Abstract
BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. Stimulants (methylphenidate [MPH] and amphetamine) are considered first-line ADHD pharmacotherapy. MPH is a catecholamine reuptake inhibitor, whereas amphetamines have additional presynaptic activity. Although MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many still fail to respond optimally to either. After administration, the prodrug stimulant lisdexamfetamine dimesylate (LDX) is converted to l-lysine and therapeutically active d-amphetamine in the blood. The objective of this study was to evaluate the clinical efficacy of LDX in children with ADHD who remained symptomatic (ie, nonremitters; ADHD Rating Scale IV [ADHD-RS-IV] total score > 18) on MPH therapy prior to enrollment in a 4-week placebo-controlled LDX trial, compared with the overall population.MethodsIn this post hoc analysis of data from a multicenter, randomized, double-blind, forced-dose titration study, we evaluated the clinical efficacy of LDX in children aged 6-12 years with and without prior MPH treatment at screening. ADHD symptoms were assessed using the ADHD-RS-IV scale, Conners' Parent Rating Scale-Revised short form (CPRS-R), and Clinical Global Impressions-Improvement scale, at screening, baseline, and endpoint. ADHD-RS-IV total and CPRS-R ADHD Index scores were summarized as mean (SD). Clinical response for the subgroup analysis was defined as a ≥ 30% reduction from baseline in ADHD-RS-IV score and a CGI-I score of 1 or 2. Dunnett test was used to compare change from baseline in all groups. Number needed to treat to achieve one clinical responder or one symptomatic remitter was calculated as the reciprocal of the difference in their proportions on active treatment and placebo at endpoint.ResultsOf 290 randomized participants enrolled, 28 received MPH therapy at screening, of which 26 remained symptomatic (ADHD-RS-IV > 18). ADHD-RS-IV total scores, changes from baseline, clinical responsiveness, and rates of symptomatic remission in this subgroup were comparable to the overall population. The safety and tolerability profiles for LDX were comparable to other stimulants currently available.ConclusionIn this analysis, children with significant clinical ADHD symptoms despite MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study population.Trial RegistrationClinicalTrials.gov: NCT00556296
Highlights
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurobehavioral psychiatric disorders that afflicts children [1], with a reported prevalence of 2.4% to 19.8% worldwide [2] using the criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) from the American Psychiatric Association [3]
Participant Demographics and Disposition In total, 297 children were enrolled at 40 study sites in the United States, of which 7 children discontinued prior to randomization, and 290 were randomized to receive lisdexamfetamine dimesylate (LDX) (n = 218) or placebo (n = 72)
Summary
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral psychiatric disorder that afflicts children, with a reported prevalence of 2.4% to 19.8% worldwide. The stimulant types most commonly used in ADHD treatment are methylphenidate (MPH) and amphetamine These have similar subjective effects [8] yet differ in their mechanisms of action–MPH is a dopamine and norepinephrine reuptake inhibitor, while amphetamines have additional presynaptic activity–stimulating the release of dopamine, norepinephrine, and serotonin [9]. Both are considered efficacious, a meta-analysis of 23 studies comparing the efficacy of immediate-release (IR) formulations of MPH and amphetamine in the treatment of children with ADHD revealed small but statistically significant differences in favor of amphetamine [10]. MPH and amphetamine can effectively manage ADHD symptoms in most pediatric patients, many patients still fail to respond optimally to either
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