lisdexamfetamine-dimesylate and Sleep-Initiation-and-Maintenance-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

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

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

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