Lisdexamfetamine dimesylate: A prodrug stimulant for the treatment of ADHD in children and adults

ABSTRACTAttention-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.</jats:p

Characteristics of ADHD symptom response/remission in a clinical trial of methylphenidate extended release

Clinical trials in attention-deficit/hyperactivity disorder (ADHD) have typically measured outcome using clinician ratings on the Attention-Deficit/Hyperactivity Disorder Rating Scale, Fourth Edition (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale. Remission has been defined as an endpoint score of less than or equal to 18 on the ADHD-RS-IV (or a mean score of 1). Responders have been defined as patients who achieve a CGI-I score of much or very much improved (1 or 2). There is a lack of agreement in the literature on what percent change in symptoms on the ADHD-RS-IV should be used to define improvement or remission. This study uses data from a clinical trial of a methylphenidate extended release (MPH-MLR; Aptensio XR&#174;) phase III clinical trial to attempt to determine the percent change of symptoms that best corresponds with improvement and remission. Symptom remission at endpoint (ADHD-RS-IV total score &#8804;18) was most closely aligned with a &#8805;46% reduction in ADHD-RS-IV total score. Clinical improvement was most closely aligned with a &#8805;40% reduction in ADHD-RS-IV total score. The three different measures of outcome were strongly aligned during double blind and open label treatment, and were independent of subtype status. Our data suggest that at least 40% improvement in symptoms is needed to achieve a robust response at endpoint

Effects of daily SKF 38393, quinpirole, and SCH 23390 treatments on locomotor activity and subsequent sensitivity to apomorphine

An article written by Bruce Mattingly and published in Spring 1993 issue of Psychopharmacology, pages 320-326

Individualization of attention-deficit/hyperactivity disorder treatment: Pharmacotherapy considerations by age and co-occurring conditions

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that manifests in childhood and can persist into adolescence and adulthood. Impairments associated with ADHD can impact quality of life, social interactions, and increase the risk of morbidity and mortality; however, for many patients, effective treatment can lessen these effects. Pharmacotherapy with stimulants or nonstimulants is recommended in conjunction with psychosocial therapy for most patients. Determining the optimal pharmacotherapy can be complex, and the clinician needs to consider many factors such as the patient\u27s age, comorbidities, and lifestyle. Furthermore, the needs of the patient with ADHD will change over time, with specific challenges to consider at each stage of life. A variety of Food and Drug Administration (FDA)-approved stimulant and nonstimulant formulations are available with different modes of delivery and durations of effect. This armamentarium of ADHD medications can be used to individualize ADHD treatment for each patient\u27s needs. This article combines current information from the literature and the first-hand experience of the authors to provide guidance on ADHD treatment options for patients of different ages and for some of the more common comorbidities

Understanding Autonomous Practice

What is autonomous practice? As one of the elements of Vision 2020, au­tonomous practice is one whose mean­ing may not always be readily under­stood. The confusion can stem from the meaning of autonomy, which is sometimes misinterpreted to mean that the physical therapist (PT) practices in a vacuum, without coordinating and com­municating with other health care pro­viders. Nothing could be further from the truth. In fact, many PTs might be surprised to learn that they already prac­tice autonomously

Long-term safety and effectiveness of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder

ABSTRACTObjective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).Methods: 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.Results: 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&lt;.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P&lt;.0001).Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.</jats:p

Serdexmethylphenidate/dexmethylphenidate effects on sleep in children with attention-deficit/hyperactivity disorder

IntroductionSleep-related problems are common in children with attention-deficit/hyperactivity disorder (ADHD). Sleep disorders are also side effects of all stimulant ADHD medications. Serdexmethylphenidate/dexmethylphenidate (SDX/d-MPH) is a once-daily treatment approved for patients age 6 years and older with ADHD. In this analysis, sleep behavior was assessed during SDX/d-MPH treatment in children with ADHD.MethodsIn a 12-month, dose-optimized, open-label safety study in 6- to 12-year-old participants (NCT03460652), a secondary endpoint was assessment of sleep behavior based on the Children’s Sleep Habits Questionnaire (CSHQ) consisting of 8 sleep domains (bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep-disordered breathing, and daytime sleepiness). This post hoc analysis examined the individual sleep domains in the 12-month safety study.ResultsOf 282 participants enrolled, 238 were included in the sleep analysis. At baseline, mean (SD) CSHQ total sleep disturbance score was 53.4 (5.9). After 1 month of treatment, the mean (SD) CSHQ total score significantly decreased to 50.5 (5.4); least-squares mean change from baseline was −2.9 (95% CI: −3.5 to −2.4; p &lt; 0.0001) and remained decreased up to 12 months. Mean sleep-score improvements from baseline to 12 months were statistically significant (p &lt; 0.0001) for 5 of 8 sleep domains, including bedtime resistance, sleep anxiety, night wakings, parasomnias, and daytime sleepiness. Parasomnias and daytime sleepiness sleep domains showed the greatest mean improvement from baseline to 12 months. Sleep onset delay and sleep duration scores increased from baseline to 12 months. No statistically significant worsening occurred from baseline in sleep duration and sleep-disordered breathing domains; however, worsening of sleep onset delay was statistically significant.ConclusionIn this analysis of children taking SDX/d-MPH for ADHD, sleep problems did not worsen based on the mean CSHQ total sleep disturbance score. Statistically significant improvements in most CSHQ sleep domains were observed after 1 month and lasted for up to 12 months of treatment