TABLE 2.

Summary of the included trials.

Nct number	Study title	Objectives	Interventions	Primary outcome measures	Secondary outcome measures	Phases	Allocation	Intervention model	Masking	Enrollment	Duration (days)	Locations
NCT01711021	Study to Evaluate Safety and Efficacy of d-Amphetamine Transdermal System vs. Placebo in Children and Adolescents With ADHD	Evaluate the safety and efficacy of d-Amphetamine Transdermal System in treating ADHD in children and adolescents	d-Amphetamine Transdermal System	Assessment of classroom behavior, focusing on attention (SKAMP-A), deportment (SKAMP-D), and work quality through thirteen specific items, measured pre-dose to 12 h post-dose	Alteration in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) score’s onset and duration of effect: a 13-item scale assessing classroom behavior. Significant efficacy difference observed between d-ATS and placebo 2 hours post-dose, sustained for up to 12 h (p < 0.001)	Phase 2	Randomized	Crossover	Triple	106	151	United States
NCT03610464	Pharmacokinetic Study of DYANAVEL XR (Amphetamine) Extended-release Oral Suspension, in Children Aged 4–5 Years	Study the plasma concentration of amphetamine extended-release oral suspension in 4-5-year-old children with ADHD after a 2.5 mg dose	Amphetamine Extended-Release Suspension [Dyanavel]	Post-dose plasma concentrations of d- and L-amphetamine were measured at specific time intervals ranging from 0 to 28 h	N/A	Phase 4	NA	Single group	None	5	16	United States
NCT00151996	Safety and Tolerability of SPD503 and Psychostimulants in Children and Adolescents Aged 6–17 With attention deficit hyperactivity disorder (ADHD)	Assess the safety of combining SPD503 with psychostimulants for ADHD treatment in children and adolescents aged 6–17	Methylphenidate + SPD503 (Guanfacine hydrochloride) and Amphetamine + SPD503	Using the ADHD Rating Scale-fourth edition (ADHD-RS-IV), a change in the total score was evaluated over 6 weeks. The scale consisted of eighteen items with a scoring range from 0 (absent symptoms) to 54 (severe symptoms)	Improvements noted on CGI-I, CPRS-R, and PGA scores, and CHQ-PF50 increased at 6 weeks, representing enhanced ADHD management and wellbeing. CGI-I and PGA improvements were defined by scores of 1 or 2	Phase 2	Non-randomized	Parallel	None	75	133	N/A
NCT00393042	Sleep and Tolerability Study: Comparing the Effects of Adderall XR and Focalin XR	Compare ADHD treatment responses, sleep effects, and side effects between Adderall XRآ® and Focalin XRآ® in children and adolescents	Dexmethylphenidate and Mixed Amphetamine Salts, ER	Participants’ sleep patterns over 8 weeks were tracked using Actigraphs (AW64 series) in their home settings. Bed and wake times were recorded via sleep logs, and activity data discerned sleep from wakefulness. The impacts of medications like Adderall XR and Focalin XR on sleep were also assessed	ADHD Rating Scale-IV and CGI-S used over 8–10 weeks showed severity of ADHD symptoms and the effects of DAT 1 gene variations. WFIRS indicates functional impairment in children with ADHD.	Phase 3	Randomized	Crossover	Quadruple	77	1,127	United States
NCT01740206	Should Chronic Stimulant Medications be Continued Preoperatively in Patients with Attention Deficit Hyperactivity Disorder (ADHD)	Examine the effects of administering or withholding stimulant medication on surgery day in ADHD patients, assessing blood pressure, heart rate, and medication use	Amphetamine and/or methylphenidate and hold stimulant medication	Heart rate measurement was taken prior to anesthetic induction on Day 1	Pre-anesthetic induction blood pressure measurements were taken. Anxiety was assessed via mYPAS in patients with and without midazolam prior to anesthesia. Higher mYPAS scores signify greater anxiety	N/A	Non-randomized	Single group	None	50	1,125	United States
NCT01986062	Crossover Study to Evaluate the Efficacy of AR11 in Pediatric Patients with ADHD in a Laboratory Classroom Setting	Evaluate ADHD symptom changes in pediatric patients (6–12 years) treated with AR11 or placebo using SKAMP and PERMP assessments	AR11	The SKAMP-combined score, derived from thirteen items with a scoring range of 0 (normal) to 78 (maximum impairment), assessed ADHD symptoms in a laboratory classroom setting, with measurements taken 2 h post-dose	SKAMP-Combined and Subscales assessed ADHD symptoms with 0–6 scales, with higher scores indicating greater impairment. PERMP evaluates ADHD using a 400-question math test, analyzing attempts and accuracy	Phase 4	Randomized	Crossover	Quadruple	97	151	United States
NCT00506727	Analog Classroom Study Comparison of ADDERALL XR With STRATTERA in Children Aged 6–12 With ADHD	Compare ADDERALL XR and STRATTERA’s effects using the SKAMP deportment scale	Mixed amphetamine salts (ADDERALL XR) and Atomoxetine hydrochloride	The change in SKAMP deportment scores from baseline to endpoint was determined over an average of 3 weeks, specifically on Days 7, 14, and 21	After approximately 3 weeks, treatment-emergent adverse events were assessed using PERMP, SKAMP attention scale, CGI, CGIS-P, and Peds QL.	Phase 4	Randomized	Parallel	Double	215	332	United States
NCT02083783	TRI102 in the Treatment of Children with Attention Deficit Hyperactivity Disorder (ADHD)	Determine TRI102’s effectiveness for ADHD treatment in children aged 6–12	TRI102	A change from the baseline in the SKAMP-Combined score, ranging from 0 (normal) to 78 (maximum impairment), was measured approximately 4 h post-dose	PERMP is a math test that evaluated effortful performance and correct answers. The primary efficacy measure was the pre- and post-dose comparison at predetermined timepoints, specifically 4 h after medication intake	Phase 3	Randomized	Parallel	Quadruple	108	275	United States
NCT00507065	Safety and Efficacy of ADDERALL XR in the Treatment of Adolescents Aged 13–17 With Attention Deficit Hyperactivity Disorder (ADHD)	Evaluate ADDERALL XR’s safety and efficacy versus placebo in adolescents (age 13–17) with ADHD, considering weight	Mixed salts of a single-entity amphetamine (ADDERALL XR)	Within the cohort weighing ≤75 kg, the change in the ADHD-RS-IV score from the baseline to the conclusion of the study’s double-blind phase was gauged over roughly 4 weeks	Changes in ADHD-RS-IV scores and CGI for ADHD were evaluated from baseline to the double-blind phase’s final visit over approximately 4 weeks. Concurrently, adverse events, labs, physical exams, and ECG results were assessed	Phase 3	Randomized	Parallel	Double	329	301	United States
NCT00889915	Comparing the Effectiveness of New Versus Older Treatments for Attention Deficit Hyperactivity Disorder (The NOTA Study)	Compare the efficacy and tolerability of new versus old psychostimulant ADHD medications	Methylphenidate transdermal system, Lisdexamfetamine dimesylate, Osmotic-release oral system methylphenidate (OROS MPH) and Mixed amphetamine salts extended release	Categorizing participants using CGI-E Scale as Responders or Non-responders, based on drug effectiveness and side effects, with scores averaged by week 6	CGI-I and CGI-A scales assessed the improvement and medication acceptability respectively at the participant’s last study visit (latest at Week 6) using a 7-point scale. Both contribute to the primary endpoint (CGI-E)	Phase 4	Randomized	Parallel	None	228	244	United States
NCT03327402	Safety, Tolerability and Pharmacokinetics of SHP465 in Children Aged 4–5 Years with attention deficit hyperactivity disorder (ADHD)	Study the PK, safety, and tolerability of multiple daily 6.25 mg doses of SHP465 in 4-5-year-old children with ADHD.	SHP465	Plasma concentrations of d-Amphetamine and l-Amphetamine were evaluated using rich sampling collection for metrics including Cmax, Tmax, Ctrough, AUC, Lambda z, CL/F, t1/2, and Vss/F during specified times. Vital signs, ECG, height, weight, and laboratory results were monitored. Sleep was assessed using PSQ and CSHQ, and suicidal ideation through C-SSRS during the study, noting that the values may not reflect actual precision	Plasma concentrations of d-amphetamine and l-amphetamine were assessed at 12-, 16-, and 24-h post-dose using a detailed sampling method in Week 4. The area under the concentration-time curve (AUC) for these substances was evaluated between 5 and 12, 12–16, and 16–24 h post-dose	Phase 1	NA	Single group	None	24	206	United States
NCT00557011	NRP104, Adderall XR or Placebo in Children Aged 6–12 Years With ADHD	Assess NRP104 and Adderall XR’s efficacy and safety compared to placebo in 6–12-year-old children with ADHD.	NRP104 and Adderall XR	Assessed SKAMP-DS scores over a week-long treatment evaluation period	At 1 week, the SKAMP Attention Scale, PERMP attempted score, PERMP correct score, and CGI scores were evaluated, alongside treatment emergent adverse events and the PK profile and PK/PD relationship of NRP104 after multiple doses	Phase 2	Randomized	Crossover	Quadruple	52	91	N/A
NCT01133847	Interventions for Children with Attention and Reading Disorders	Compare attention and reading outcomes in children with ADHD and RD under three treatments: ADHD-only, RD-only, and combined treatments	Methylphenidate, Mixed Salt Amphetamine, Atomoxetine and Guanfacine	The SNAP assesses ADHD symptoms in children through parent and teacher ratings on a four-point Likert scale, showing robust reliability. The WIAT-III measures academic achievement with standardized scores. Both were evaluated post 16-week treatment and at follow-up	Post 16-week treatment, evaluations included WIAT-III, DIBELS ORF, TOWRE, and TOSREC, measuring reading comprehension, oral and silent fluency, and word efficiency	Phase 4	Randomized	Parallel	Single	222	1,673	United States
NCT03088267	Dyanavelآ® XR Extended-Release Oral Suspension in the Treatment of Children With ADHD: A Laboratory School Study	Assess DYANAVEL XR’s efficacy and safety for ADHD treatment in children aged 6–12	Amphetamine extended-release oral suspension, 2.5 mg/mL extended-release oral suspension	Assessing ADHD-related classroom impairment, the SKAMP-C scale measures academic tasks, rule adherence, and social interactions. A decrease from baseline to 30 min post-dose indicates improvement with treatment	The PERMP-C Score, assessing academic productivity in school children, was evaluated for changes from pre-dose at 30 min and at 3 h post-dose. A numerical increase indicated an improvement	Phase 3	Randomized	Crossover	Double	18	261	United States
NCT01886469	A Phase II, Adaptive Trial Design Examining the Pharmacokinetic and Pharmacodynamic Effects of Modified Release Amphetamine (HLD100, Formulations B, C and E)) in Adolescents and Children with attention deficit hyperactivity disorder (ADHD)	Study HLD100s absorption rates in adolescents and children with ADHD.	HLD100-B, HLD100-C, and HLD100-E	Measuring d-amphetamine’s absorption rate and extent using AUC0-tz, AUC0-∞, Cmax, Tmax, absorption lag time, λz, and t1/2elim over a 48-h period	Safety aspects, including adverse events, ECG, lab parameters, and physical examinations, were assessed within a 48-h timeframe	Phase 1 & Phase 2	Non-randomized	Parallel	None	22	62	Canada
NCT00228046	Medication Strategies for Treating Aggressive Behavior in Youth with Attention Deficit Hyperactivity Disorder	Examine the effectiveness of combining divalproex sodium with stimulants to reduce aggression in ADHD children	Divalproex Sodium, Methylphenidate, Dextroamphetamine, and Mixed Amphetamine Salts	After 8 weeks of treatment, aggression was assessed using the Overt Aggression Scale, and ADHD symptom improvement was gauged via the Clinical Global Improvement Scale and ADHD Rating Scale	N/A	Phase 4	Randomized	Parallel	Double	40	1,277	United States
NCT00712699	Effectiveness of an Extended-Release Stimulant Medication in Treating Preschool Children With ADHD	Evaluate extended-release mixed amphetamine salts in preschool ADHD treatment	Sequence 1: XR-MAS then placebo. Sequence 2: Placebo then XR-MAS	Weekly assessment for 6 weeks on the Composite Parent and Teacher Conners Rating Scale Score and tolerance of extended-release mixed amphetamine salts	The Clinical Global Impression-Improvement Score was assessed weekly over a 6-week period	N/A	Randomized	Crossover	Triple	27	791	N/A
NCT02578030	Pharmacokinetic Study in Children and Adolescents Aged 6–17 Years Who Have Been Diagnosed With ADHD	Profile the pharmacokinetics of SHP465 in children and adolescents aged 6–17 with ADHD.	SHP465 12.5 mg and SHP465 25 mg	Outcome measures assessed Cmax, Tmax, AUC0-infinity, AUClast, t½, CL/F, and Vz/F for both d-amphetamine and l-amphetamine in plasma at specified post-dose intervals	Post-treatment adverse events, including symptoms, disease, vital sign changes, ECG, lab test anomalies, and C-SSRS-measured suicidal behaviors or ideation, were observed for up to 72 h post-dose	Phase 1	Non-randomized	Single group	None	27	17	United States
NCT02204410	Omega-3 Supplementation to ADHD Medication in Children	Assess Omega-3 fatty acids’ effectiveness for DESR in ADHD children and adolescents aged 6–17 currently on ADHD medication	Omega-3 Fatty Acid and ADHD Medication	The Emotional Control Subscale of the BRIEF-Parent, assessing a child’s emotional response modulation, and the CGI Improvement for Deficient Emotional Self-Regulation, a clinician-rated 7-point scale, both evaluated at baseline and 12 weeks	N/A	Phase 4	NA	Single group	None	21	762	United States