Drug Update · Psychiatry

serdexmethylphenidate (AZSTARYS): SKAMP-Combined -5.4 vs Placebo in Pediatric ADHD Study 1

July 14, 2026

Primary efficacy (Study 1)

SKAMP-Combined placebo-subtracted difference -5.4 (-7.1, -3.7)

Pediatric study population

150 pediatric patients 6 to 12 years

Pilot adult study enrollment

17 enrolled, 15 included in analyses

Clinical Perspective

This report is directly relevant to clinicians treating pediatric and adolescent patients with ADHD, including child psychiatrists, pediatricians, and primary care clinicians who prescribe stimulant pharmacotherapy, because AZSTARYS is an FDA-indicated, once-daily serdexmethylphenidate/dexmethylphenidate product for patients 6 years and older ^[5]. The Study 1 data support that AZSTARYS reduced SKAMP-Combined scores across a 13-hour classroom day versus placebo, showing improvement in classroom-measured attention and behavior over that period ^[5]. How AZSTARYS compares directly with other methylphenidate formulations for daylong symptom control and for eliminating midday rebound in routine clinical practice is not reported in the provided source excerpts?

Dr. Mohit Joshi · Psychiatry

AZSTARYS (serdexmethylphenidate/dexmethylphenidate) is approved for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older. The randomized, double-blind Study 1 showed a placebo-subtracted least-squares mean change in SKAMP-Combined score of -5.4 (95% CI -7.1 to -3.7) averaged across a 13-hour classroom day ^[5].

Clinical Context

AZSTARYS is a combined serdexmethylphenidate/dexmethylphenidate formulation described in the prescribing information as containing a prodrug (serdexmethylphenidate) of dexmethylphenidate; dexmethylphenidate HCl is a central nervous system (CNS) stimulant ^[5]. The FDA label indicates AZSTARYS is indicated for ADHD in patients 6 years and older and that use in children younger than 6 years is not recommended because of higher plasma exposure and higher incidence of adverse reactions at equivalent dosing ^[5]. A separate pilot adult study of SDX/d-MPH reported substantial effects on investigator- and self-report symptom scores and time-sensitive measures throughout the day and reported the treatment was generally well tolerated in the study population included in that report ^[1].

Key Findings

The pediatric randomized, double-blind, placebo-controlled Study 1 (analog classroom) showed AZSTARYS produced a placebo-subtracted least-squares mean difference in SKAMP-Combined score of -5.4 (95% CI -7.1 to -3.7) averaged across the 13-hour classroom test day, assessed at 0.5, 1, 2, 4, 8, 10, 12, and 13 hours post-dose ^[5].
In Study 1, AZSTARYS was evaluated after an open-label dose-optimization period and then in a 1-week parallel-group randomized treatment period in pediatric patients 6 to 12 years of age; the SKAMP-Combined mean baseline score was 17.9 in both groups and the least-squares mean change from baseline was -4.87 (SE 0.62) for AZSTARYS versus 0.54 (SE 0.70) for placebo, yielding the placebo-subtracted difference of -5.4 (95% CI -7.1 to -3.7) ^[5].
A separate 6-week pilot adult study of SDX/d-MPH reported clinically meaningful effects across investigator-rated (AISRS), self-report (ASRS), time-sensitive ADHD (TASS) scores, impairment (CGI), executive function (BRIEF-A), and medication smoothness (AMSES); that pilot enrolled 17 adults with DSM-5 ADHD, with 15 included in the analyses after 2 discontinuations during observation and one additional dropout early in open-label treatment ^[1].

Safety & Tolerability

Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease treated with CNS stimulants; AZSTARYS labeling recommends assessing for presence of cardiac disease prior to treatment ^[5]^[2].
CNS stimulants cause increases in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 beats per minute); monitor blood pressure and pulse ^[2]^[3].
Psychiatric adverse reactions have been reported, including new psychotic or manic symptoms and exacerbation of preexisting psychosis or induction of a manic episode in patients with bipolar disorder ^[2]^[3].
Priapism (prolonged and painful erections) has been reported with methylphenidate products and has been described in the labeling ^[2]^[3].
Peripheral vasculopathy, including Raynaud’s phenomenon, has been reported with stimulants used to treat ADHD ^[2]^[3].
Long-term suppression of growth (height and weight) in pediatric patients has been associated with CNS stimulants in pediatric populations and is described in the labeling ^[2]^[3].
Increased intraocular pressure and reports of angle closure glaucoma have been noted with methylphenidate-containing products ^[2].
Motor and verbal tics and worsening of Tourette’s syndrome have been reported; evaluate family history and monitor for emergence or worsening of tics ^[2]^[3].
Common adverse reactions listed for dexmethylphenidate-containing products in the provided DailyMed excerpts include abdominal pain, fever, nausea, anorexia, dyspepsia, decreased appetite, headache, anxiety, dry mouth, and pharyngolaryngeal pain ^[2]^[3]^[4].

Study Design

Study 1 (pediatric classroom study) was a randomized, double-blind, placebo-controlled, parallel-group analog classroom study enrolling 150 pediatric patients 6 to 12 years of age with DSM-5 ADHD; subjects underwent an open-label dose-optimization period followed by randomization to individually optimized AZSTARYS dose (mean dose 45.6 mg/9.0 mg reported for the study population) or placebo for a 1-week parallel-group treatment period, with SKAMP assessments at 0.5, 1, 2, 4, 8, 10, 12, and 13 hours post-dose on the classroom test day ^[5]. Clinicians should consult current prescribing information for full dosing guidance. The pediatric Study 1 results reported a mean baseline SKAMP-Combined score of 17.9 and a placebo-subtracted LS mean change of -5.4 (95% CI -7.1 to -3.7) averaged across the test day ^[5]. A separate 6-week pilot adult open-label study enrolled 17 adults, with 15 included in analyses, and reported substantial effects on multiple clinician- and patient-reported measures throughout the day; full pilot study details are in the PubMed summary ^[1].

FAQ

Q1 What is AZSTARYS approved for?

AZSTARYS (serdexmethylphenidate/dexmethylphenidate) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older. The labeling specifies that use in pediatric patients younger than 6 years is not recommended because they had higher plasma exposure and a higher incidence of adverse reactions at the same dosage.

Q2 How does AZSTARYS work?

Serdexmethylphenidate in AZSTARYS is described in the prescribing information as a prodrug of dexmethylphenidate; dexmethylphenidate HCl is a central nervous system stimulant. The label states the prodrug is converted to active dexmethylphenidate and that dexmethylphenidate is the CNS-active component, although the precise therapeutic mode of action in ADHD is not known.

Q3 What is the recommended dose of AZSTARYS?

For pediatric patients 6 to 12 years the recommended starting dosage is 39.2 mg serdexmethylphenidate/7.8 mg dexmethylphenidate once daily in the morning; the dosage may be increased after one week to 52.3 mg/10.4 mg or decreased to 26.1 mg/5.2 mg per day depending on response and tolerability, with a maximum recommended dosage of 52.3 mg/10.4 mg once daily. For adults and pediatric patients 13 to 17 years the recommended starting dosage is 39.2 mg/7.8 mg once daily with increase after one week to 52.3 mg/10.4 mg per day depending on response and tolerability. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the most common side effects of AZSTARYS and related dexmethylphenidate products?

The provided labeling and product information for dexmethylphenidate-containing products list adverse reactions and warnings that include increases in blood pressure and heart rate, psychiatric adverse reactions (including new psychotic or manic symptoms), priapism, peripheral vasculopathy including Raynaud’s phenomenon, long-term suppression of growth in pediatric patients, increased intraocular pressure and reports of angle closure glaucoma, and motor and verbal tics. Common reported adverse reactions in pediatric populations for methylphenidate-containing products in the excerpts include abdominal pain, fever, nausea, anorexia, dyspepsia, decreased appetite, headache, anxiety, dry mouth, and pharyngolaryngeal pain. The AZSTARYS label advises pretreatment screening for cardiac disease and evaluation for tics or Tourette’s syndrome, and monitoring for blood pressure, pulse, growth in children, and psychiatric symptoms during treatment.

serdexmethylphenidate (AZSTARYS): SKAMP-Combined -5.4 vs Placebo in Pediatric ADHD Study 1

serdexmethylphenidate (AZSTARYS): SKAMP-Combined -5.4 vs Placebo in Pediatric ADHD Study 1

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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