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Summary

Developmental impact of attention-deficit/hyperactivity disorder (ADHD): preschool children — presenting symptoms often include behavioral disturbances, aggression, or acting out; school age — additional concerns include academic difficulties, difficulties in peer relationships, and self-esteem issues; high school — self-esteem issues continue; additional issues include drug abuse and smoking; risk-taking behavior can lead to injuries; potential for criminal behavior and legal problems; college age and adulthood — academic difficulties, job and occupational issues, and increased risk of motor vehicle accidents and injuries

ADHD developmental trends by age: impulsivity and hyperactivity decrease with age; inattention remains steady or may worsen in adulthood and becomes more prevalent with age; rates of comorbidity increase

Medications for ADHD: nonstimulant medications may be used as monotherapy or as adjuncts; stimulant medications are the most common first-line treatment; effect size ≈1 for stimulants compared with ≈0.7 for atomoxetine and α agonists; methylphenidate and amphetamine are the core stimulants used for treatment of ADHD; comparable efficacy; ≈40% preferably respond to one of these, ≈40% respond to both, and 20% may not respond at all or have an adverse effect; subtype of ADHD is not a predictor of response to a specific agent; bupropion (Wellbutrin) and tricyclic antidepressants have lower efficacy

Mechanism of action: primary action of stimulants is to increase the synaptic availability of dopamine and norepinephrine; methylphenidate and amphetamine inhibit dopamine and norepinephrine transport or reuptake; unlike methylphenidate, amphetamine is transported into the presynaptic cell and displaces dopamine and norepinephrine from intracellular storage

Pharmacokinetics: onset of action ≈30 to 45 min; duration of action ≈3 to 4 hr for methylphenidate and ≈4 to 6 hr for amphetamine; both are racemic mixture; l-amphetamine is the therapeutically active isomer; d-amphetamine has a greater impact on dopamine and l-amphetamine on norepinephrine; d-methylphenidate is the therapeutically active isomer; variations in activity of different formulations are related to difference in delivery and mixtures of isomers

Methylphenidate oral formulation: available as oral solution and chewable tablet; both are bioequivalent to Ritalin immediate release (IR) methylphenidate formulation; both are racemic mixtures of d- and l-methylphenidate

Methylphenidate (Adhansia XR): approved for children aged ≥6 yr; mixture of d and l particles; biphasic release; 20% immediate release (IR) and 80% extended release (XR); first peak at ≈1.5 hr; second peak at ≈10 hr; effect lasts ≈12 to 14 hr; starting dose 25 mg; can be increased 10 to 15 mg/wk; disproportionate increase of certain side effects (eg, insomnia, decreased appetite) occurs at doses ≥70 mg in pediatric patients; should be consumed immediately if sprinkled on food

Methylphenidate (Aptensio XR): composed of composite multilayered beads, 30% IR and 70% XR; rapid initial release followed by a drop during lunchtime, then a second controlled release; levels gradually decrease into the evening; response comparable to other XR formulations; onset of action 1 to 1.5 hr; manufacturer reports effects last for ≈12 hr; other source suggests duration of 7 to 8 hr; starting dose 10 mg; can be increased 10 mg/wk

Methylphenidate (Contempla XR): orally disintegrating tablet (ODT); approved for children aged 6 to 17 yr; equal racemic mixture; 30% IR and 70% XR; starting dose 17.3 mg; speaker starts with 8.6 mg for younger children or children naïve to stimulants; significant clinical response lasts 8 to 12 hr; high-fat meals can decrease peak concentration and bioavailability; maximum dose 51.8 mg

Methylphenidate (QuilliChew ER): 30% IR and 70% XR; starting dose 10 mg; food delays time to peak concentration; effect lasts ≈8 hr with gradual loss between 8 and 10 hr

Methylphenidate (Quillivant XR): liquid; 30% IR and 70% XR; IR onset of action ≈45 min; gradual XR lasts ≈8 hr; loss of effect between 8 to 12 hr; recommended starting dose 20 mg for children aged ≥6 yr; consider 10 mg for young children

Methylphenidate (Jornay PM): dl-methylphenidate is the generic form; first evening dose stimulant medication; administered at bedtime; onset of action starts the following morning, ≈8 to 10 hr post-ingestion, followed by a period of XR through the day; starting dose 20 mg; can be increased 20 mg/wk; recommended time of dose 8 PM; speaker states timing can be adjusted from 6:30 to 9:30 PM; does not interfere with sleep onset; can cause early morning awakening

Methylphenidate (Daytrana): transdermal patch; onset of action ≈2 hr after application; total dose depends on the size of the patch and total time of application; recommended time for application ≤9 hr; absorption continues for ≈2 to 3 hr after removal; contact dermatitis is a frequent side effect; treated with cortisone cream; recommended to place on hip and alternate sides; avoid skin contact with the active surface after removal; ensure proper disposal

Amphetamine: newer IR formulations are Evekeo, Procentra, and Zenzedi; XR formulations are also available

Evekeo: 50% racemic mixture; approved for use in children aged ≥3 yr; recommended to give on awakening with 1 to 2 additional doses at 4 to 6 hr intervals; recommended starting dose for children aged 3 to 5 yr 2.5 mg; can increase 2.5 mg/wk; recommended starting dose for children aged ≥6 yr 5 mg; can increase 5 mg/wk

Procentra: IR dextroamphetamine oral solution; contains 5 mg of d-amphetamine in each 5 ml

Zenzedi: short-acting; must be administered 2 or 3 times daily; starting dose for children aged 3 to 5 yr 2.5 mg; can increase 2.5 mg/wk; starting dose for children aged ≥6 yr 5 mg; can increase 5 mg/wk; maximum dose 40 mg

Amphetamine (Adzenys XR): available as an ODT and oral solution; peak concentration between 5 and 6 hr; starting dose 6.3 mg; can increase in increments of 3.1 or 6.3 mg; maximum dose 18.8 mg for children aged 6 to 12 yr and 12.5 mg for ≥13 yr; ODT should not be crushed or chewed; must be taken consistently with or without food; administration with high-fat meals can decrease and delay peak plasma levels

Switching between different amphetamine products: can directly switch from Adderall XR to Adzenys ER; when switching, discontinue the first drug and start the second drug at the recommended starting dose for the child’s age

Amphetamine (Dynavel XR): liquid; initial rapid absorption; levels peak at 4 to 5 hr; duration ≤13 hr; causes less appetite suppression than other formulations; starting dose 2.5 or 5 mg in children aged ≥6 yr; increase by 2.5 to 10 mg/day every 4 to 7 days; speaker recommends increments of ≈2.5 mg in a younger child and 5 mg in an older child; maximum dose 20 mg/day

Amphetamine (Mydayis): duration ≤16 hr; gradual release and steady concentration because of 3 small release spurts; approved for children aged ≥13 yr; starting dose 12.5 mg for children aged ≥13 yr and 25 mg for adults with weekly dose adjustments

Lisdexamfetamine (Vyvanse): only prodrug stimulant; the pharmacologically inactive parent molecule is hydrolyzed in red blood cells after absorption, liberating the pharmacologically active d-amphetamine, causing delayed onset of action of ≈1.5 hr; reported duration ≈13 hr; starting dose 30 mg in children aged ≥6 yr; speaker prefers to start at 10 or 20 mg; can increase 10 to 20 mg/wk; also available as chewable tablet

ADHD mediation guide: available at www.ADHDmedicationguide.com

Endeavour: video game approved by the Food and Drug Administration for children aged 8 to 12 yr with ADHD; activates parts of the brain that control attention; Kollins et al (2020) showed that participants demonstrated improvement in attention; no serious adverse events; common adverse events included frustration, headache, dizziness, emotional reaction, and aggression

Omega-3 fatty acids: level 1 evidence indicates they can reduce symptoms by ≈20%; recommended dose 1 to 2 g/day with ≥400 mg of eicosapentaenoic acid

Saffron vs methylphenidate for ADHD (Baziar et al [2019]): participants receiving methylphenidate responded more quickly, but response rates were equal at 6 wk

Audience question about how to progress with various formulations: speaker prefers to start with generic medications; considers newer formulations if generic products do not work or if requested by the parent