Efficacy and Safety of Lisdexamfetamine in Preschool Children With Attention-Deficit/Hyperactivity Disorder
Ann C Childress1, Eric Lloyd2, Leslie Jacobsen3
1Center for Psychiatry and Behavioral Medicine, Las Vegas, Nevada.
Insights
Lisdexamfetamine dimesylate (LDX) effectively reduced symptoms of attention-deficit/hyperactivity disorder (ADHD) in preschoolers. This ADHD medication was generally well-tolerated, with no new safety concerns identified in this age group.
Area of Science:
- Pediatric Psychiatry
- Neurodevelopmental Disorders
- Pharmacology
Background:
- Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder affecting children.
- Preschool-aged children with ADHD often present unique challenges in symptom management and treatment efficacy.
- Lisdexamfetamine dimesylate (LDX) is an established treatment for ADHD in older populations, but its use in younger children requires specific evaluation.
Purpose of the Study:
- To assess the acute efficacy of lisdexamfetamine dimesylate (LDX) compared to placebo (PBO) in treating ADHD symptoms in preschool-aged children (4-5 years).
- To evaluate the safety and tolerability profile of LDX in this specific pediatric population.
- To determine the optimal dosage range for LDX in young children with ADHD.
Main Methods:
- A phase 3, double-blind, randomized, fixed-dose study involving 199 children aged 4-5 years diagnosed with ADHD.
- Participants received LDX (5, 10, 20, or 30 mg) or PBO for 6 weeks.
- Efficacy was measured by the change in ADHD Rating Scale IV, Preschool version, total score (ADHD-RS-IV-PS-TS) and Clinical Global Impression-Improvement (CGI-I) scores. Safety was monitored through adverse events and vital signs.
Main Results:
- LDX demonstrated statistically significant improvement in ADHD-RS-IV-PS-TS compared to PBO (LS mean difference: -5.9, p=0.0242).
- A greater proportion of children on LDX showed improvement on CGI-I scores (41.7% vs 24.3% for PBO, p=0.0857; LS mean difference: -0.6, p=0.0074).
- Treatment-emergent adverse events (TEAEs) were slightly higher with LDX (46.6%) versus PBO (42.2%), with decreased appetite and irritability being most common. Discontinuations due to TEAEs were low (5.5% for LDX).
Conclusions:
- Lisdexamfetamine dimesylate (LDX) is an effective treatment for reducing ADHD symptoms in preschool-aged children (4-5 years).
- The observed effect size for symptom reduction in this age group was smaller than in older children and adolescents.
- LDX was generally well-tolerated in this population, and no new safety signals were identified, supporting its use in this age group.
Objective:
To evaluate the acute efficacy, safety, and tolerability of lisdexamfetamine dimesylate (LDX) vs placebo (PBO) in preschool-aged children with attention-deficit/hyperactivity disorder (ADHD).
Method:
This phase 3, double-blind, fixed-dose study randomly assigned children (aged 4-5 years) with ADHD to 6 weeks of LDX (5, 10, 20, 30 mg) or PBO. The prespecified primary (change from baseline at week 6 in ADHD Rating Scale IV, Preschool version, total score [ADHD-RS-IV-PS-TS]) and key secondary (Clinical Global Impression-Improvement [CGI-I] score at week 6) efficacy endpoints were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments included treatment-emergent adverse events (TEAEs) and changes in pulse and blood pressure (BP).
Results:
The study comprised 199 participants randomly asigned 5:5:5:5:6 to receive 5, 10, 20, 30 mg LDX or PBO, respectively. Least squares (LS) mean (95% CI) treatment difference at week 6 between pooled LDX (10, 20, 30 mg) and PBO was statistically significant for ADHD-RS-IV-PS-TS change (-5.9 [-11.01, -0.78], p = .0242; effect size [ES], -0.43). CGI-I scores improved (ie, 1-2 on CGI-I) in 41.7% for pooled LDX and 24.3% for PBO (p = .0857). The LS mean (95% CI) treatment difference between pooled LDX and PBO for CGI-I score at week 6 was -0.6 (-1.03, -0.16; p = .0074; ES, -0.52). Frequency of TEAEs was 46.6% across all 4 LDX doses vs 42.2% with PBO; the most frequent TEAEs were decreased appetite (13.7% vs 8.9%, respectively) and irritability (9.6% vs 0%). Discontinuations because of TEAEs were 5.5% for all LDX doses and 4.4% for PBO. Mean ± SD pulse/BP changes from baseline at week 6/early termination were numerically greater with LDX vs PBO (pulse beats/min: 2.7 ± 10.79 vs 1.2 ± 9.90; systolic BP, mm Hg: 1.0 ± 7.51 vs 0.3 ± 6.06; diastolic BP, mm Hg: 1.7 ± 5.90 vs 0.0 ± 6.88).
Conclusion:
In children aged 4 to 5 years with ADHD, LDX was more efficacious than PBO in reducing symptoms. The observed ES for change in ADHD-RS-IV-PS-TS appears to be smaller in magnitude than has been reported for studies of LDX conducted in older children and adolescents. LDX was generally well tolerated, and no new safety signals were identified.
Clinical Trial Registration Information:
Safety and Efficacy Study in Preschool Children Aged 4-5 Years With Attention-Deficit/Hyperactivity Disorder; http://www.
Clinicaltrials:
gov; NCT03260205.
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