design study of LDX versus placebo. Subjects were 61 outpatients of both sexes, 18-26 years of age, who met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects were randomized to receive LDX or placebo for 6 weeks. Driving behavior was assessed at baseline and at the end of treatment using a U.S. version of the Manchester Driving Behavior Questionnaire (DBQ).. Highly significant improvements were documented on LDX, over placebo, in driving behaviors assessed through the DBQ in measures of driving errors, driving lapses, and a trend toward fewer driving violations. There were no meaningful associations between these DBQ results and previously documented changes in a laboratory driving simulation paradigm or with improvement in symptoms of ADHD assessed through the ADHD rating scale.. LDX treatment was associated with significant improvements in self-reported driving behaviors that were independent of improvement in symptoms of ADHD. These results suggest that LDX may reduce behaviors associated with driving risks in young adults with ADHD.

Topics: Adolescent; Adult; Attention; Attention Deficit Disorder with Hyperactivity; Automobile Driving; Central Nervous System Stimulants; Computer Simulation; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Massachusetts; Psychomotor Performance; Surveys and Questionnaires; Young Adult

The beneficial effects of pharmacotherapy on children with attention-deficit hyperactivity disorder (ADHD) are well documented. We use near-infrared spectroscopy (NIRS) methodology to determine reorganization of brain neurovascular properties following the medication treatment. Twenty-six children with ADHD (ages six through 12) participated in a modified laboratory school protocol to monitor treatment response with lisdexamfetamine dimesylate (LDX; Vyvanse®, Shire US Inc.). All children refrained from taking medication for at least two weeks (washout period). To detect neurovascular reorganization, we measured changes in synchronization of oxy (HbO2) and deoxy (HHb) hemoglobin waves between the two frontal lobes. Participants without medication displayed average baseline HbO2 phase difference at about -7-deg. and HHb differences at about 240-deg.. This phase synchronization index changed after pharmacological intervention. Medication induced an average phase changes of HbO2 after first medication to 280-deg. and after medication optimization to 242-deg.. Instead first medication changed of the average HHb phase difference at 186-deg. and then after medication optimization to 120-deg. In agreement with findings of White et al., and Varela et al., we associated the phase synchronization differences of brain hemodynamics in children with ADHD with lobe specific hemodynamic reorganization of HbO2- and HHB oscillations following medication status.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cortical Synchronization; Dextroamphetamine; Female; Frontal Lobe; Humans; Lisdexamfetamine Dimesylate; Male; Oxygen; Oxygen Consumption; Spectroscopy, Near-Infrared; Statistics as Topic; Treatment Outcome

To examine the efficacy of lisdexamfetamine dimesylate (LDX) in adults with attention-deficit/hyperactivity disorder (ADHD) who remained symptomatic (ADHD Rating Scale IV [ADHD-RS-IV] total score >18) on amphetamine (AMPH) therapy (mixed AMPH salts and/or d-AMPH formulations) prior to enrollment in a 4-week placebo-controlled LDX trial vs the overall study population. In these post hoc analyses from a multicenter, randomized, double-blind, forced-dose titration study, clinical efficacy of LDX (30-70 mg/d) in adults with ADHD receiving AMPH treatment at screening vs the overall study population was evaluated. ADHD symptoms were assessed using the ADHD-RS-IV with adult prompts at screening, baseline (after prior treatment washout), and endpoint. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, laboratory findings, and electrocardiogram.. Of 414 participants (62, placebo; 352, LDX) included in the overall study population, 41 were receiving AMPH therapy at screening (2, placebo; 39, LDX); mean AMPH dose was 35.0 and 34.1 mg/d for participants in placebo and all LDX groups, respectively. Of the 41 participants, 36 remained symptomatic (ADHD-RS-IV >18) at screening despite receiving AMPH. For the 36 participants in the placebo (n = 2) and LDX (n = 34) groups, respectively, at endpoint, mean change from screening ADHD-RS-IV total scores were -5.5 and -14.8 and from baseline scores were -13.5 and -17.8. For the overall study population, endpoint mean change from baseline ADHD-RS-IV total scores were -7.8 for placebo and -17.5 for LDX. In the prior AMPH subgroup, 2/2 (100.0%) in the placebo group and 22/39 (56.4%) participants in the LDX (all doses) group reported any TEAE. Events that occurred in ≥5% for LDX were dry mouth (5/39; 12.8%), headache (5/39; 12.8%), fatigue (3/39; 7.7%), insomnia (3/39; 7.7%), decreased appetite (2/39; 5.1%), and nausea (2/39; 5.1%). None of these events occurred in the 2 placebo patients with prior AMPH use.. In these post hoc analyses, adults with significant baseline ADHD symptoms despite adequate AMPH treatment dose showed similar improvements in ADHD symptoms with LDX treatment as the overall study population. Prospective studies are needed to confirm these findings. The safety profile of LDX in the overall study population was consistent with long-acting psychostimulant use.. Study to Assess the Safety and Efficacy of NRP104 in Adults With Attention-Deficit Hyperactivity Disorder (ADHD). Clinicaltrials.gov Identifier: NCT00334880.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Data Interpretation, Statistical; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug Substitution; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Psychiatric Status Rating Scales; Surveys and Questionnaires; Treatment Outcome; Young Adult

This study evaluated the potential effects of short-term treatment with lisdexamfetamine dimesylate (LDX) on both subjective and objective sleep characteristics in children aged 6 to 12 years (n = 24) with ADHD.. Polysomnography (PSG) and actigraph measures as well as assessments of subjective sleep parameters were examined in children before and after treatment with either LDX or placebo in a randomized, double-blind, single-center, parallel-group study.. There was no statistically significant increase in the primary endpoint of latency to persistent sleep (LPS) for the LDX-treated group compared to the placebo group. Secondary PSG or actigraph results generally supported primary endpoint results. Subjective sleep measure results indicated the possibility that responses are influenced by sleep hygiene counseling before and throughout the study.. In this pilot sleep study in children with ADHD, LDX did not appear to contribute to any sleep disturbances as measured by both objective and subjective sleep parameters. The sample used in this study was small, and the multifarious nature of findings in this study warranted that the study conclusions be interpreted cautiously and that further study is required focusing on the influence of LDX on sleep in larger samples of ADHD children.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Polysomnography; Sleep; Treatment Outcome

To search for predictors of placebo response in clinical trials of lisdexamfetamine dimesylate for the treatment of DSM-IV-TR-defined attention-deficit/hyperactivity disorder (ADHD) in children and adults.. We used data from 2 clinical trials: (1) a 4-week, phase 3, multicenter, randomized, double-blind, forced-dose, parallel-group study of children aged 6 to 12 years with ADHD (n = 290) and (2) a 4-week, randomized, double-blind, placebo-controlled, parallel-group, forced-dose titration study in adult subjects, aged 18-55 years with ADHD (n = 420). Response and remission were defined using the ADHD Rating Scale-IV and the Clinical Global Impressions-Improvement scale.. Symptom remission was inversely correlated with baseline severity in both children and adults (P < .001), with less robust effects seen for response. The time to response and remission was delayed in adult subjects prescribed placebo versus lisdexamfetamine dimesylate, while response time in children was also significantly slower with placebo versus lisdexamfetamine dimesylate (P < .01). We found little evidence that demographic factors, prior pharmacotherapy, the emergence of adverse events during the trial, or changes in ADHD symptoms from the screening to baseline assessments predicted placebo response. Certain comorbid medical symptoms reduced the response and remission rates to placebo in children (P < .001) and adults (P < .001).. In both children and adults, baseline symptom severity was the most consistent predictor of remission with placebo while the temporal profile of response reliably differentiated placebo from medication responders. Placebo effects are most likely to be minimized in shorter trials enrolling more severely impaired subjects. The impact of medical and psychiatric comorbidities on placebo response merits further investigation.. clinicaltrials.gov identifiers NCT00556296 and NCT00334880.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Comorbidity; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Forecasting; Humans; Lisdexamfetamine Dimesylate; Middle Aged; Placebos; Severity of Illness Index; Treatment Outcome; Young Adult

To examine lisdexamfetamine dimesylate (LDX) efficacy and safety versus placebo in adolescents with attention-deficit/hyperactivity disorder (ADHD).. Adolescents (13 through 17) with at least moderately symptomatic ADHD (ADHD Rating Scale IV: Clinician Version [ADHD-RS-IV] score ≥28) were randomized to placebo or LDX (30, 50, or 70 mg/d) in a 4-week, forced-dose titration, double-blind study. Primary and secondary efficacy measures were the ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), and Youth QOL-Research Version (YQOL-R). Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, laboratory findings, physical examinations, and ECG.. Overall, 314 participants were randomized; 309 were in efficacy analyses and 49 withdrew (11 due to TEAEs). Least squares mean (SE) change from baseline at endpoint in ADHD-RS-IV total scores were -18.3 (1.25), -21.1 (1.28), -20.7 (1.25) for 30, 50, and 70 mg/d LDX, respectively; -12.8 (1.25) for placebo (p ≤ .0056 versus placebo for each). Differences in ADHD-RS-IV total scores favored all LDX doses versus placebo at all weeks (p ≤ .0076). On the CGI-I, 69.1% of participants were rated very much/much improved at endpoint with LDX all doses versus placebo (39.5%) (p < .0001). YQOL-R changes at endpoint scores for LDX groups versus placebo were not significant. Commonly reported LDX (all doses combined) TEAEs (≥5%) were decreased appetite, headache, insomnia, decreased weight, and irritability. Small mean increases in pulse and blood pressure and no clinically meaningful trends in ECG changes were noted with LDX.. LDX at all doses was effective versus placebo in treating adolescent ADHD and demonstrated a safety profile consistent with previous LDX studies. CLINICAL TRIALS REGISTRY INFORMATION: Efficacy and Safety of Lisdexamfetamine Dimesylate (LDX) in Adolescents With Attention-Deficit/Hyperactivity Disorder (ADHD); http://www.clinicaltrials.gov; NCT00735371.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lisdexamfetamine Dimesylate; Male; Personality Assessment; Psychometrics; Quality of Life; Treatment Outcome; United States

To examine the impact of baseline severity on lisdexamfetamine dimesylate (LDX) efficacy in a long-term study of adults with attention-deficit/hyperactivity disorder (ADHD).. Adults from a 4-week, placebo-controlled, forced dose-escalation study with LDX (30-70 mg/day) or placebo were enrolled in a long-term, open-label dose-optimization study for an additional 12 months. In post hoc analyses, participants were stratified by baseline severity (from the prior short-term study) with Clinical Global Impressions-Severity (CGI-S) scores of 4 (moderately), 5 (markedly), or ≥6 (severely/extremely ill). ADHD-Rating Scale IV (ADHD-RS-IV) with adult prompts (primary) and CGI-Improvement (CGI-I) were used to assess effectiveness. Clinical response was defined as a ≥30% decrease in ADHD-RS-IV from baseline and a CGI-I of 1 or 2; symptomatic remission was defined as ADHD-RS-IV ≤18. Treatment-emergent adverse events (TEAEs) were monitored.. Participants had baseline CGI-S scores of 4 (n = 114), 5 (n = 188), or ≥6 (n = 43). At endpoint, mean (SD) change from baseline in ADHD-RS-IV was greater (p < 0.0001) for participants with CGI-S = 5 (-26.4 [11.77]) and ≥6 (-32.3 [9.81]) than for participants with CGI-S = 4 (-19.5 [9.97]). At endpoint, 81.6%, 84.6%, and 88.4% of participants were very much/much improved (CGI-I of 1 or 2) in CGI-S categories of 4, 5, and ≥6, respectively. Clinical response criteria were met by 78.9%, 83.5%, and 88.4% and symptomatic remission criteria by 64.0%, 65.4%, and 72.1% of participants with CGI-S = 4, 5, and ≥6, respectively. The most frequently reported TEAEs with participant incidence ≥10% for any LDX dose were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%).. Some aspects of these analyses (e.g., open-label design without placebo control, inclusion and exclusion criteria of the demographic profile of participants, and the post hoc nature of the statistical analysis) limit interpretation. However, long-term LDX treatment demonstrated increased degree of symptom improvement with greater baseline symptom severity. Rates of clinical response and symptomatic remission tended to be greater for those with greater baseline severity. LDX demonstrated a safety profile consistent with long-acting stimulant use.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Young Adult

To examine duration of efficacy of lisdexamfetamine dimesylate (LDX) in adults with attention-deficit/hyperactivity disorder (ADHD) by effect size in performance and symptom improvement in a simulated adult workplace environment (AWE).. Adults (aged 18-55 years) with ADHD enrolled in the AWE study of LDX with open-label dose-optimization and randomized, placebo-controlled, double-blind, 2-way crossover phases. Efficacy measures included the Permanent Product Measure of Performance (PERMP)-Attempted (-A) and PERMP-Correct (-C) scores assessed throughout the day and the ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts. Model-based least-squares (LS) mean effect size was assessed for PERMP and post-hoc ADHD-RS-IV with adult prompts. Remission was defined as an ADHD-RS-IV total scores ≤ 18. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.. Least-squares mean (standard error [SE]) effect sizes were 0.9 (0.17) for PERMP-A and 0.8 (0.16) for PERMP-C for all postdose sessions. For PERMP-A, postdose LS mean (SE) effect sizes were 0.5 (0.15), 0.8 (0.16), 0.7 (0.16), 0.7 (0.16), 0.7 (0.16), and 0.6 (0.16) at 2, 4, 8, 10, 12, and 14 hours, respectively. Medium-to-large effect sizes (0.5-0.8) were generally maintained from 2 to 14 hours for all PERMP assessments. Overall LS mean (SE) ADHD-RS-IV total and subscale effect sizes were -1.2 (0.19), -1.2 (0.19), and -1.0 (0.17), respectively. Remission was achieved in 67.6% of participants receiving LDX. Treatment-emergent adverse events (≥ 5% with LDX) during the 4-week dose-optimization phase were decreased appetite, dry mouth, headache, insomnia, upper respiratory tract infection, irritability, nausea, anxiety, and feeling jittery. During the crossover week on LDX, there were no TEAEs ≥ 5%.. In adults studied in the AWE, medium-to-large model-based effect sizes were maintained from 2 to 14 hours postdose, on a performance-based measure of productivity, suggesting participants experienced improvement in sustained attention throughout the day and into the evening hours. Lisdexamfetamine dimesylate demonstrated a safety profile consistent with long-acting stimulants.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Neuropsychological Tests; Remission Induction; Severity of Illness Index; Treatment Outcome; Young Adult

This article introduces a ?younger at-risk sibling? design to study progression from other psychopathologies to their substance use disorder (SUD) complications. The design selects not-yet-SUD adolescents with high-risk-for-SUD psychopathology only if an older sibling has SUD. This "proof of concept' pilot study examines the design?s feasibility if the younger sibling has attention deficit hyperactivity disorder (ADHD).. Subjects were recruited from families at substance abuse treatment centers that had a non-SUD younger child with ADHD, from families at behavior disorder clinics that had a younger child with ADHD and SUD older child, and through general advertisements. Subjects were seen weekly for at least 3 months and monthly thereafter for 3 months. All were treated with open-label lisdexamfetamine dimesylate 30-70 mg per day. Outcomes explored were recruitment, compliance, diversion, ADHD improvement, and substance use interest.. 25 families were screened, 13 evaluated, and 8 began medication. ADHD Rating Scale-IV scores obtained by parent?adolescent consensus improved as expected with a stimulant. Rating forms could quantify substance use interest in subjects with some drug culture exposure but encountered a floor effect in those without. The design's complexity and implicit commentary on family dynamics complicated recruitment but may have facilitated retention.. Sibling pairs in which the older sibling has substance use and the younger sibling has ADHD exist. Such younger siblings can be recruited into a treatment study. The design may shed light on the pathogenesis and prevention of SUD complications from ADHD and theoretically other SUD comorbidities.

Topics: Adolescent; Adolescent Behavior; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Diagnosis, Dual (Psychiatry); Female; Humans; Lisdexamfetamine Dimesylate; Male; Medication Adherence; Pilot Projects; Research Design; Risk Factors; Siblings; Substance-Related Disorders

To assess improvements in quality of life measurements during the open-label portion of a trial examining duration of efficacy of lisdexamfetamine dimesylate in a simulated adult workplace environment.. A 4-week, open-label, dose-optimization phase followed by a randomized, double-blind, multicenter, placebo-controlled, 2-way crossover phase to evaluate safety and efficacy of lisdexamfetamine dimesylate in the adult workplace environment was conducted. Clinical assessments included the ADHD Impact Module for Adults (AIM-A) to assess the effect of lisdexamfetamine dimesylate on perception of quality of life and the Clinical Global Impressions-Severity/Improvement to assess symptom severity at baseline and improvement over time. Safety assessments included physical examination, treatment-emergent adverse events, vital signs, and electrocardiogram measurements.. Questions 1 and 4 of the AIM-A suggest improvement from baseline in overall quality of life at week 4 with lisdexamfetamine dimesylate treatment. Post-hoc analysis revealed no significant differences attributable to either age or sex. Overall responses to questions 2 and 3, which related to overall life goals, did not change in a majority of participants during the 4-week open-label phase of this study. For all lisdexamfetamine dimesylate doses combined, treatment-emergent adverse events occurring in ≥ 5% of participants during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%).. At the end of the dose-optimization phase, lisdexamfetamine dimesylate treatment suggested quality of life improvements in adults with ADHD, with a safety profile consistent with long-acting stimulant use.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Quality of Life; Self Report; Workplace; Young Adult

Sleep disturbances may cause distress among individuals with attention-deficit/hyperactivity disorder (ADHD), but few studies have examined the impact of stimulant pharmacotherapy for ADHD on sleep in adults.. These post hoc analyses included sleep data collected with the Pittsburgh Sleep Quality Index (PSQI), a self-rated questionnaire, from 831 adults with DSM-IV-TR-defined ADHD in 2 large, randomized, double-blind, placebo-controlled, forced-dose titration studies of lisdexamfetamine (N = 420; conducted from May 25, 2006, to November 16, 2006) and triple-bead mixed amphetamine salts (MAS) (N = 411; conducted from April 25, 2005, to November 4, 2005). Change from baseline to endpoint in PSQI clinically meaningful change categories (ie, "decrease," "no change," or "increase") was analyzed by treatment group in each study using the χ² test. The Cochran-Mantel-Haenszel method was used (1) to determine whether there was a statistically significant difference in Clinical Global Impressions-Improvement (CGI-I) score of 1 or 2 (improved) versus > 2 (not improved) relative to a decrease or an increase in PSQI and (2) to analyze shifts from good sleep at baseline (PSQI ≤ 5) to poor sleep at endpoint (PSQI > 5).. Impaired sleep (PSQI score > 5) relative to baseline was demonstrated in 8.3% and 9.7% of the treatment and placebo groups, respectively (P = .18), in the MAS study and 7.7% and 8.2%, respectively (P = .03), in the lisdexamfetamine study. Clinically meaningful change in baseline to endpoint PSQI was not statistically significantly different between treatment and placebo groups in either study. A significant difference in CGI-I 1 and 2 relative to an increase or decrease in PSQI was found in both the triple-bead MAS (P < .0001) and the lisdexamfetamine (P = .0008) trials. More subjects with improved CGI-I rating of 1 or 2 had improvement in PSQI than had worsening.. Approximately one-third of subjects receiving treatment or placebo had clinically meaningful sleep improvement, emphasizing that change in sleep quality during treatment may not necessarily be related to stimulant therapy. When managing complaints of sleep difficulties in ADHD subjects, clinicians should undertake a broad assessment and consider underlying conditions that may contribute to sleep disruption.. clinicaltrials.gov Identifiers: NCT00334880 and NCT00152022.

Topics: Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Sleep; Sleep Initiation and Maintenance Disorders; Surveys and Questionnaires

This analysis assessed the relationship of various cutoff scores of the ADHD Rating Scale IV (ADHD-RS-IV) to levels of improvement in ADHD-related executive function (EF), measured by the Brown ADD Scale for Adults (BADDS), which may provide a measure of clinically meaningful EF improvement after ADHD treatment.. Post hoc analysis of a 4-week, open-label, dose-optimization phase in a double-blind, placebo-controlled study of lisdexamfetamine dimesylate (LDX) in adults with ADHD. The BADDS for Adults, a validated, normed, self-report measure of EF in ADHD, provides a qualitative measure to rate treatment progress. The ADHD-RS-IV assesses current symptom status based on DSM-IV criteria. Postbaseline ADHD-RS-IV scores were categorized according to four cutoff criteria of symptom remission: (1) ADHD-RS-IV total score ≤ 18; (2) ADHD-RS-IV total score ≤ 10; (3) no ADHD-RS-IV item scored >1; and (4) ADHD-RS-IV total score ≤ 18 and ≤ 2 items per subscale with a score of 2. Sensitivity and specificity of criteria for identifying participants with optimal BADDS scores were assessed using receiver operating characteristics (ROC). Safety evaluation included treatment-emergent adverse events (TEAEs).. At endpoint, 85/127 participants had optimal BADDS scores. Linear ANOVA indicated limited overlap between BADDS and ADHD-RS-IV scores (r (2) = 0.20; P < 0.0001). Specificity was similar for criteria 1-4 (0.46, 0.39, 0.39, and 0.42), as were ROC (0.699, 0.776, 0.732, and 0.668). Sensitivity was high for criteria 2 and 3 (0.96, 0.92), lower for criteria 1 and 4 (0.72, 0.75). TEAEs were consistent with those of stimulants.. Criteria 2 and 3 had satisfactorily high sensitivity, but no criteria had adequate specificity. AUC comparison indicated that criteria 2 and 3 ADHD-RS-IV thresholds may be more accurate assessments of EF normalization as measured by the BADDS. The open-label design, small sample size, and selection criteria limit the applicability of these results to a larger treatment population.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Psychiatric Status Rating Scales; ROC Curve; Young Adult

The pharmacokinetics of lisdexamfetamine dimesylate, a long-acting prodrug stimulant, and its active moiety, d-amphetamine, including dose-proportionality and variability, were assessed in 20 healthy adults. Subjects received a single dose, sequentially, of 50, 100, 150, 200, and 250 mg of lisdexamfetamine dimesylate. Plasma lisdexamfetamine dimesylate and d-amphetamine were measured before dosing and 0.25 to 96 hours postdose. Dose-proportionality and intersubject and intrasubject variability of pharmacokinetic parameters were examined. Safety assessments included adverse events. All 20 subjects received 50 and 100 mg while 18, 12, and 9 subjects received 150, 200, and 250 mg of lisdexamfetamine dimesylate, respectively. Ten subjects were discontinued during the study for prespecified stopping rules (2 consecutive hourly readings of blood pressure: systolic >160 mm Hg or diastolic >100 mm Hg). Mean maximum observed plasma concentration (C(max)) and area under the concentration-time curve from time 0 to infinity (AUC(0-∞)) increased linearly and dose-dependently for d-amphetamine. Median time to C(max) ranged from 4 to 6 hours for d-amphetamine and 1.0 to 1.5 hours for lisdexamfetamine dimesylate. Intersubject and intrasubject variability over doses from 50 to 150 mg was low (<20%) for both C(max) and AUC(0-∞). Adverse events included nausea, dizziness, headache, psychomotor hyperactivity, and dysuria. These findings indicate that the pharmacokinetic parameters of d-amphetamine were dose-proportional and predictable over a wide range of lisdexamfetamine dimesylate doses.

Topics: Adult; Area Under Curve; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Electrocardiography; Female; Headache; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Prodrugs; Pulse; Young Adult

Lisdexamfetamine dimesylate (LDX) is a long-acting oral prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children 6 to 12 years old and in adults. Information on the pharmacokinetic profile of LDX in children with ADHD is lacking.. The aim of this study was to assess the pharmacokinetic properties of d-amphetamine delivery from LDX, and intact LDX with increasing doses of LDX administered in children with ADHD.. This single-dose, randomized, open-label, 3-period crossover study was conducted in children aged 6 to 12 years with ADHD symptoms that adversely affected school performance and required a medication switch. Eligible patients had prior stimulant experience, with good tolerability. Patients were administered a single oral dose of LDX 30, 50, or 70 mg in a randomized sequence. Each study period was separated by a 6-day washout. The pharmacokinetic properties of d-amphetamine and intact LDX were calculated over 48 hours. Adverse events (AEs) were assessed using physical examination, including vital sign measurements, and ECG.. The study enrolled 18 children (mean [SD] age, 9.6 [1.9] years [range, 6-12 years]; 56% boys; weight, 36.0 [7.6] kg; 44% white, 44% black). Mean (%CV) C(max) values of d-amphetamine postdose were 53.2 (18.1), 93.3 (19.5), and 134.0 (19.4) ng/mL with LDX 30, 50, and 70 mg, respectively (T(max), approximately 3.5 hours). These findings suggest that the overall AUC for d-amphetamine was dose proportional. The intact LDX AUC was 10% to 20% higher in girls than in boys, and for d-amphetamine was <10% higher. The most commonly reported AEs, of 17 total cases, with 30-, 50-, and 70-mg LDX were anorexia (4 [22%], 7 [41%], and 8 [47%], respectively), elevated blood pressure (2 [11%], 1 [6%], and 3 [18%]), and abdominal pain (2 [11%], 2 [12%], and 2 [12%]). All AEs were mild or moderate. No serious AEs were reported. One child was withdrawn from the analysis because of pharyngitis considered to be unrelated to LDX use.. The findings from this study in a small, select population of children with ADHD suggest that the concentrations of d-amphetamine, the active metabolite of LDX, after single-dose administration of LDX at increasing doses appeared to be dose proportional and had low interpatient variability.

Topics: Administration, Oral; Attention Deficit Disorder with Hyperactivity; Biotransformation; Central Nervous System Stimulants; Child; Cross-Over Studies; Dextroamphetamine; Dose-Response Relationship, Drug; Female; Humans; Lisdexamfetamine Dimesylate; Male; Prodrugs; Treatment Outcome

Duration of efficacy and safety of lisdexamfetamine dimesylate (LDX) was assessed in adults (18-55 years) with attention-deficit/hyperactivity disorder (ADHD) using the simulated adult workplace environment.. After open-label dose optimization (4-week) with LDX, 30-70 mg/d, subjects entered a 2-week randomized, double-blind, placebo-controlled crossover phase. Efficacy assessments included the Permanent Product Measure of Performance (PERMP) total score (attempted+correct) measured predose and from 2 to 14 hours postdose, averaged across postdose sessions (primary) and at each time point vs placebo (secondary), and ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts at baseline and crossover visits. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms.. Of 127 randomized subjects, 105 were in the intention-to-treat population and 103 completed the study. While receiving LDX vs placebo, adults had greater improvement (P < .0001) in average PERMP total scores as measured by difference in least squares (LS) mean (95% CI): 23.4 (15.6, 31.2). Absolute (P or=10%) during dose optimization were decreased appetite, dry mouth, headache, and insomnia; no TEAEs >or=5% were reported during crossover phase for adults receiving LDX.. LDX significantly improved PERMP scores vs placebo and maintained improvement throughout the day from the first (2 hours) to last (14 hours) postdose time point vs placebo in adults with ADHD.. ClinicalTrials.gov Identifier: NCT00697515. Safety and Efficacy Workplace Environment Study of Lisdexamfetamine Dimesylate (LDX) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD) http://www.clinicaltrials.gov/ct2/show/NCT00697515?term=NCT00697515&rank=1.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Cross-Over Studies; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Psychiatric Status Rating Scales; Psychotropic Drugs; Time Factors; Treatment Outcome; Work; Young Adult

Executive function (EF) impairment in attention-deficit/hyperactivity disorder (ADHD) may account for behavioral symptoms such as poor concentration, impaired working memory, problems in shifting among tasks, and prioritizing and planning complex sets of tasks or completing long-term projects at work or school. Poor self-regulation and control of emotional behaviors frequently are seen in patients with ADHD. This study assessed EF behaviors in adults with ADHD at baseline and after 4 weeks of treatment with lisdexamfetamine dimesylate (LDX).. Executive function behavior was assessed using the Brown Attention-Deficit Disorder Scale (BADDS) during the 4-week open-label dose-optimization phase prior to a 2-period, randomized, double-blind, placebo-controlled crossover study of LDX (30-70 mg/day). The ADHD Rating Scale IV (ADHD-RS-IV) with adult prompts assessed ADHD symptoms. Change in EF behavioral symptoms was evaluated based on week 4 BADDS total and cluster scores; analyses of shifts from baseline among subjects with BADDS scores < 50, 50 to 59, 60 to 69, and ≥ 70; and scores less than or greater than baseline 90% confidence range (eg, reliably improved or worsened, respectively). Treatment-emergent adverse events (TEAEs) were described.. At week 4, BADDS total and cluster scores were reduced (ie, improved; all P < 0.0001 vs baseline [n = 127]). The ADHD-RS-IV with adult prompts scores also improved (all P < 0.0001 vs baseline). At week 4, 62.7% of subjects had a BADDS total score of < 50, and 78.9% were reliably improved; 1.4% were reliably worsened. Common TEAEs (≥ 5%) during the dose-optimization phase were decreased appetite (36.6%), dry mouth (30.3%), headache (19.7%), insomnia (18.3%), upper respiratory tract infection (9.9%), irritability (8.5%), nausea (7.7%), anxiety (5.6%), and feeling jittery (5.6%).. Clinically optimized doses of LDX (30-70 mg/day) significantly improved EF behaviors in adults with ADHD. Treatment-emergent adverse events with LDX were consistent with those observed with long-term stimulant use.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male

To evaluate the safety profile, based on cardiovascular measurements, of lisdexamfetamine dimesylate (LDX) in children with and without prior exposure to stimulant medication in the treatment of attention-deficit/hyperactivity disorder (ADHD).. This single-blind, modified laboratory school study used open-label dose optimization of children aged 6 to 12 years. Lisdexamfetamine dimesylate, initiated at 30 mg, was dose titrated in 20-mg weekly increments to a possible 70 mg over 4 to 5 weeks. Safety outcomes presented in this study were assessed using vital signs (blood pressure and pulse) and electrocardiograms, conducted at baseline and following LDX treatment. Analyses were performed across all subjects, as well as post hoc based on prior treatment status. In addition, hematologic and blood biochemistry analyses were conducted at baseline but not following treatment.. Twenty-eight subjects enrolled in the study, with 27 safety protocol completers (n = 14 prior stimulant exposure; n = 13 stimulant naïve). In total, 2 subjects in the stimulant-naïve group experienced changes from baseline vital sign measurements outside the normal range: 1 with tachycardia and 1 with blood pressure ≥ 95th percentile of the normal age range. One other subject in the stimulant-naïve group experienced prolonged QTc in response to LDX, which resolved at follow-up. Pretreatment laboratory work revealed no differences on any parameters when reviewed by exposure subgroup.. While LDX reduced the core symptoms of ADHD to a similar degree in treatment-naïve and previously treated groups of children with ADHD, more cardiovascular effects were measured in stimulant-naïve children than in children who had previously been exposed to stimulant treatment. Future controlled studies with larger samples should address the impact of prior stimulant exposure on other ADHD treatments.

Topics: Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Lisdexamfetamine Dimesylate; Male; Single-Blind Method; Systole; Tachycardia

To assess the effects of lisdexamfetamine dimesylate (LDX) on executive function (EF) behaviors in children with attention-deficit/hyperactivity disorder (ADHD).. This observational, open-label, 7-week, dose-optimization study of LDX (20-70  mg/day) in children with ADHD evaluated efficacy with the ADHD Rating Scale IV; safety measures included adverse events (AEs). EF was assessed with the Behavior Rating Inventory of Executive Function (BRIEF). Post hoc analyses examined BRIEF scores by sex, ADHD subtype, comorbid psychiatric symptoms, and common treatment-emergent AEs (TEAEs). ADHD Rating Scale IV scores were assessed in subjects categorized by baseline BRIEF global executive composite T scores with clinically significant (≥65) or not clinically significant (<65) impairment in EF.. Mean (standard deviation) change from baseline to endpoint for BRIEF of -17.9 (12.5) for Global Executive Composite, -15.4 (12.6) for Behavioral Regulation Index, and -17.6 (12.3) for Metacognition Index demonstrated improvement with LDX (pooled doses; p < 0.0001 for all). Improvements in BRIEF scores were seen regardless of sex, ADHD subtype, comorbid psychiatric symptoms, common TEAEs, or baseline EF impairment category. TEAEs included decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia.. Improvements were demonstrated in EF behaviors and ADHD symptoms with LDX. LDX safety profile was consistent with long-acting stimulant use.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Neuropsychological Tests; Prospective Studies; Psychometrics

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Central Nervous System Stimulants; Dextroamphetamine; Double-Blind Method; Dyspnea; Female; Headache; Humans; Irritable Mood; Lisdexamfetamine Dimesylate; Male; Middle Aged; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome; Young Adult

The aim of this study was to assess the effectiveness and safety of lisdexamfetamine dimesylate (LDX) in children with attention-deficit/hyperactivity disorder (ADHD).. This was a 7-week, open-label study evaluating 20, 30, 40, 50, 60, or 70 mg/day LDX in 318 children aged 6-12 years with ADHD. The ADHD Rating Scale IV (ADHD-RS-IV) was the primary efficacy assessment. Secondary measures included the Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), and Behavior Rating Inventory of Executive Function (BRIEF). Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, and electrocardiograms.. At end point, mean (standard deviation [SD]) improvement from baseline in ADHD-RS-IV total score was 28.6 (10.9) (p < 0.0001). Most subjects (89.9%) were rated "improved" (i.e., CGI-I 1 or 2). Improvements from baseline were observed in the EESC total and subscale scores (p < or = 0.0002). LDX treatment resulted in significant improvement on the Global Executive Composite, Behavioral Regulation, and Metacognition indices of the BRIEF (p < 0.0001). TEAEs (incidences > or =10%) were decreased appetite, decreased weight, irritability, insomnia, headache, upper abdominal pain, and initial insomnia.. LDX was effective and generally well tolerated with a safety profile consistent with long-acting stimulant use. There was overall improvement in ADHD symptoms and executive function measures and no worsening of emotional expression measures.. clinicaltrials.gov Identifier: NCT00500071.

Topics: Appetite; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Electrocardiography; Executive Function; Expressed Emotion; Female; Humans; Lisdexamfetamine Dimesylate; Male; Patient Satisfaction; Prodrugs; Psychiatric Status Rating Scales; Severity of Illness Index; Treatment Outcome; Weight Loss

To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).. Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.. A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P < .0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P < .0001).. LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Lisdexamfetamine Dimesylate; Longitudinal Studies; Male; Middle Aged; Psychiatric Status Rating Scales; Severity of Illness Index; Time Factors; Vital Signs; Young Adult

To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD).. Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter.. There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P < .05 for lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety population) of subjects had treatment-emergent cardiovascular adverse events, and 1.7% (7/420) withdrew from the study because of cardiovascular complaints. Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically healthy adults were generally mild to moderate in severity.. Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as prescribed.. clinicaltrials.gov Identifier: NCT00334880.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Blood Pressure; Cardiovascular System; Central Nervous System Stimulants; Dextroamphetamine; Electrocardiography; Female; Heart Rate; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Placebos; Prodrugs; Treatment Outcome

Lisdexamfetamine dimesylate (LDX), a prodrug stimulant, is indicated for attention-deficit/hyperactivity disorder (ADHD) in children 6-12 years of age and in adults. In short-term studies, once-daily LDX provided efficacy throughout the day. This study presented here was conducted to assess the long-term safety, tolerability, and effectiveness of LDX in 6- to 12-year-olds with ADHD.. This open-label, multicenter, single-arm study enrolled children with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Text Revision criteria for ADHD. Following 1-week screening and washout periods, subjects were titrated to LDX 30, 50, or 70 mg/day over 4 weeks and placed on maintenance treatment for 11 months. The ADHD Rating Scale and Clinical Global Impression-Improvement scale measured effectiveness.. Of 272 subjects receiving LDX, 147 completed the study. Most adverse events were mild to moderate and occurred during the first 4 weeks. There were no clinically meaningful changes in blood pressure or electrocardiographic parameters. From baseline to endpoint, mean ADHD Rating Scale scores improved by 27.2 points (P<.0001). Improvements occurred during each of the first 4 weeks, and were maintained throughout. Based on Clinical Global Impression-Improvement scale scores, >80% of subjects at endpoint and >95% of completers at 12 months were rated "improved.". Long-term 30, 50, and 70 mg/day LDX was generally well tolerated and effective in children with ADHD.

Topics: Administration, Oral; Appetite; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Headache; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome; Weight Loss

To evaluate the efficacy of lisdexamfetamine dimesylate (LDX) in school-aged children with attention-deficit/hyperactivity disorder (ADHD), using the Conners' Parent Rating Scale, Revised Short Version (CPRS-R:S) and its subscales.. This was a secondary post hoc analysis of data from a placebo-controlled, double-blind, parallel-group, forced dose-escalation trial. Boys and girls aged 6 to 12 years with a primary diagnosis of ADHD were randomly assigned to LDX (30, 50, or 70 mg/d) or placebo. Improvement on the CPRS-R:S and its subscales (ADHD Index, hyperactivity, oppositional, and cognition) at 10:00 AM, 2:00 PM, and 6:00 PM was analyzed. Safety assessments included the identification of adverse events and were conducted throughout the study.. Of the 290 patients randomized, 285 were included in the intent-to-treat population. Parents noted significant improvements at all 3 assessment times on the CPRS-R:S total score and for the CPRS-R:S ADHD Index, hyperactivity, and cognition subscales, regardless of the subject baseline disease severity. For the CPRS-R:S oppositional subscale, significant improvement was noted at 10:00 AM and 2:00 PM (P < 0.01), and overall, significant improvement occurred in subjects who were more severely ill at baseline. The tolerability of LDX was comparable to that of other stimulants.. Once-daily treatment with LDX was associated with significant improvement in parent-rated assessments of ADHD-related behavior throughout the day at approximately 10:00 AM, 2:00 PM, and 6:00 PM. Lisdexamfetamine dimesylate was effective and well tolerated in this study population of children aged 6 to 12 years with ADHD.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Double-Blind Method; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Male; Parents; Psychological Tests; Social Behavior; Treatment Outcome

To evaluate the efficacy and safety of 30, 50, and 70 mg/day lisdexamfetamine dimesylate compared with placebo in adults with attention-deficit/hyperactivity disorder (ADHD).. Following a 7- to 28-day washout, 420 adults aged 18 to 55 years with moderate to severe ADHD (DSM-IV-TR criteria) were treated with 30, 50, or 70 mg/day lisdexamfetamine or placebo, respectively, for 4 weeks (N = 119, 117, 122, and 62, respectively). The 50- and 70- mg/day groups underwent forced-dose titration. The primary efficacy measure was the clinician-determined ADHD Rating Scale (ADHD-RS) total score. The study was conducted from May 2006 to November 2006.. Treatment groups were well matched at baseline, including in ADHD-RS scores. At endpoint, changes in ADHD-RS scores were significantly greater for each lisdexamfetamine dose than for placebo (placebo = -8.2, 30 mg/day lisdexamfetamine = -16.2, 50 mg/day lisdexamfetamine = -17.4, 70 mg/day lisdexamfetamine = -18.6; all p < .0001 vs. placebo), with no differences between doses. Significant differences relative to placebo were observed in each lisdexamfetamine group, beginning at week 1 and for each week throughout. The percentage of subjects who improved (Clinical Global Impressions-Improvement scale rating < or = 2) was significantly greater for each lisdexamfetamine dose than for placebo at each week and at endpoint (placebo = 29%, 30 mg/day lisdexamfetamine = 57%, 50 mg/day lisdexamfetamine = 62%, 70 mg/day lisdexamfetamine = 61%; all p < .01). Adverse events were generally mild and included dry mouth, decreased appetite, and insomnia.. All 3 lisdexamfetamine doses were significantly more effective than placebo in the treatment of adults with ADHD, with improvements noted within 1 week. Lisdexamfetamine was generally well tolerated by these patients.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Personality Assessment; Young Adult

Lisdexamfetamme dimesylate (LDX) is a therapeutically inactive amphetamine prodrug. It was developed with the goal of providing an extended duration of effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Following ingestion, the pharmacologically active d-amphetamine molecule is gradually released by rate-limited hydrolysis.. The aims of this study were to assess the efficacy and tolerability of LDX in school-aged children with attention-deficit/hyperactivity disorder (ADHD) treated in the community, and to characterize the duration of action of LDX compared with placebo.. This Phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study was conducted at 40 centers across the United States. Male and female children aged 6 to 12 years with ADHD were randomly assigned to receive LDX 30, 50, or 70 mg with forced-dose titration, or placebo, PO QD for 4 weeks. Efficacy was assessed using the ADHD Rating Scale Version IV (ADHD-RS-IV), the Conners' Parent Rating Scale (CPR'), and the Clinical Global Impression of Improvement scale. Tolerability was assessed throughout the study.. Of the 290 randomized patients (201 boys, 89 girls; mean [SD] age, 9 [1.8] years), 230 completed the trial (LDX 30 mg, n=56; LDX 50 mg, n=60; LDX 70 mg, n=60; and placebo, n=54). The most common reasons for study discontinuation (n=60) were lack of efficacy (LDX 30 mg, 1%; LDX 50 mg, 0%; LDX 70 mg, 1 %; and placebo, 17%) and adverse events (AEs) (LDX 30 mg, 9%; LDX 50 mg, 5%; LDX 70 mg, 14%; and placebo, 1%). Significant improvements in ADHD-RS-IV scores were seen with all doses of LDX compared with placebo (all, P<0.001), and in CPRS scores with all LDX doses versus placebo throughout the day (all, P<0.001 for all comparisons). Efficacy was observed by the first week of treatment, and improvements were observed throughout the day up to approximately 6 PM. The most frequently reported AEs among patients receiving LDX were typical of amphetamine products: decreased appetite (39% with active treatment vs 4% with placebo), insomnia (19% vs 3%), upper abdominal pain (12% vs 6%), headache (12% vs 10%), irritability (10% vs 0%), vomiting (9% vs 4%), weight decrease (9% vs 1%), and nausea (6% vs 3%); most were mild to moderate and occurred in the first week.. In this population of children with ADHD, treatment once daily with the prodrug LDX at doses of 30 to 70 mg appeared to be effective and had a tolerability profile similar to those of currently marketed extended-release stimulants.

Topics: Administration, Oral; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dextroamphetamine; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Lysine; Male; Treatment Outcome

Lisdexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine, a naturally occurring amino acid. Pharmacologically active d-amphetamine is released from lisdexamfetamine following oral ingestion.. This phase 2, randomized, double-blind, placebo- and active-controlled crossover study compared the efficacy and safety of lisdexamfetamine (LDX: 30, 50, or 70 mg) with placebo, with mixed amphetamine salts extended-release (MAS XR: 10, 20, or 30 mg) included as a reference arm of the study, in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD) in an analog classroom setting. The primary efficacy measure was the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale; secondary efficacy measures included the Permanent Product Measure of Performance (PERMP) Derived Measures, and the Clinical Global Impression (CGI) Scale.. LDX treatment significantly improved scores on SKAMP-deportment, SKAMP-attention, PERMP-attempted, PERMP-correct, and CGI-improvement from baseline. Adverse events were similar for both active treatments.. In a laboratory classroom environment, LDX significantly improved ADHD symptoms versus placebo in school-age children with ADHD.

Topics: Amphetamine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Over Studies; Delayed-Action Preparations; Dextroamphetamine; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Psychiatric Status Rating Scales; Time Factors; Treatment Outcome

This study aimed to describe recent trends in ADHD medication use in pregnancy in Norway and Sweden, including prevalence, individual characteristics, and patterns of use.. We studied ADHD medication use (amphetamine, dexamphetamine, methylphenidate, atomoxetine, lisdexamfetamine, guanfacine) by year and age in pregnancies from 2010 to 2019 identified from the medical birth registers (gestational age ≥ 22 weeks) linked to prescribed drug registers (Norway, N = 577,116; Sweden, N = 1,118,988). We compared characteristics of those who used any ADHD medication in pregnancy to no use in pregnancy. Discontinuation was defined as no use after first trimester.. ADHD medication use increased from 2010 to 2019 by 3.0 users per 1000 pregnancies in Norway (from 2.5 to 5.5/1000) and by 6.3 per 1000 in Sweden (from 1.6 to 7.9/1000), mainly driven by methylphenidate and since 2015 by lisdexamfetamine. Medication use has increased among pregnant individuals of all age groups, with higher use among the youngest. Pregnant individuals who used ADHD medication were less likely to be married/cohabiting, more likely be nulliparous and to smoke. They had particularly high use of co-medication with antidepressants, anxiolytics/hypnotics, and opioids: 42% in Norway and 65% in Sweden used at least one additional class of psychotropic medication. Most individuals discontinued ADHD medication in pregnancy (85% Norway, 78% Sweden).. ADHD medication use during pregnancy increased in Norway and Sweden in the last decade. However, discontinuation rates during pregnancy were high. Those who used ADHD medication had more risk factors for pregnancy complications including low parity, smoking, and other psychotropic drug use.

Topics: Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Female; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Norway; Pregnancy; Prevalence; Sweden

Although the study of cognitive disengagement syndrome (CDS; previously called sluggish cognitive tempo) first emerged in the 1980s, very little is known about treating CDS or its impact on evidence-based interventions for attention-deficit/hyperactivity disorder (ADHD) with which it frequently co-occurs. The objective of this leading article was to investigate the existing evidence on medication treatment and CDS, including studies that have examined CDS response to medication and CDS as a moderator of ADHD treatment response. A total of seven studies were identified. At present, the limited existing literature suggests that psychostimulants such as methylphenidate and lisdexamfetamine, as well as atomoxetine, may improve CDS symptoms, although replication and research on related medications is needed. However, there are indications that CDS symptoms may predict a reduced response to methylphenidate in children with ADHD. Although untested, research on the neurobiological, neuropsychological, and behavioral correlates of CDS point to a possible benefit of other ADHD medications (e.g., guanfacine), medications that treat narcolepsy (e.g., modafinil), and medications traditionally used to treat depression and anxiety (e.g., viloxazine, bupropion, fluvoxamine), some of which have also recently been used in ADHD management. The article concludes with recommendations for future research on pharmacologic treatment and CDS.

Topics: Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cognition; Humans; Lisdexamfetamine Dimesylate; Methylphenidate

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

To evaluate the real-world efficacy, safety, and functional outcomes of PRC-063 (multilayer-release methylphenidate) versus lisdexamfetamine (LDX) in ADHD subjects in a phase IV, open-label study.. The primary endpoint was the change in the ADHD-DSM-5 Rating Scale (ADHD-5-RS) total score from baseline to Month 4. Secondary endpoints included a non-inferiority comparison between PRC-063 and LDX and measures of functioning and evening behavior.. One hundred forty-three pediatric and 112 adult subjects were enrolled. Mean ADHD-5-RS scores (standard deviation) were reduced in pediatric (-16.6 [10.4]) and adult (-14.8 [10.6]) subjects treated with PRC-063 (. PRC-063 and LDX significantly improved ADHD symptomatology and functioning and were well-tolerated.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Quality of Life; Treatment Outcome

Treatment of narcolepsy is based on the need to regulate life rhythms. Psychostimulants such as modafinil, methylphenidate-immediate release, and pemoline are used to treat hypersomnia. A psychosocial approach is considered the mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD), and medication is used to treat moderate or severe ADHD symptoms. Two of the four drugs approved in Japan for ADHD therapy (osmotic-release oral system methylphenidate and lisdexamfetamine dimesylate) are psychostimulants, which are administered via the ADHD proper distribution management system.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil

To evaluate treatment patterns for ADHD in Sweden.. Observational retrospective study of patients with ADHD from the Swedish National Patient Register and Prescribed Drug Register, 2018 to 2021. Cross-sectional analyses included incidence, prevalence, and psychiatric comorbidities. Longitudinal analyses (newly diagnosed patients) included medication, treatment lines, duration, time-to-treatment initiation, and switching.. Of 243,790 patients, 84.5% received an ADHD medication. Psychiatric comorbidities were common, particularly autism among children, and depression in adults. Most frequent first-/second-line treatments were methylphenidate (MPH; 81.6%) and lisdexamfetamine dimesylate (LDX; 46.0%), respectively. In the second-line, LDX was most frequently prescribed (46.0%), followed by MPH (34.9%), then atomoxetine (7.7%). Median treatment duration was longest for LDX (10.4 months), followed by amphetamine (9.1 months).. This nationwide registry study provides real-life insights into the current epidemiology of ADHD and the changing treatment landscape for patients in Sweden.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cross-Sectional Studies; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Registries; Retrospective Studies; Sweden; Treatment Outcome

Topics: Amphetamines; Attention Deficit Disorder with Hyperactivity; Catecholamines; Central Nervous System Stimulants; Female; Humans; Lisdexamfetamine Dimesylate; Male; Motivation

Therapeutic drug monitoring (TDM) is a valid tool for the optimization of psychopharmacotherapy; however, in child and adolescent psychiatry, uncomfortable intravenous sample collection is the main challenge and restricts the use of TDM. Therefore, it is important to evaluate alternate specimens to facilitate TDM. The aim of this study was to evaluate the feasibility of using saliva for the TDM of amphetamine in children and adolescents with attention-deficit/hyperactivity disorder.. In this study, 28 patient samples (mean age, 11.3 years; boys, 23; and girls, 5) treated with lisdexamfetamine were included. The active compound amphetamine was extracted and derivatized before quantification by high-performance liquid chromatography with fluorescence detection. Nonparametric Spearman rank correlations were used for correlation analyses; for clinical validation, Bland-Altman analysis was applied.. The median amphetamine concentrations in saliva were 2.7 times higher (range 0.7-23.6) than those in serum (257.8 ng/mL versus 77.2 ng/mL; z = -4.51, P < 0.001). A strong positive linear correlation was observed between saliva and serum concentrations (ρ = 0.628, P < 0.001). The ratio of saliva-to-serum concentration was strongly pH dependent (ρ = -0.712, P < 0.001). Therefore, a transformation formula, factoring in salivary pH, to calculate serum concentrations from the measured saliva concentrations was applied. Theoretical and measured serum amphetamine concentrations were subjected to Bland-Altman analysis. Using an acceptance limit of 20%, only 21% (n = 6) of samples fulfilled this criterion.. Amphetamine paired saliva-to-serum concentrations were highly variable and strongly affected by salivary pH, indicating that saliva is an inappropriate sampling matrix for TDM of amphetamine. Furthermore, Bland-Altman analysis did not support saliva as a suitable matrix for TDM.

Topics: Adolescent; Amphetamine; Attention Deficit Disorder with Hyperactivity; Child; Drug Monitoring; Female; Humans; Lisdexamfetamine Dimesylate; Male; Saliva; Serum

This study examined the feasibility, safety, and potential efficacy of lisdexamfetamine (LDX) as a treatment for adults with bulimia nervosa (BN).. An open-label 8-week feasibility study was conducted in participants with BN. Enrollment rate, dropout rate, safety outcomes, and eating disorder symptom change were examined.. Eighteen of 23 participants completed the study per protocol. There was no participant-initiated dropout due to adverse drug reactions and no severe and unexpected adverse drug reactions. An average increase in heart rate of 12.1 beats/min was observed. There was a mean weight reduction of 2.1 kg and one participant was withdrawn for clinically significant weight loss. In the intent-to-treat sample, there were reductions in objective binge episodes and compensatory behaviors from Baseline to Post/End-of-Treatment (mean difference = -29.83, 95% confidence interval: -43.38 to -16.27; and mean difference = -33.78, 95% confidence interval: -48.74 to -18.82, respectively).. Results of this study indicate that a randomized controlled trial would be feasible with close monitoring of certain safety parameters (especially over a longer time period as long-term safety is unknown). However, the results should not be used as evidence for clinicians to prescribe LDX to individuals with BN before its efficacy and safety are properly tested.. NCT03397446.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Binge-Eating Disorder; Bulimia Nervosa; Central Nervous System Stimulants; Double-Blind Method; Feasibility Studies; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

Topics: Anticonvulsants; Attention Deficit Disorder with Hyperactivity; Catatonia; Central Nervous System Stimulants; Child; Humans; Lisdexamfetamine Dimesylate; Lorazepam; Male

Considering the high clinical and forensic relevance of pharmaco-adherence during lisdexamphetamine (LDX) treatment for attention-deficit/hyperactivity disorder (ADHD), the aim here was to evaluate hair analysis as a tool for monitoring compliance in patients currently undergoing long term treatment with LDX, by detecting possible interruptions of medication intake or changes in dosage. For this purpose, a total of 24 patients from an outpatient clinic for ADHD were recruited. Hair and urine samples were taken after three consecutive therapy sessions over a 7-month period and analyzed for amphetamine (AMP) enantiomers and other drugs, using chiral and achiral liquid chromatography-tandem mass spectrometry (LC-MS/MS). Participants also provided information on the condition of their hair, the consumption of illegal psychotropic substances and the regularity of taking LDX. Two participants withdrew from the study early. Urine analyses were positive for D-AMP in all urine samples and therapy sessions, except in two patients who did not take LDX on a daily basis. D-AMP was detected in all hair samples; however, no correlation was found between prescribed dose/day and D-AMP concentrations in proximal hair segments. Qualitative interpretation of hair analysis showed that 18 of the 22 study completers were compliant concerning the intake of LDX without additional consumption of illegal D,L-AMP. Analysis of urine taken during the therapy sessions showed no correlation between D-AMP concentrations and prescribed dosage, with or without normalization for creatinine. In conclusion, chiral LC-MS/MS hair analysis might represent a non-invasive way to confirm LDX use within the approximate period covered by the hair segment tested, but it does not allow for quantitative therapeutic drug monitoring because of interindividual variability of concentrations in hair. Drug concentrations in hair at different stages of long-term treatment should thus be interpreted with caution by clinicians and forensic experts alike when making assessments of treatment adherence.

Topics: Adult; Ambulatory Care; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Chromatography, Liquid; Dose-Response Relationship, Drug; Drug Monitoring; Female; Hair; Hair Analysis; Humans; Lisdexamfetamine Dimesylate; Male; Medication Adherence; Middle Aged; Reproducibility of Results; Tandem Mass Spectrometry; Treatment Outcome; Young Adult

Although there is no pharmacological treatment for autism spectrum disorder (ASD) itself, behavioral and pharmacological therapies have been used to address its symptoms and common comorbidities. A better understanding of the medications used to manage comorbid conditions in this growing population is critical; however, most previous efforts have been limited in size, duration, and lack of broad representation.. To use a nationally representative database to uncover trends in the prevalence of co-occurring conditions and medication use in the management of symptoms and comorbidities over time among US individuals with ASD.. This retrospective, population-based cohort study mined a nationwide, managed health plan claims database containing more than 86 million unique members. Data from January 1, 2014, to December 31, 2019, were used to analyze prescription frequency and diagnoses of comorbidities. A total of 26 722 individuals with ASD who had been prescribed at least 1 of 24 medications most commonly prescribed to treat ASD symptoms or comorbidities during the 6-year study period were included in the analysis.. Diagnosis codes for ASD based on International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision.. Quantitative estimates of prescription frequency for the 24 most commonly prescribed medications among the study cohort and the most common comorbidities associated with each medication in this population.. Among the 26 722 individuals with ASD included in the analysis (77.7% male; mean [SD] age, 14.45 [9.40] years), polypharmacy was common, ranging from 28.6% to 31.5%. Individuals' prescription regimens changed frequently within medication classes, rather than between classes. The prescription frequency of a specific medication varied considerably, depending on the coexisting diagnosis of a given comorbidity. Of the 24 medications assessed, 15 were associated with at least a 15% prevalence of a mood disorder, and 11 were associated with at least a 15% prevalence of attention-deficit/hyperactivity disorder. For patients taking antipsychotics, the 2 most common comorbidities were combined type attention-deficit/hyperactivity disorder (11.6%-17.8%) and anxiety disorder (13.1%-30.1%).. This study demonstrated considerable variability and transiency in the use of prescription medications by US clinicians to manage symptoms and comorbidities associated with ASD. These findings support the importance of early and ongoing surveillance of patients with ASD and co-occurring conditions and offer clinicians insight on the targeted therapies most commonly used to manage co-occurring conditions. Future research and policy efforts are critical to assess the extent to which pharmacological management of comorbidities affects quality of life and functioning in patients with ASD while continuing to optimize clinical guidelines, to ensure effective care for this growing population.

Topics: Adolescent; Amphetamines; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bupropion; Child; Child, Preschool; Cohort Studies; Comorbidity; Data Mining; Depressive Disorder, Major; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Female; Health Services Accessibility; Humans; Insurance; Lisdexamfetamine Dimesylate; Male; Managed Care Programs; Prevalence; Retrospective Studies

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.

Topics: Abdomen; Abdominal Pain; Antidepressive Agents; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bezoars; Child; Constipation; Diagnosis, Differential; Foreign Bodies; Humans; Lisdexamfetamine Dimesylate; Male; Quetiapine Fumarate; Radiography, Abdominal; Tomography, X-Ray Computed

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.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Trichotillomania

Lack of consensus regarding how best to define treatment response hinders translation from trials to the clinic. These post hoc analyses examine three commonly used response criteria in six trials of lisdexamfetamine dimesylate (LDX) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD).. Data from four short-term randomised controlled trials (RCTs) and two long-term open-label studies were analysed. Children and adolescents with ADHD received either dose-optimised (30-70 mg/day) or fixed-dose (70 mg/day) LDX. The RCTs included osmotic-release oral system methylphenidate (OROS-MPH) or atomoxetine (ATX) as a head-to-head comparator or as a reference treatment. Three definitions of response were used in these analyses: reductions of ⩾30% or ⩾50% in ADHD Rating Scale IV (ADHD-RS-IV) total score plus a Clinical Global Impressions - Improvement (CGI-I) score of 1 or 2, or an ADHD-RS-IV total score of ⩽18.. At the end point, LDX response rates for the least stringent criterion of ⩾30% reduction in ADHD-RS-IV total score plus a CGI-I score of 1 or 2 ranged from 69.6% to 82.6%. The proportion achieving the more stringent criterion of a reduction in ADHD-RS-IV total score of ⩾50% plus a CGI-I score of 1 or 2 at the end point ranged from 59.8% to 74.8%. An ADHD-RS-IV total score of ⩽18 at the end point was achieved by 56.7-79.9% of participants. Response rates remained stable throughout the long-term open-label studies.. Response rates were similar for the two more stringent response criteria. The less stringent criterion resulted in higher response rates and may include partial responders.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Data Interpretation, Statistical; Female; Humans; Lisdexamfetamine Dimesylate; Male; Outcome Assessment, Health Care

Rely on DSM-5 criteria and an appropriate rating scale to assess how an individual's inattention, hyperactivity, and impulsivity interfere with functioning in different settings.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Behavior Therapy; Central Nervous System Stimulants; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Late Onset Disorders; Lisdexamfetamine Dimesylate; Male; Practice Guidelines as Topic; Young Adult

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.. 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.. 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.. 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.. 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.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Dextroamphetamine; Dose-Response Relationship, Drug; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Retrospective Studies; Time Factors

This study examined the prescribing patterns of attention-deficit hyperactivity disorder (ADHD) medications in Ireland between 2005 and 2015 in children, adolescents and young adults, and concomitant use of psychotropic medication.. Repeated cross-sectional study.. Community setting using pharmacy claims data in Ireland.. Children and young adults aged 0-24 years.. Authorised medications used to treat ADHD during the study period, methylphenidate, dexamfetamine, lisdexamfetamine dimesylate and atomoxetine were extracted from a national pharmacy claims database. Dispensing of concomitant psychotropic medications including antipsychotics, anxiolytics, hypnotics/sedatives and antidepressants were examined.. The number on any ADHD medication ranged from 1913 in 2005 to 4853 in 2015, and the prevalence rate per 1000 eligible population aged <25 years increased significantly over time from 5.61 (95% CI 5.36 to 5.86) in 2005 to 8.36 (95% CI 8.13 to 8.60) in 2015 (p<0.0001). Negative binomial regression showed significant changes over time for ADHD prescribing (p<0.001), with significantly higher rates across the different age groups. The rates overall were three to five times higher in males. There was a significant increase in the percentage on concomitant antidepressants from 2% in 2005 to 6% in 2015 (p<0.001).. There were significantly higher rates of ADHD prescribing in children/adolescents and a significant increase in the coprescribing of antidepressants. The reasons for the increase are unclear but may reflect increasing awareness and diagnosis of the condition.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child, Preschool; Cross-Sectional Studies; Dextroamphetamine; Female; Humans; Hypnotics and Sedatives; Infant; Infant, Newborn; Ireland; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Practice Patterns, Physicians'; Young Adult

Topics: Adult; Amphetamine-Related Disorders; Attention Deficit Disorder with Hyperactivity; Blood Platelets; Drug Overdose; Fever; Humans; Lisdexamfetamine Dimesylate; Male; Thrombocytopenia; Valproic Acid

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Lisdexamfetamine Dimesylate; Quality of Life

Lisdexamfetamine dimesylate, a prodrug of d-amphetamine, has been approved for treatment of attention-deficit/hyperactivity disorder (ADHD). The purposes of this study were constructing a population pharmacokinetic model of d-amphetamine after dosing of lisdexamfetamine dimesylate and assessing influential factors on the pharmacokinetics of d-amphetamine in Japanese pediatric patients with ADHD. Additionally, the exposure-response relationship was evaluated for Japanese pediatric patients with ADHD using a clinical rating scale, the ADHD Rating Scale IV (ADHD RS-IV, efficacy endpoint) total score as a response index. A total of 1365 points of plasma d-amphetamine concentrations from pediatric patients (6-17 years) with ADHD in clinical studies conducted in Japan and the US were employed for the population pharmacokinetic analysis. The plasma concentrations of d-amphetamine in pediatric patients with ADHD were well described by a one-compartment model with first-order absorption and lag time. The effects of body weight and ethnicity (Japanese or non-Japanese) on apparent total body clearance and the effect of body weight on apparent volume of distribution were incorporated into the final model. No clear exposure-dependent reduction was evident from the ADHD RS-IV total score, whereas the reductions were greater for the lisdexamfetamine dimesylate treatment groups compared with the placebo group regardless of exposure to d-amphetamine.

Topics: Administration, Oral; Adolescent; Age Factors; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Japan; Lisdexamfetamine Dimesylate; Male; Models, Biological; Prodrugs; United States

Topics: Attention Deficit Disorder with Hyperactivity; Capsules; Child; Dextroamphetamine; Humans; Japan; Lisdexamfetamine Dimesylate

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Practice Guidelines as Topic; United Kingdom

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Female; Humans; Insurance Claim Review; Lisdexamfetamine Dimesylate; Male; Medicaid; Methylphenidate; Retrospective Studies; Texas; United States

The aim of the study was to help quantify the protective effects of stimulant treatment on important functional outcomes in attention-deficit/hyperactivity disorder (ADHD) using the number needed to treat (NNT) statistic and examine whether these effects are moderated by sex.. Subjects were derived from three independent samples, two similarly designed case-control, 10-year prospective follow-up studies of boys and girls with and without ADHD grown up and a cross-sectional randomized clinical trial of lisdexamfetamine on driving performance and behavior. For all studies, subjects were evaluated with structured diagnostic interviews. To measure psychopharmacologic treatment in the follow-up studies, we collected information about each subject's stimulant medication use, age at onset, and age at termination of treatment. Subjects in the driving study underwent two driving simulation assessments (premedication and after 6 weeks of treatment on lisdexamfetamine or placebo). For each outcome, we ran a logistic regression model that included an interaction between sex and treatment status. Lifetime rates were used to calculate the NNT statistic. We also calculated adjusted NNT statistics that accounted for sex, age, socioeconomic status, and family intactness.. The NNTs were very low, ranging from 3 to 10. No interaction effects with sex were detected (all p > .05). The adjusted NNTs mostly remained the same with the exception of any substance use disorder, which increased after controlling for age.. Stimulants have strong protective effects on functional outcomes in youth with ADHD that are not moderated by sex. These results support the critical importance of early identification and treatment of children with ADHD of both sexes.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Automobile Driver Examination; Case-Control Studies; Central Nervous System Stimulants; Cross-Sectional Studies; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Male; Prospective Studies; Randomized Controlled Trials as Topic; Sex Factors

Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high-pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug-facilitated crime (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine.

Topics: Amphetamine; Attention Deficit Disorder with Hyperactivity; Chromatography, High Pressure Liquid; Forensic Toxicology; Hair; Humans; Illicit Drugs; Lisdexamfetamine Dimesylate; Retrospective Studies; Stereoisomerism

To examine real-world prescription medication usage among commercially-insured adults with attention deficit/hyperactivity disorder (ADHD) in the US.. Adults with ADHD who received ≥1 ADHD medication during 2013 were identified from a large US claims database. Combination therapy was defined as an overlap of ≥30 days between the index (first treatment ≥30 days in 2013) and another medication(s). Patients were classified into six groups: long-acting (LA) monotherapy, short-acting (SA) monotherapy, LA + LA, SA + SA, LA + SA, and >2 therapies. Analyses compared baseline characteristics by regimen, ranked combination regimens, and estimated daily average consumption (DACON) for monotherapy users.. Of 206,443 adults with ADHD (mean age = 32.9 years; 51.6% female), 56.9% used LA monotherapy, 30.7% SA monotherapy, and 12.5% used combination therapies (LA + SA: 10.3%; LA + LA: 1.3%; SA + SA: 0.4%; >2 therapies: 0.5%). Extended-release mixed amphetamine salts (MAS-XR, 39.2%) and lisdexamfetamine (LDX, 31.5%) were the most common LA monotherapies. Nearly all SA monotherapy patients received immediate-release mixed amphetamine salts (MAS-IR; 81.7%). The top three therapies among combination categories were: (a) LA + LA: branded MAS-XR + generic MAS-XR (13.7%), LDX + generic MAS-XR (10.8%), LDX + guanfacine ER (10.7%); (b) SA + SA: generic MAS-IR + clonidine IR (33.5%), generic MAS-IR + generic MPH SA (17.9%), branded MAS-IR + generic MAS-IR (11.1%); (c) LA + SA: generic MAS-XR+/-IR (39.2%), LDX + generic MAS-IR (16.7%), LA + SA generic MPH (12.6%). Among monotherapy users, DACON was 1.2 ± 0.6 (LA) and 2.1 ± 0.9 (SA) tablets.. There is significant treatment heterogeneity among US adults with ADHD. A sizable proportion of patients received monotherapies at above the recommended dosages or combination therapies, suggesting existing single-tablet regimens may not meet patients' needs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; United States; Young Adult

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Drug Approval; Humans; Lisdexamfetamine Dimesylate; United States; United States Food and Drug Administration

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Humans; Lisdexamfetamine Dimesylate; Male; Raynaud Disease

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults.. Estimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX).. A 1-year decision-analytic model was developed. Health outcomes included response, non-response and inability to tolerate. Efficacy data were obtained from a mixed-treatment comparison (MTC). Response was a score of 1 or 2 on the Clinical Global Impression-Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utilities were identified via a systematic literature review. Health care resource use estimates were obtained via a survey of clinicians. Daily drug costs were estimated from mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses (PSAs) were performed.. LDX dominated MPH-ER and ATX; reducing mean per-patient annual cost by £5 and £200, and increasing mean quality-adjusted life years (QALYs) by 0.005 and 0.009, respectively. In the PSA, the probability of cost-effectiveness for LDX vs. MPH-ER and ATX at a threshold of £20,000 per QALY was 61% and 80%, respectively.. From the perspective of the UK NHS, LDX is likely to provide a cost-effective treatment for adults with ADHD. This conclusion may be drawn with more certainty in comparison with ATX than with MPH-ER.

Topics: Adult; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cost-Benefit Analysis; Humans; Lisdexamfetamine Dimesylate; Review Literature as Topic; Treatment Outcome; United Kingdom

Psychostimulants are considered first-line pharmacotherapy for youth with attention-deficit/hyperactivity disorder (ADHD), but questions remain regarding the comparative efficacy of amphetamine- and methylphenidate-based agents.. Our objective was to describe two acute randomized, double-blind, placebo-controlled, head-to-head studies of lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) in adolescents with ADHD.. Adolescents (13-17 years) diagnosed with ADHD according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were enrolled in an 8-week flexible-dose study [LDX 30-70 mg/day (n = 186 randomized); OROS-MPH 18-72 mg/day (n = 185 randomized); placebo (n = 93 randomized)] or a 6-week forced-dose study [LDX 70 mg/day (n = 219 randomized); OROS-MPH 72 mg/day (n = 220 randomized); placebo (n = 110 randomized)]. Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) total score changes from baseline (primary endpoint) at week 8 (flexible-dose study) or week 6 (forced-dose study) were assessed with mixed-effects models for repeated measures. Secondary endpoints included improvement on the dichotomized Clinical Global Impressions-Improvement scale (CGI-I; key secondary endpoint) and changes from baseline on the ADHD-RS-IV subscales. Safety assessments included treatment-emergent adverse events (TEAEs) and vital signs.. Least squares (LS) mean ± standard error of the mean (SEM) ADHD-RS-IV total score changes from baseline to end of treatment were -17.0 ± 1.03 with placebo, -25.4 ± 0.74 with LDX, and -22.1 ± 0.73 with OROS-MPH in the forced-dose study and -13.4 ± 1.19 with placebo, -25.6 ± 0.82 with LDX, and -23.5 ± 0.80 with OROS-MPH in the flexible-dose study. LS mean ± SEM treatment difference for the change from baseline significantly favored LDX over OROS-MPH in the forced-dose [-3.4 ± 1.04, p = 0.0013, effect size (ES) -0.33] but not the flexible-dose (-2.1 ± 1.15, p = 0.0717, ES -0.20) study. The percentage of improved participants on the dichotomized CGI-I at end of treatment was significantly greater with LDX than with OROS-MPH in the forced-dose study (81.4 vs. 71.3%, p = 0.0188) but not the flexible-dose study (LDX 83.1%, OROS-MPH 81.0%, p = 0.6165). The LS mean ± SEM treatment differences for change from baseline on the ADHD-RS-IV hyperactivity/impulsivity and inattentiveness subscales nominally favored LDX in the forced-dose study (hyperactivity/impulsivity subscale -1.3 ± 0.49, nominal p = 0.0081, ES -0.27; inattentiveness subscale -2.0 ± 0.63, nominal p = 0.0013, ES -0.33), but there were no significant differences between active treatments in the flexible-dose study. In both studies, LDX and OROS-MPH were superior to placebo for all efficacy-related endpoints (all nominal p < 0.0001; ES range -0.43 to -1.16). The overall frequency of TEAEs for LDX and OROS-MPH, respectively, were 66.5 and 58.9% in the forced-dose study and 83.2 and 82.1% in the flexible-dose study. TEAEs occurring in ≥ 5% of participants that were also reported at two or more times the rate of placebo were decreased appetite, decreased weight, insomnia, initial insomnia, dry mouth, and nasopharyngitis (LDX and OROS-MPH), irritability and dizziness (LDX only), and increased heart rate (OROS-MPH only) in the forced-dose study and decreased appetite, decreased weight, insomnia, and dizziness (LDX and OROS-MPH) and dry mouth and upper abdominal pain (LDX only) in the flexible-dose study. Mean ± standard deviation (SD) increases from baseline in vital signs (systolic and diastolic blood pressure, pulse) were observed in the forced-dose study [LDX 1.6 ± 9.65 and 3.3 ± 8.11 mmHg, 6.7 ± 12.78 beats per minute (bpm); OROS-MPH 2.6 ± 10.15 and 3.3 ± 9.13 mmHg, 7.6 ± 12.47 bpm] and the flexible-dose study (LDX 2.4 ± 9.46 and 2.8 ± 8.41 mmHg, 4.7 ± 11.82 bpm; OROS-MPH 0.4 ± 9.90 and 2.2 ± 8.64 mmHg, 6.. LDX was superior to OROS-MPH in adolescents with ADHD in the forced-dose but not the flexible-dose study. Safety and tolerability for both medications was consistent with previous studies. These findings underscore the robust acute efficacy of both psychostimulant classes in treating adolescents with ADHD. CLINICALTRIALS.. NCT01552915 and NCT01552902.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Delayed-Action Preparations; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Randomized Controlled Trials as Topic; Treatment Outcome

Attention deficit hyperactivity disorder (ADHD) is an increasingly common diagnosis of childhood that manifests with symptoms that affect cognitive, academic, behavioral, emotional, and social functioning. There are a multitude of pharmaceutical therapies to choose from when managing this condition, and though many studies on the safety and efficacy of these medications have been published, adverse effects still occur.. This case discusses a previously healthy 8-year-old boy who had been prescribed 20-mg lisdexamfetamine dimesylate for ADHD however mistakenly took his brother's 36-mg methylphenidate extended-release tablets, resulting in hyperhidrosis, excessive thirst, polydipsia, and combative behavior that began within 3 hours of ingestion. He was evaluated at a community hospital emergency department and given lorazepam due to agitation and combativeness before discharge. However, he returned with hypothermia, hyponatremia, and status epilepticus resulting in intubation. Patient was transferred to our facility where a computer tomography of his head was negative and hyponatremia was corrected with 3% NaCl saline solution. A lumbar puncture was performed due to temperature instability before starting broad-spectrum antibiotics. Cerebrospinal fluid findings were normal, and he was extubated at 18 hours postingestion. Patient was discharged home after 3 days with no residual symptoms.. Though both lisdexamfetamine dimesylate and methylphenidate are widely used among pediatricians today for treatment of ADHD, reports of life-threatening water intoxication as a result of overdose is rare. Studies have reported that severe 3,4-methylenedioxymethamphtamine toxicity in adults is associated with syndrome of inappropriate diuretic hormone (SIADH) secretion, hyponatremia, and seizures, along with serotonin-induced transient elevation in antidiuretic hormone. Adult schizophrenics who receive psychostimulants have also been shown to develop polydipsia with hyponatremia. Although the use of psychostimulants in adult schizophrenic patients has been studied, literature on toxicity and effects in the pediatric psychiatric population is scarce. We would suggest that this patient's polydipsia and hyponatremia are most likely a result of his ingestion of a toxic dose of a long-acting agent known to cause secondary psychosis.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Humans; Hyponatremia; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Phenytoin; Polydipsia; Sodium Chloride; Treatment Outcome; Water Intoxication

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in children, with worldwide prevalence of ADHD varying from 5.9 to 7.1 %, depending on the reporter. In case of inadequate response to stimulants, combination therapy of stimulants and an adjunctive medication may improve the control of ADHD symptoms, reduce the dose-limiting adverse events, and help control comorbidities. To date, the only medication to be used for adjunctive therapy to psychostimulants is guanfacine extended release (GXR). The aim of this study was to assess the economic impact of GXR as an adjunct therapy with long-acting stimulants (GXR + stimulant) compared to long-acting stimulant monotherapy (stimulant alone) in the treatment of children and adolescents with ADHD in Canada.. A Markov model was developed using health states defined based on the clinician-reported Clinical Global Impression-Severity (CGI-S) score (normal, mild, moderate, severe). Transition probabilities were calculated based on patient-level data from a published study. Long-acting stimulants available in Canada were considered in the base-case model: amphetamine mixed salts, methylphenidate HCl formulations, and lisdexamfetamine dimesylate. Analyses were conducted from a Canadian Ministry of Health (MoH; Ontario) and a societal perspective over a 1-year time horizon with weekly cycles.. Over a 1-year time horizon, GXR + stimulant was associated with 0.655 quality-adjusted life year (QALY), compared to 0.627 QALY with stimulant alone, for a gain of 0.028 QALY. From a MoH perspective, GXR+ stimulant and stimulant alone were associated with total costs of $CA1,617 and $CA949, respectively (difference of $CA668), which resulted in an incremental cost-effectiveness ratio (ICER) of $CA23,720/QALY. From a societal perspective, GXR + stimulant and stimulant alone were associated with total costs of $CA3,915 and $CA3,582, respectively (difference of $CA334), which resulted in an ICER of $CA11,845/QALY. Probabilistic sensitivity analysis (PSA) of GXR + stimulant showed that it remains a cost-effective strategy in 100 % of the simulations from both perspectives in numerous PSA and one-way sensitivity analyses, relative to a willingness to pay threshold of $50,000/QALY.. This economic evaluation demonstrates that GXR +  stimulant is cost-effective compared to stimulant alone in the treatment of children and adolescents with ADHD in Canada.

Topics: Amphetamine; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cost-Benefit Analysis; Delayed-Action Preparations; Drug Costs; Drug Therapy, Combination; Female; Guanfacine; Health Care Costs; Humans; Lisdexamfetamine Dimesylate; Male; Markov Chains; Methylphenidate; Ontario; Quality-Adjusted Life Years

Lisdexanfetamine (LDX) is the drug for attention deficit hyperactivity disorder (ADHD) undergoing the largest research volume in the latest years. However, no studies certify its usefulness for the improvement of cognitive functioning in ADHD.. To evaluate the efficacy of LDX in the behavioral and cognitive improvement of a group of patients with ADHD. Such efficacy was measured by means of the administration of AULA Nesplora virtual reality test before the prescription of pharmacological treatment and right after the treatment with LDX.. The sample comprised 85 patients between 6 and 16 years, with clinical diagnosis of ADHD, who attended treatment in a neuropediatrics consultation. All patients started pharmacological treatment with the proper dose of LDX after the clinical interview and the first administration of AULA test. After an average treatment of 7.5 months, AULA was administered again and the treatment progress based on cognitive and motor symptomatology was assessed.. Results showed highly significant improvements in selective and sustained attention, quality of attention focus and hyperactivity; moderate improvements in impulsivity; and an incidence close to zero in processing speed.. LDX constitutes an adequate treatment for the substantial improvement of attention and hyperactivity; such improvement can be monitored accurately by means of AULA virtual reality test.. Eficacia de la lisdexanfetamina en la mejora sintomatica conductual y cognitiva del trastorno por deficit de atencion/ hiperactividad: tratamiento monitorizado mediante el test AULA Nesplora de realidad virtual.. Introduccion. La lisdexanfetamina (LDX) es el farmaco para el trastorno por deficit de atencion/hiperactividad (TDAH) con mayor volumen de investigacion de los ultimos años. No obstante, no hay estudios que certifiquen su utilidad para la mejoria del funcionamiento cognitivo en el TDAH. Objetivo. Evaluar la eficacia de la LDX en la mejora sintomatica conductual y cognitiva en un grupo de pacientes con TDAH. Dicha eficacia fue medida mediante la administracion del test AULA Nesplora de realidad virtual antes de la prescripcion del tratamiento farmacologico y despues del tratamiento con LDX. Pacientes y metodos. La muestra estaba compuesta por 85 pacientes de 6-16 años, con diagnostico clinico de TDAH y que asistian a tratamiento en una consulta de neuropediatria. Todos los pacientes iniciaron el tratamiento farmacologico con la correspondiente dosis de LDX tras la entrevista clinica y la primera administracion del test AULA. Tras un tratamiento medio de 7,5 meses, se les administro AULA nuevamente y se valoro el progreso del tratamiento farmacologico sobre la sintomatologia cognitiva y motora. Resultados. Se apreciaron mejorias muy significativas en la atencion selectiva y sostenida, la calidad del foco atencional y la hiperactividad, mejorias moderadas en la impulsividad, y una incidencia casi nula en la velocidad de procesamiento. Conclusiones. La LDX constituye un tratamiento adecuado para la mejora sustancial de la atencion e hiperactividad, y dicha mejora puede monitorizarse de forma precisa mediante el test de realidad virtual AULA.

Topics: Adolescent; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cognition; Disruptive, Impulse Control, and Conduct Disorders; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

An economic analysis from the perspective of the UK National Health Service (NHS) evaluated the cost effectiveness of lisdexamfetamine dimesylate (LDX) compared with atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder who have had an inadequate response to methylphenidate.. A 1-year decision-analytic model was constructed, with the health outcomes "response", "nonresponse", and "unable to tolerate". Clinical data were taken from a head-to-head, randomized controlled trial in inadequate responders to methylphenidate. Response to treatment was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impression-Improvement subscale. Tolerability was assessed by discontinuation rates owing to adverse events. Utility weights were identified via a systematic literature review. Healthcare resource use estimates were obtained via a survey of clinicians. Daily drug costs were derived from British National Formulary 2012 costs and mean doses reported in the trial. One-way and probabilistic sensitivity analyses (PSAs) were performed.. The comparison of LDX with atomoxetine resulted in an estimate of an incremental cost-effectiveness ratio of £1802 per quality-adjusted life-year (QALY). The result was robust in a wide range of sensitivity analyses; results were most sensitive to changes in drug costs and efficacy. In the PSA, assuming a maximum willingness to pay of £20,000 per QALY, LDX versus atomoxetine had an 86 % probability of being cost effective. In 38 % of PSA runs, LDX was more effective and less costly than atomoxetine.. From the perspective of the UK NHS, LDX provides a cost-effective treatment option for children and adolescents who are inadequate responders to methylphenidate.

Topics: Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Cost-Benefit Analysis; Female; Health Resources; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Probability; Quality-Adjusted Life Years; Treatment Outcome

A 17-year-old male with ADHD who was treated with sertraline and lisdexamfetamine presented with transient episodes of speech impairment and right-sided hemiparesis preceded by headaches. Magnetic resonance imaging revealed three cerebral ischaemic lesions. Treatment was initiated with aspirin and discontinued with lisdexamfetamine. In the literature a causal relationship between treatment with central stimulants and the development of cerebrovascular events has not been substantiated. Vasospasm and paroxystic tachycardia may be associated with the event, but lisdexamfetamine and sertraline cannot be ruled out as risk factors.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cerebral Infarction; Depressive Disorder; Diffusion Magnetic Resonance Imaging; Humans; Lisdexamfetamine Dimesylate; Male; Selective Serotonin Reuptake Inhibitors; Sertraline

Attention deficit hyperactivity disorder (ADHD) is a disorder of a biological origin affecting the neurodevelopment of the brain. It is estimated that 3-7% of school-age children present ADHD. The most commonly used pharmacological treatments are amphetamines and methylphenidate (MPH). Although response rates to MPH are high, full remission rates reach only 56%. The 25% of patients who do not respond to MPH would show a response to other stimulants and vice-versa. AIMS. To clinically evaluate patients by detecting inadequate responses and the efficacy of a change to lisdexamfetamine dimesylate (LDX).. The study was prospective and observation-based. Inadequate responses were considered to be those that presented non-coverage or no effect. The Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) and Clinical Global Impression-Severity (CGI-S) assessment scales were used for the clinical assessment, together with the Weiss Functional Impairment Rating Scale (WFIRS) and the Child Health and Illness Profile (CHIP-AE). Data regarding adverse side effects were also collected.. Forty-one patients met criteria for inadequate response to treatment: 13.6 ± 3.4 years, 54.6 ± 13.2 kg, 158.5 ± 17.2 cm and body mass index of 20.9 ± 3.5 kg/m2. Reasons for change (non-exclusive): non-coverage (76%), lack of intensity of effect (68%) and presence of adverse side effects with the previous medication (16%). The mean score both at baseline and at nine months, on the ADHD-RS, was 24.54 ± 6.3 versus 12.01 ± 3.2 (p < 0.01), respectively, and for the CGI-S values were 5.09 ± 0.5 versus 2.91 ± 0.8 (p < 0.01), respectively. The safety profile coincided with that of other stimulant-based treatments for ADHD.. When the response to MPH presents non-coverage or lack of effect, changing to LDX has proved to be effective, with an improvement in 86.7% of cases, which is similar to that of other studies. It is therefore a good therapeutic option in these patients.. Cambio en la estrategia terapeutica ante una respuesta inadecuada al tratamiento farmacologico para el trastorno por deficit de atencion/hiperactividad.. Introduccion. El trastorno por deficit de atencion/hiperactividad (TDAH) es un trastorno del neurodesarrollo cerebral de origen biologico. Se estima que el 3-7% de los niños en edad escolar presentan TDAH. Dentro del tratamiento farmacologico, las anfetaminas y el metilfenidato (MPH) son los mas utilizados. Aunque las tasas de respuesta al MPH son altas, las tasas de remision completa llegan solo al 56%. Un 25% de los pacientes que no responden al MPH si lo haria a otros estimulantes, y viceversa. Objetivo. Valorar clinicamente a los pacientes con deteccion de respuestas inadecuadas y la eficacia de un cambio a lisdexanfetamina dimesilato (LDX). Pacientes y metodos. Estudio observacional prospectivo. Se considero respuesta inadecuada al MPH aquella que presentaba falta de cobertura o de efecto. Se utilizaron las escalas de evaluacion Attention-Deficit/Hyperactivity Disorder Rating Scale IV (ADHD-RS-IV) y Clinical Global Impression-Severity (CGI-S) para la valoracion clinica, asi como la escala de evaluacion del deterioro funcional de Weiss (WFIRS) y el perfil de salud infantil (CHIP-AE). Tambien se recogieron los efectos adversos. Resultados. Cumplieron criterios de respuesta inadecuada al tratamiento 41 pacientes: 13,6 ± 3,4 años, 54,6 ± 13,2 kg, 158,5 ± 17,2 cm e indice de masa corporal de 20,9 ± 3,5 kg/m2. Motivos del cambio (no excluyentes): falta de cobertura (76%), falta de intensidad del efecto (68%) y presencia de efectos adversos con la medicacion anterior (16%). La puntuacion media basal y a los nueve meses, en la ADHD-RS, fue de 24,54 ± 6,3 frente a 12,01 ± 3,2 (p < 0,01), respectivamente, y para la CGI-S, de 5,09 ± 0,5 frente a 2,91 ± 0,8 (p < 0,01), respectivamente. El perfil de seguridad coincidio con el de otros tratamientos estimulantes para el TDAH. Conclusion. Cuando la respuesta al MPH presenta falta de cobertura o falta de efecto, el cambio a LDX se ha mostrado eficaz, con una mejoria en el 86,7% de los casos, similar a la de otros estudios, por lo que resulta una buena opcion terapeutica en estos pacientes.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Female; Humans; Lisdexamfetamine Dimesylate; Male; Prospective Studies; Treatment Failure

Attention-deficit hyperactivity disorder (ADHD) is a common neurobehavioural disorder in children. Pharmacotherapy plays a main role in multimodal treatment, albeit adverse effects are a concern. Lisdexamfetamine is a newer pharmacological option and post-marketing studies on adverse events are limited.. The aim of this study was to investigate the treatment-emergent adverse events (TEAEs) in patients receiving lisdexamfetamine in a clinical setting.. We performed a retrospective cohort study at the Department of Child and Adolescent Psychiatry of Glostrup Hospital in Copenhagen, Denmark. We included all consecutive patients >6 years old, with an ICD-10 diagnosis of ADHD who were initiated on lisdexamfetamine between May 2013 and July 2014. TEAEs were assessed by a clinician and chart audit.. Forty-three patients (91 % male) with a median age of 11 (range 8-15) years were included and received lisdexamfetamine for a median of 188 days (range 3-433). In total, 23.3 % of the patients discontinued treatment due to a TEAE. 88 % of the patients experienced at least one TEAE and the time to first TEAE ≤4 weeks in 83.8 % of the patients. A new TEAE was experienced by 39.5 % of the patients compared with the TEAEs that patients had experienced when taking previous ADHD medication. The most common TEAEs (≥ 5 %) were decreased appetite, difficulty falling asleep, tics, stomach ache and weight loss. A subjectively assessed good or good but time-limited (during the day only) effect was observed in 62.7 %.. Lisdexamfetamine treatment in this small group of patients who had received previous stimulant medication for ADHD was well tolerated and the TEAEs were consistent with findings in previous trials, although more than one third of the patients experienced TEAEs not observed with previously taken ADHD medication. Both the number of patients experiencing TEAEs and the rates of discontinuation due to TEAEs were higher than previously reported.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Female; Humans; Lisdexamfetamine Dimesylate; Male; Retrospective Studies; Treatment Outcome

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by poor attention, impulse control and hyperactivity. A significant proportion of ADHD patients are also co-morbid for other psychiatric problems including mood disorders and these patients may be managed with a combination of psychostimulants and anti-depressants. While it is generally accepted that enhanced catecholamine signalling via the action of psychostimulants is likely responsible for the cognitive improvement in ADHD, other neurotransmitters including acetylcholine and histamine may be involved. In the present study, we have examined the effect of lisdexamfetamine dimesylate (LDX), an amphetamine pro-drug that is approved for the treatment of ADHD on acetylcholine and histamine efflux in pre-frontal cortex and hippocampus alone and in combination with the anti-depressant s-citalopram. LDX increased cortical acetylcholine efflux, an effect that was not significantly altered by co-administration of s-citalopram. Cortical and hippocampal histamine were markedly increased by LDX, an effect that was attenuated in the hippocampus but not in pre-frontal cortex when co-administered with s-citalopram. Taken together, these results suggest that efflux of acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially influenced by the co-administration of s-citalopram. Attention deficit hyperactivity disorder (ADHD) is characterized by poor attention, impulse control and hyperactivity. Some ADHD patients are also co-morbid for mood disorders and may be managed with psychostimulants (e.g. lisdexamfetamine, LDX) and anti-depressants (e.g. s-citalopram). LDX increased the efflux of acetylcholine and histamine, neurotransmitters involved in cognitive function, which were differentially influenced when co-administered with s-citalopram. Acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially affected by the co-administration of s-citalopram.

Topics: Acetylcholine; Animals; Antidepressive Agents, Second-Generation; Attention Deficit Disorder with Hyperactivity; Citalopram; Dextroamphetamine; Drug Therapy, Combination; Hippocampus; Histamine Release; Lisdexamfetamine Dimesylate; Male; Microdialysis; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Treatment Outcome

To develop a risk score for treatment failure that could potentially be used to individualize treatment selection between lisdexamfetamine dimesylate (LDX) and osmotic-release oral system methylphenidate (OROS-MPH) in children and adolescents with attention deficit/hyperactivity disorder (ADHD).. The study used data from patients with ADHD receiving LDX (N = 104) or OROS-MPH (N = 107) in a phase III randomized clinical trial. A prediction model was developed to estimate risk scores for failing OROS-MPH, where treatment failure was defined as less than 25% improvement in the ADHD Rating Scale IV total score from baseline. Patients were ranked by their predicted risks of OROS-MPH failure to define high-risk subpopulations. Outcomes of LDX and OROS-MPH were compared within subpopulations.. The prediction model for OROS-MPH failure selected seven predictors (age, disease duration, and five ADHD Rating Scale IV item scores) and had an in-sample C statistic of 0.860. Among all patients, LDX had a 17% (95% confidence interval 7.1%-27.8%) lower treatment failure rate than that of OROS-MPH; differences in failure rates ranged from 17% to 43% across subpopulations, increasingly enriched for high-risk patients. Similar heterogeneity across subgroups was observed for other efficacy measures.. In the overall trial population, LDX was associated with a lower rate of treatment failure compared with OROS-MPH in patients with ADHD. A more pronounced benefit of LDX over OROS-MPH was observed among subpopulations with a higher predicted risk of failing OROS-MPH. The present study showed the feasibility of individualizing treatment selection. Future research is needed to prospectively verify these results.

Topics: Administration, Oral; Adolescent; Adolescent Behavior; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child Behavior; Clinical Trials, Phase III as Topic; Comparative Effectiveness Research; Decision Support Techniques; Feasibility Studies; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Patient Selection; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Failure

Attention-deficit/hyperactivity disorder (ADHD) on college campuses is a serious and often underdiagnosed condition. The current investigation analyzed current best practice guidelines for the management of ADHD in a mid-sized university in the Midwestern United States. Best practices were identified through a review of current evidence-based literature on ADHD management. A data collection tool was developed and used to organize data and determine adherence with best practice guidelines. Investigators revealed that policy and procedures followed best practice guidelines. Development and implementation of ADHD protocols on college campuses allows nurse practitioners to confidently provide safe, quality care to patients diagnosed with ADHD.

Topics: Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Counseling; Female; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Practice Guidelines as Topic; Students; Universities; Young Adult

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder - which may persist into adolescence and adulthood. Psychostimulants and atomoxetine (ATX) are frequently prescribed to treat ADHD in Germany. Lisdexamfetamine dimesylate (LDX) is the most recently approved ADHD medication in Germany and other European countries. Data used to support the European registration of LDX is summarised from three phase-3/3b studies in children and adolescents with ADHD. Short-term efficacy (study SPD489 - 325), maintenance of efficacy (study SPD489 - 326) and efficacy in patients who had previously responded inadequately to methylphenidate (MPH) treatment (study SPD489 - 317) were demonstrated. The safety and tolerability profile of LDX in all three European studies was shown to be in line with that of other psychostimulants used to treat patients with ADHD.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials, Phase III as Topic; Europe; Germany; Humans; Lisdexamfetamine Dimesylate

This study compared the relative effects of three treatment conditions: long-acting stimulant medication (MED), behavior modification, and medication/behavioral treatments combined (COM) in children with ADHD.. A total of 25 children, aged 6 to 12 years, received the three treatment conditions during a 7-week Summer Treatment Program in an alternating treatments design. Counselors completed behavioral ratings from 0.5 to 12.5 hr post dose, and parents completed nighttime ratings.. Ratings for SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) and for following instructions indicated COM and MED improved symptoms over BEH treatment beginning 3 hr post dose (p = .008), with ratings maintained 12.5 hr post dose (p = .001 and .006). Results for frustration tolerance indicated significant improvement in all three conditions until 9 hr post dose.. MED and COM separated from BEH at 3 hr post dose, and sustained benefit was observed across the day for two of three measures. BEH appears to have an additive effect, extending the duration of frustration tolerance.

Topics: Adolescent; Apathy; Attention Deficit Disorder with Hyperactivity; Behavior Therapy; Central Nervous System Stimulants; Child; Female; Frustration; Humans; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Parents; Prodrugs; Treatment Outcome

We evaluated the effects of white noise played through headphones on off-task behavior, percentage of items completed, and percentage of items completed correctly for 3 students with attention deficit hyperactivity disorder (ADHD). Headphones plus white noise were associated with decreases in off-task behavior relative to baseline and headphones-only (no white noise) control conditions. Little change in academic responding occurred across conditions for all participants.

Topics: Achievement; Acoustic Stimulation; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Female; Humans; Learning; Lisdexamfetamine Dimesylate; Male; Noise

To examine the clinical effects of equivalent doses of single-blind (SB; patient-blind) lisdexamfetamine (LDX) and mixed amphetamine salts-immediate release (MAS-IR) on adult attention-deficit/hyperactivity disorder (ADHD) in a placebo (PBO)-controlled, crossover design.. Twenty-four subjects were treated sequentially in a fixed order with (1) SB PBO (matching LDX) for 1 week, (2) SB LDX (up to 70 mg/day) for 5 weeks, (3) SB PBO washout for 3 weeks, and (4) open-label treatment MAS-IR (tid up to 45 mg/day) for 5 weeks. Clinical effects on ADHD and executive function were assessed weekly throughout the trial with the ADHD Rating Scale with adult prompts, the Clinical Global Impression Severity Scale (CGI-S), and the Behavior Rating Inventory of Executive Function (BRIEF).. Lisdexamfetamine and MAS-IR were generally well tolerated. Significant and equal reductions on ADHD clinician ratings were seen. Significantly greater reductions in CGI-S and selected BRIEF subsets were observed in LDX over MAS-IR treatment. However, in general, baseline scores for MAS-IR treatment did not fully return to the LDX baseline. Adherence in this structured and monitored clinical trial was good for once daily LDX and 3 times a day MAS-IR.. In this crossover study, both LDX and MAS-IR had significant effects on ADHD clinician ratings and measures of executive function (with response rates of about 80%); patients in this monitored clinical trial were adherent with once daily LDX and 3 times a day MAS-IR, which may not be the case in real-world clinical practice. The findings of some superiority of LDX over MAS-IR on the CGI-S and BRIEF ratings may be influenced by the variability in the baselines used, but nevertheless should be further investigated in larger scale, parallel-design clinical trials.

Topics: Adult; Amphetamines; Attention; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Cross-Over Studies; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Executive Function; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Salts; Single-Blind Method; Young Adult

This study explores the use of stimulant medication for parents with attention-deficit/hyperactivity disorder (ADHD) who also have adolescents with ADHD.. Five parents, diagnosed with ADHD, had their dose of lisdexamfetamine (LDX) titrated to optimal effect. Next, parents and their adolescents completed two interactions, once when parents were on placebo and once when parents were on optimal dose of LDX, to assess acute effects of parental medication on parenting during a neutral discussion (NeuDiss), a problem discussion (ProbDiss), and a homework task (HW).. Parents demonstrated a significant decrease in the ratio of commands to total verbalizations during the NeuDiss on LDX compared with placebo. Although no other statistically significant effects emerged at the p<0.05 level, moderate to large effects of medication on some aspects of parenting related to the amount and timing of speech (i.e., total verbalizations, total commands, ratio of commands to total verbalizations, and responsiveness) emerged and varied by task. Parental stimulant medication did not appear to impact the content of parents' speech (i.e., use of negative talk or praise).. These results add to a growing literature suggesting that treatment for parental ADHD may impact parenting performance, and suggest that attention to parental ADHD in treatment for adolescents with ADHD may possibly enhance family functioning.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Middle Aged; Parent-Child Relations; Parenting; Pilot Projects

Although graphomotor differences and variability of performance have been observed in children with attention deficit hyperactivity disorder (ADHD), no study has investigated whether this variability manifests in the kinematic graphomotor domain in adults with ADHD. Fourteen ADHD and 20 control participants wrote a novel grapheme and common word on a digitizing tablet 30 times each, with ADHD participants counterbalanced on and off stimulant medication. Variability of graphomotor fluency was significantly greater in ADHD versus control participants only in the novel writing task, both on, F(1,31)=5.988, p=.020, and off stimulant medication, F(1,32)=8.789, p=.006. Results suggest that motor control differences in ADHD are not limited to childhood and extend into adulthood. Given sufficient additional research, variability of kinematic graphomotor fluency may increase the sensitivity/specificity of differential diagnoses and/or represent a biomarker for ADHD.

Topics: Adolescent; Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Automation; Biomechanical Phenomena; Case-Control Studies; Central Nervous System Stimulants; Dextroamphetamine; Female; Handwriting; Humans; Intelligence Tests; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Middle Aged; Motor Skills; Reproducibility of Results; Young Adult

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobiological disorders in childhood, and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsiveness, with an estimated prevalence of 5.29%. ADHD can have a negative impact upon all areas of the life of the patient. The main clinical guides accept multimodal treatment, involving both pharmacological and psychological measures, as the best management approach in ADHD (psychoeducational, behavioural and academic). Lisdexamfetamine dimesylate (LDX) is a new drug for the treatment of ADHD. A multidiscipline expert document has been developed, compiling the scientific evidence referred to this new molecule. The study also addresses the existing shortcomings in current drug therapy for ADHD and the contributions of LDX to routine clinical practice, in an attempt to help and guide physicians in the use of this new treatment. This document is endorsed by the ADHD and Psychoeducational Development task Group of the Spanish Society of Primary Care Pediatrics (Grupo de TDAH y Desarrollo Psicoeducativo de la Asociación Española de Pediatría de Atención Primaria, AEPap), the Spanish Society of Pediatric Neurology (Sociedad Española de Neurología Pediátrica, SENEP) and the Spanish Society of Out-hospital Pediatrics and Primary Care (Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria, SEPEAP).

Topics: Attention Deficit Disorder with Hyperactivity; Dopamine Uptake Inhibitors; Humans; Lisdexamfetamine Dimesylate; Prodrugs

To assess treatment adherence in attention deficit/hyperactivity disorder (ADHD) patients initiated on Lisdexamfetamine (LDX) vs other FDA-approved stimulants and non-stimulant medications.. ADHD patients initiated on an ADHD medication (index medication) were selected from a large US administrative claims database. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (over 18 years old), and previously treated adults. Furthermore, based on their index medication, patients were classified into seven mutually exclusive treatment groups: LDX, atomoxetine (ATX), osmotic release methylphenidate hydrochloride long acting (OROS MPH), other methylphenidate/dexmethylphenidate long acting (MPH LA) and short acting (MPH SA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long acting (AMPH LA). Treatment adherence (proportion of days covered by the index medication ≥0.8) over a 12-month period was compared across treatment groups using multivariate logistic regression models.. In children and adolescents, LDX patients were more likely to be adherent compared to patients in each of the other treatment groups, except in treatment-naïve patients where LDX patients had a similar likelihood (p = 0.6925) and were less likely (p = 0.0004) to be adherent compared to ATX and OROS MPH patients, respectively. In adults, the LDX treatment group was also more likely to be adherent compared to each of the other treatment groups, except compared to AMPH LA, where statistically insignificant differences were observed (previously treated: p = 0.6471, treatment-naïve: p = 0.0733).. ADHD severity information was not available in the database. Accordingly, this study did not control for ADHD severity.. Overall, LDX-treated patients demonstrated a better treatment adherence compared to patients initiated on other ADHD medications, except for AMPH LA in adult and OROS MPH and ATX in treatment-naïve children and adolescents.

Topics: Adolescent; Adult; Age Distribution; Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Family Health; Female; Humans; Insurance Claim Review; Lisdexamfetamine Dimesylate; Longitudinal Studies; Male; Medication Adherence; Retrospective Studies; Sex Distribution; United States

To compare therapy augmentation and deviation rates from the recommended once-daily dosing regimen in Attention Deficit Hyperactivity Disorder (ADHD) patients initiated on lisdexamfetamine (LDX) vs other once-daily Food and Drug Administration (FDA) approved stimulants.. ADHD patients initiated on a long-acting ADHD stimulant medication (index medication) in/after 2007 were selected from a large U.S. administrative claims database. Patients were required to be persistent for ≥90 days and continuously enrolled in their healthcare plan for ≥12 months following treatment initiation date. Based on age and previous treatment status, patients were classified into treatment-naïve children and adolescents (6-17 years old), previously treated children and adolescents, treatment-naïve adults (≥18 years old), and previously treated adults. Furthermore, patients were classified into four mutually exclusive treatment groups, based on index medication: lisdexamfetamine (LDX), osmotic release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate long-acting (MPH LA), and amphetamine/dextroamphetamine long-acting (AMPH LA). The average daily consumption was measured as the quantity of index medication supplied in the 12-month study period divided by the total number of days of supply. Therapy augmentation was defined as the use of another ADHD medication concomitantly with the index medication for ≥28 consecutive days. Therapy augmentation and deviation rates from the recommended once-daily dosing regimen were compared between treatment groups using multivariate logistic regression models.. Compared to the other treatment groups, LDX patients were less likely to augment with another ADHD medication (range odds ratios [OR]; 1.28-3.30) and to deviate from the recommended once-daily dosing regimen (range OR; 1.73-4.55), except for previously treated adult patients, where therapy augmentation differences were not statistically significant when compared to OROS MPH and MPH LA patients.. This study did not control for ADHD severity.. Overall, compared to LDX-treated patients, patients initiated on other ADHD medications were equally or more likely to have a therapy augmentation and more likely to deviate from the recommended once-daily dosing regimen.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Insurance Claim Review; Lisdexamfetamine Dimesylate; Male; Retrospective Studies; United States; Young Adult

To compare treatment persistence in attention-deficit/hyperactivity disorder (ADHD) of patients initiated on lisdexamfetamine (LDX) vs other ADHD medications.. A large US administrative claims database was used to select ADHD patients who initiated an ADHD medication (index treatment) during/after 2007. Patients were classified, based on age and previous treatment status, as treatment-naïve or previously treated children and adolescents (6-17 years) and treatment-naïve or previously treated adults (18 years and older). Furthermore, patients were classified into seven mutually exclusive treatment groups, based on their index treatment: LDX, atomoxetine (ATX), osmotic-release methylphenidate hydrochloride long-acting (OROS MPH), other methylphenidate/dexmethylphenidate short-acting (MPH SA) and long-acting (MPH LA), and amphetamine/dextroamphetamine short acting (AMPH SA) and long-acting (AMPH LA). Treatment persistence, analyzed through discontinuation (interruption of the index treatment for ≥30 consecutive days), was compared between treatment groups using multivariate Cox proportional hazards. Patients were followed until first treatment discontinuation or up to 12 months after the initiation of the index treatment, whichever occurred first.. Among children and adolescents, LDX patients had a significantly lower discontinuation rate compared to other treatment groups (range hazard ratios [HRs]; 1.04-2.26; all p < 0.05), except when compared to treatment-naïve patients on ATX and OROS MPH, where no statistically significant differences were found and where LDX had a higher risk of discontinuation, respectively. Among adults, LDX patients had a significantly lower discontinuation rate compared to patients in other treatment groups (range HR; 1.14-1.86; all p < 0.05), except for the comparison with AMPH LA patients, where differences were not statistically significant.. This study did not control for ADHD severity.. LDX-treated patients were associated with higher persistence compared to patients initiated on other ADHD medications, except for the comparisons with OROS MPH and ATX treated patients in treatment-naïve children and adolescents and AMPH LA-treated patients in adults.

Topics: Adolescent; Adult; Age Factors; Amphetamines; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Comorbidity; Dextroamphetamine; Drug Combinations; Female; Humans; Insurance Claim Review; Lisdexamfetamine Dimesylate; Male; Medication Adherence; Retrospective Studies; United States; Young Adult

Attention deficit hyperactivity disorder (ADHD) is the commonest behavioural disorder in the UK, affecting 2-5% of school-aged children and young people.(1) Guidelines from the National Institute for Health and Care Excellence (NICE) state that medication is not indicated as first-line treatment for school-age children and young people with ADHD, but should be reserved for those with severe symptoms and impairment, or those with moderate levels of impairment who have refused non-drug interventions, or those whose symptoms have not responded sufficiently to parent-training/education programmes or group psychological treatment.(2) Current drug options include methylphenidate (first-line), atomoxetine (first- or second-line) or dexamfetamine (second- or third-line).(2) Lisdexamfetamine (Elvanse-Shire Pharmaceuticals) is a prodrug of dexamfetamine, licensed as part of a comprehensive treatment programme for ADHD in children aged 6 years and over when response to previous methylphenidate treatment is considered clinically inadequate.(3,4) Here we review the place of lisdexamfetamine in the management of ADHD in children and adolescents.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Practice Guidelines as Topic; Severity of Illness Index; United Kingdom

Due to concerns about the safety of stimulants for ADHD, novel assessments of the cardiopulmonary impact of these agents are needed.. An open design of lisdexamfetamine (LDX) in 15 adults with DSM-IV ADHD. Following a psychiatric evaluation and medical history, subjects underwent echocardiography (TTE) and cardiopulmonary exercise testing (CPET). LDX was titrated to 70 mg daily over 6 weeks, followed by monthly visits to 6 months. Change in TTE and CPET measures were examined following up to 6 months of LDX.. At endpoint, there were no significant alterations in indices of cardiac systolic performance, or in metabolic and ventilatory variables at maximum exertion (P values >0.05). We found significant mean changes in resting LV systolic dimension and Doppler diastolic indices. Change in heart rate recovery at 1 min met statistical significance (P = 0.05).. We did not detect clinically meaningful changes in cardiac structure and function or in metabolic and ventilatory variables at maximum exertion in ADHD adults receiving open LDX. The clinical significance of changes in resting LV dimension and indices of diastolic function are not in the direction of cardiomyopathy. Future large sample controlled study can examine these findings, as well as stimulants' impact on heart rate recovery.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Case-Control Studies; Central Nervous System Stimulants; Dextroamphetamine; Echocardiography; Exercise Test; Female; Heart; Heart Rate; Humans; Hypertension; Lisdexamfetamine Dimesylate; Male; Middle Aged; Prospective Studies

Fatigue is commonly reported in the primary care setting; however, its cause is often unclear. This article presents 3 cases involving patients with chronic fatigue syndrome who responded poorly to treatment. After clinical evaluation, all patients were found to meet criteria for attention-deficit/hyperactivity disorder (ADHD) and underwent a standard regimen of a psychostimulant medication. After treatment with psychostimulants, the 3 patients reported improved symptoms of fatigue and pain, and cognitive and core ADHD symptoms. These cases suggest that ADHD and chronic fatigue syndrome (and possibly fibromyalgia) share a common underlying mechanism. This article presents a model suggesting that over time, ADHD (predominantly inattentive type) develops into a syndrome of chronic fatigue and pain. These cases indicate that fatigue may be an important presenting symptom of adult ADHD. These cases also suggest the need for additional research to determine the prevalence of ADHD in patients who present with fatigue, and, in those meeting criteria for ADHD, the responsiveness of fatigue to psychostimulant treatment.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Dextroamphetamine; Fatigue Syndrome, Chronic; Female; Fibromyalgia; Humans; Lisdexamfetamine Dimesylate; Middle Aged; Treatment Outcome

Medication treatment studies of ADHD have typically not assessed effects on reading performance, although reading difficulties frequently co-occur in children with ADHD. The current study characterizes the effects of lisdexamfetamine dimesylate (LDX; Vyvanse(®), Shire US Inc.), at peak efficacy, on reading performance in children with ADHD.. Children (ages 6-12; N = 26) with ADHD enrolled in a modified laboratory school study with an open-label, dose-optimization phase of LDX (30-70 mg/d). The Gray Oral Reading Test-4 (GORT-4) with measures of rate, accuracy, and comprehension was administered at baseline and 3-4 hr postdose, following 4 to 5 weeks of optimal dose titration.. Treatment reduced ADHD symptoms. Reading rate was improved, especially among children with higher verbal fluid reasoning without additional symptoms of neurodevelopmental delay. No differences were observed for reading accuracy or comprehension.. Endophenotypical profiles may predict drug effects in specific skill areas, such as reading rate.

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Female; Humans; Lisdexamfetamine Dimesylate; Male; Reading; Single-Blind Method; Treatment Outcome

The brain reward system consists of extensive neural pathways that mediate reward behavior such as pleasure and motivation. These pathways may be involved in the development of symptoms such as apathy, anhedonia, and cognitive dysfunction seen in patients with major depression. These pathways are served primarily, although not exclusively, by the chemical neurotransmitter dopamine, which has suggested a therapeutic role for drugs that influence dopamine activity. A small number of clinical trials using various dopaminergic and stimulant drugs for the treatment of major depression and bipolar depression have demonstrated some benefit when combined with standard antidepressant drugs. Based on this work, several ongoing trials are investigating the use of the stimulant drug lisdexamfetamine (Vyvanse®) as an adjunctive treatment for depression.

Topics: Amphetamines; Antidepressive Agents; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Benzhydryl Compounds; Brain; Central Nervous System Stimulants; Depressive Disorder, Major; Dextroamphetamine; Dopamine; Dopamine Agents; Drug Therapy, Combination; Epinephrine; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Modafinil; Norepinephrine; Propylamines

To illustrate how claims data can be used to (1) develop outcome scores that predict response to a traditional treatment and (2) estimate the economic impact of individualized assignment to a newer treatment based on the outcome score. An example application is based on two treatments for attention deficit hyperactivity disorder (ADHD): osmotic-release oral system methylphenidate (OROS-MPH) and lisdexamfetamine dimesylate (LDX).. Adolescents with ADHD initiating OROS-MPH (n=6320) or LDX (n=6394) were selected from the MarketScan claims database. A model was developed for predicting risk of switching/augmentation with OROS-MPH using multiple baseline characteristics. The model was applied to an independent sample to stratify patients by their predicted risk and, within each stratum, risk of switching/augmentation and ADHD-related total costs were compared between OROS-MPH and LDX patients using inverse probability of treatment weighting.. The prediction model resulted in substantial stratification, showing risk of switching/augmentation with OROS-MPH ranging from 11.3-42.1%. In the two strata where OROS-MPH had highest risk of switching/augmentation, LDX had significantly lower risk of switching/augmentation than OROS-MPH (by 7.0-8.2%) and lower ADHD-related annual total costs (by $264-$625 per patient).. The current study has used the risk of switching/augmentation as a proxy measure for treatment efficacy to establish the prediction model. Future research using a clinical measure for ADHD symptoms is warranted to verify the findings.. Combining multiple patient characteristics into a predicted score for treatment outcomes with a traditional treatment can help identify subgroups of patients who benefit most from a new treatment. In this analysis, ADHD patients with a high predicted score for switching/augmentation with OROS-MPH had a lower rate of switching/augmentation with LDX. Assigning OROS-MPH and LDX treatments based on the predicted scores that are heterogeneous in a patient population may help improve clinical outcomes and the cost-effectiveness of care.

Topics: Adolescent; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Comparative Effectiveness Research; Costs and Cost Analysis; Dextroamphetamine; Female; Health Services; Humans; Insurance Claim Review; Lisdexamfetamine Dimesylate; Male; Methylphenidate; Models, Statistical

Psychostimulants (methylphenidate and amphetamines) are the drugs of first choice in the pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD).. We summarize the pharmacological characteristics of amphetamines and compare them with methylphenidate, special emphasis being given to a comparison of effects and side effects of the two substances. Finally, we analyze the abuse and addiction risks.. Publications were chosen based on a Medline analysis for controlled studies and meta-analyses published between 1980 and 2011; keywords were amphetamine, amphetamine salts, lisdexamphetamine, controlled studies, and metaanalyses.. Amphetamines generally exhibit some pharmacologic similarities with methylphenidate. However, besides inhibiting dopamine reuptake amphetamines also cause the release of monoamines. Moreover, plasma half-life is significantly prolonged. The clinical efficacy and tolerability of amphetamines is comparable to methylphenidate. Amphetamines can therefore be used if the individual response to methylphenidate or tolerability is insufficient before switching to a nonstimulant substance, thus improving the total response rate to psychostimulant treatment. Because of the high abuse potential of amphetamines, especially in adults, the prodrug lisdexamphetamine (Vyvanse) could become an effective treatment alternative. Available study data suggest a combination of high clinical effect size with a beneficial pharmacokinetic profile and a reduced abuse risk.. In addition to methylphenidate, amphetamines serve as important complements in the psychostimulant treatment of ADHD. Future studies should focus on a differential comparison of the two substances with regard to their effects on different core symptom constellations and the presence of various comorbidities.

Topics: Adolescent; Adult; Amphetamines; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Child; Controlled Clinical Trials as Topic; Dextroamphetamine; Half-Life; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Risk Factors; Substance-Related Disorders

Topics: Altitude Sickness; Amphetamine; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Humans; Hypertension, Pulmonary; Lisdexamfetamine Dimesylate; Male; Middle Aged

Throughout this decade, there has been significant research into pharmacotherapies for attention-deficit hyperactivity disorder (ADHD). This article considers the efficacy and safety of five of the more novel long-acting pharmacological treatments recently approved by the FDA for marketing in the US for paediatric ADHD, along with an alpha(2)-adrenoceptor agonist in preparation. Reviewed treatments include the non-stimulant atomoxetine, three novel extended-release (XR) stimulant preparations: dexmethylphenidate, lisdexamfetamine dimesylate and the methylphenidate transdermal system (TDS), and the recently approved XR alpha(2)-adrenoceptor agonist, guanfacine. Dexmethylphenidate XR is a stimulant treatment in a single isomer form, and has an efficacy and tolerability similar to two doses of immediate-release (IR) dexmethylphenidate when taken 4 hours apart, but is dosed at half of the usual d,l-methylphenidate dose. Dexmethylphenidate XR utilizes a beaded bimodal release, with 50% initially released and another 50% released 4 hours later to provide benefit lasting up to 10-12 hours. Lisdexamfetamine was the first stimulant treatment approved as a prodrug, whereby the single isomer d-amfetamine remains pharmacologically inactive until activated by cleaving the lysine. Its efficacy and tolerability are generally consistent with that of XR mixed amfetamine salts, with this activation method and more consistent absorption generally resulting in up to an 11- to 13-hour benefit. The methylphenidate TDS patch utilizes skin absorption to provide predictable and uniform delivery of methylphenidate when worn for 9 hours/day. The efficacy and tolerability of the methylphenidate TDS patch is generally consistent with that of osmotic-controlled release oral system (OROS) methylphenidate, providing benefit for about 11-12 hours. Because of their formulation, lisdexamfetamine and methylphenidate each have an onset of effect at about 2 hours after administration. An adjustable wear time for the methylphenidate TDS patch accommodates related adverse effects, but its disadvantages are frequent skin irritation and the need to remember to take the patch off. Atomoxetine is the first non-stimulant treatment approved by the FDA and employs weight-based dosing up to 1.4 mg/kg/day. Benefit is generally observed within 2-8 weeks of initiation and is considered to have a lesser therapeutic effect than that of stimulants. A recent parallel-group controlled study found that atomoxet

Topics: Administration, Oral; Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Child; Clonidine; Dexmethylphenidate Hydrochloride; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Approval; Drug Therapy, Combination; Half-Life; Health Care Costs; Humans; Lisdexamfetamine Dimesylate; Methylphenidate; Pediatrics; Prodrugs; Propylamines; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Treatment Outcome

To complete an exploratory uncontrolled study of the effects of lisdexamfetamine dimesylate (LDX) on growth of children treated for attention-deficit/hyperactivity disorder (ADHD).. Height, weight, and body mass index (BMI) from 281 children ages 6 to 13 years from longitudinal assessments up to 15 months were compared to norms from the Centers for Disease Control.. At study entry, children were taller and heavier than average. Growth delays were largest for weight and BMI, and there was a 13 percentile point decrease in height. Children continued to grow in terms of height while treated with LDX; we found no increase in raw weight or BMI during the study period. LDX treatment was significantly associated with diminished gains in height, weight, and BMI compared to levels that would be expected based on age-appropriate standards from the Centers for Disease Control. Growth delays were greatest for the heaviest and tallest children, for those who had not previously received stimulant therapy, and for those with a greater cumulative exposure to LDX. More work is needed to determine effects on ultimate adult height.. Consistent with prior studies of stimulants, treatment with LDX leads to statistically significant reductions in expected height, weight, and BMI. Growth of patients with ADHD treated with LDX should be closely monitored and corrective action taken should growth delays be observed.

Topics: Attention Deficit Disorder with Hyperactivity; Body Height; Body Mass Index; Body Weight; Central Nervous System Stimulants; Child; Clinical Trials, Phase III as Topic; Cross-Over Studies; Dextroamphetamine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Lisdexamfetamine Dimesylate; Male; Randomized Controlled Trials as Topic

Lisdexamfetamine dimesylate (LDX) is a prodrug stimulant approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults and children 6-12 years of age. Parent surveys provide valuable information regarding the impact of ADHD treatments.. Parents of children with ADHD beginning treatment with LDX voluntarily completed surveys through an automated telephone system or the Internet before and 6 weeks after LDX treatment initiation. Prescribing physicians received individual reports of the responses for each survey completed by their patients' parents. All patients whose parents completed both baseline and 6 week surveys were included in the analyses. Subgroup analyses were conducted for those previously treated with medications to treat ADHD, including mixed amphetamine salts-extended release.. LDX treatment was associated with a significant decrease in ADHD symptom interference with school activities, family interactions, homework, and social interactions (P<.01; N=11,576). Parents rated satisfaction with LDX as significantly higher than with their child's previous treatment (P<.01). On average, global improvement, tolerability, convenience, and satisfaction with LDX were all highly rated.. Patients treated with LDX showed significant symptom improvement and parents reported significantly greater satisfaction than with prior treatment.

Topics: Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Female; Health Surveys; Humans; Lisdexamfetamine Dimesylate; Male; Outcome Assessment, Health Care; Parents; Pediatrics; Severity of Illness Index; Surveys and Questionnaires

We describe here the case of an adolescent who developed eosinophilic hepatitis during treatment for attention-deficit/hyperactivity disorder with lisdexamfetamine dimesylate (Vyvanse [Shire US Inc, Wayne, PA]). A 14-year-old boy presented to his primary care provider with abdominal pain and worsening jaundice. A diagnosis of hepatitis was made with biochemical markers, but evaluation failed to provide an etiology. Worsening hepatitis prompted hospitalization and initiation of steroids for presumed autoimmune hepatitis. A subsequent liver biopsy showed evidence of eosinophilic hepatitis. Known causes of eosinophilic hepatitis were ruled out, and a presumptive diagnosis of reaction to lisdexamfetamine dimesylate was made. Discontinuation of the medication led to resolution of the hepatitis and normalization of the liver biopsy. To our knowledge, this is the first report of hepatic injury attributed to lisdexamfetamine dimesylate.

Topics: Adolescent; Alanine Transaminase; Aspartate Aminotransferases; Attention Deficit Disorder with Hyperactivity; Chemical and Drug Induced Liver Injury; Dextroamphetamine; Eosinophilia; Humans; Lisdexamfetamine Dimesylate; Male

Topics: Administration, Cutaneous; Adolescent; Atomoxetine Hydrochloride; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Delayed-Action Preparations; Dextroamphetamine; Drug Administration Schedule; Guanfacine; Humans; Lisdexamfetamine Dimesylate; Locus Coeruleus; Methylphenidate; Neurons; Nutrition Surveys; Prefrontal Cortex; Propylamines

Lisdexamfetamine dimesylate is a long-acting amfetamine prodrug that requires in vivo hydrolysis to gradually release active d-amfetamine. It is approved in the US for the treatment of attention-deficit hyperactivity disorder (ADHD) in adults and in children aged 6-12 years. In a study in adult stimulant abusers, oral lisdexamfetamine 50 or 100 mg showed less 'likability' response than immediate-release d-amfetamine 40 mg on the Drug Rating Questionnaire-Subject (DRQS) Liking scale. However, there was no significant difference between lisdexamfetamine 150 mg and d-amfetamine 40 mg. In a randomized, double-blind, phase III trial in adult patients with ADHD, oral lisdexamfetamine 30, 50 or 70 mg/day for 4 weeks caused a significantly greater improvement in ADHD-Rating Scale (ADHD-RS) total score than placebo; significant between-group differences favouring lisdexamfetamine were evident after 1 week. Lisdexamfetamine was generally well tolerated in adult patients with ADHD, with most treatment-emergent adverse events being of mild to moderate severity and consistent with the known effects of psychostimulants.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Clinical Trials, Phase III as Topic; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Lisdexamfetamine Dimesylate; Male; Surveys and Questionnaires; Young Adult

Topics: Amphetamine-Related Disorders; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate

Lisdexamfetamine dimesylate is the first long-acting prodrug stimulant and is indicated for the treatment of attention deficit/hyperactivity disorder. Lisdexamfetamine dimesylate is a therapeutically inactive molecule.. Following oral ingestion, it is converted to L-lysine and active d-amphetamine, which is responsible for the therapeutic effect. Lisdexamfetamine dimesylate was developed with the goal of providing a long duration of effect with the potential for less abuse-related liking.. In controlled clinical trials lisdexamfetamine dimesylate demonstrated a significant efficacy and extended duration of action as well as a safety profile consistent with other once-daily stimulants (mixed amphetamine salts extended release). In addition, abuse liability studies have shown that lisdexamfetamine dimesylate has lower abuse-related liking scores compared with equipotent doses of immediate-release d-amphetamine.

Topics: Adult; Attention Deficit Disorder with Hyperactivity; Child; Delayed-Action Preparations; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Prodrugs; Randomized Controlled Trials as Topic; Treatment Outcome

The human cytochrome P450 (P450) system is implicated in many drug interactions. Lisdexamfetamine dimesylate (NRP104), the proposed generic name for a new agent under investigation for treatment of attention deficit hyperactivity disorder, was recently analyzed for inhibitory drug-drug interactions with seven major P450 isoforms using pooled human liver microsomes. Probe substrates were used near the K(m) concentration values reported in the literature for CYP1A2 (phenacetin), CYP2A6 (coumarin), CYP2B6 (bupropion), CYP2C9 (tolbutamide), CYP2C19 ([S]-mephenytoin), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam and testosterone), and lisdexamfetamine was evaluated at concentrations ranging from 0.01 to 100 muM for its ability to inhibit the activity of these seven P450 isoforms. NADPH was added to one set of samples to initiate metabolic reactions, which were then terminated by adding organic solvent, vortexing the samples, and placing them on ice. The relevant substrates were then introduced to both sets of samples so that the percentage of remaining activity could be measured and compared. In addition, these samples were compared with other samples with the same concentrations of lisdexamfetamine but without preincubation. None of the seven P450 isoforms showed any concentration-dependent inhibition. Comparison of results from microsomes preincubated with and without NADPH showed no mechanism-based inhibition. Neither concentration-dependent nor mechanism-based inhibition caused by time-dependent inactivation of human P450 isoforms was shown for lisdexamfetamine during in vitro testing. The evidence suggests that lisdexamfetamine has a low potential for drug-drug interactions or initiation of drug-drug interactions.

Topics: Attention Deficit Disorder with Hyperactivity; Cytochrome P-450 Enzyme System; Dextroamphetamine; Drug Interactions; Humans; Lisdexamfetamine Dimesylate; Microsomes, Liver; NADP

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Child Behavior; Dextroamphetamine; Drug Labeling; Humans; Lisdexamfetamine Dimesylate; Treatment Outcome

Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Child; Dextroamphetamine; Dopamine; Drug Approval; Humans; Lisdexamfetamine Dimesylate; Norepinephrine; Prodrugs; Randomized Controlled Trials as Topic; Substance-Related Disorders; United States; United States Food and Drug Administration

Topics: Attention Deficit Disorder with Hyperactivity; Child; Dextroamphetamine; Drug Interactions; Humans; Lisdexamfetamine Dimesylate

Attention-deficit/hyperactivity disorder (ADHD) is known to be a strong risk factor for substance use disorders (SUD) in adolescence and in adulthood. Research shows that stimulant treatment does not increase the risk of SUD in adolescents or adults with ADHD but rather that stimulant treatments may have a protective effect. However, 2 in 10 youths with ADHD misuse their medication. Recent evidence suggests that slow uptake of medication in the brain allows for effective treatment without patients experiencing the euphoric qualities of immediate-release agents that lead to abuse or diversion. As a result, extended-release products and different formulations, such as lisdexamfetamine dimesylate (LDX), are less likely to be misused and diverted and may have lower abuse potential.

Topics: Adolescent; Adult; Attention Deficit Disorder with Hyperactivity; Brain; Central Nervous System Stimulants; Delayed-Action Preparations; Dextroamphetamine; Humans; Lisdexamfetamine Dimesylate; Psychotropic Drugs; Risk Factors; Substance-Related Disorders; Time Factors