What are some extended release (ER) or sustained release (SR) medications, such as Concerta (methylphenidate) or Adderall XR (amphetamine and dextroamphetamine), for treating Attention Deficit Hyperactivity Disorder (ADHD) in children and adults?

Extended-Release and Sustained-Release ADHD Medications

Long-acting stimulant formulations are the preferred first-line pharmacological treatment for ADHD, with multiple methylphenidate and amphetamine extended-release options available that provide 8-12 hours of symptom control with once-daily morning dosing. 1

Methylphenidate Extended-Release Formulations

Osmotic-Release System

• Concerta (OROS-MPH) uses an osmotic pump delivery system that produces an ascending plasma drug level pattern and provides up to 12 hours of symptom control with once-daily morning dosing 1, 2
• Concerta has been shown equally effective as methylphenidate immediate-release tablets given 3 times daily in double-blind, placebo-controlled trials 1
• The 18-mg Concerta dose is equivalent to methylphenidate 5 mg three times daily 1

Microbead Technology (8-Hour Duration)

• Metadate CD and Ritalin LA utilize microbead technology for extended release, providing approximately 8 hours of symptom control 2
• These formulations use a combination of immediate-release and delayed-release beads to achieve bimodal drug delivery 1

Dexmethylphenidate Extended-Release

• Focalin XR (dexmethylphenidate extended-release) consists of only the active d-enantiomer of methylphenidate and uses spheroidal oral drug absorption system (SODAS) technology 3, 4
• Provides 50% immediate medication delivery and 50% delayed release approximately 4 hours after ingestion, mimicking two doses of immediate-release dexmethylphenidate given 4 hours apart 4
• Demonstrates efficacy for up to 12 hours after dosing in analog classroom studies 3, 4
• Available in doses of 5-30 mg/day for children and adolescents, and 20-40 mg/day for adults 4

Evening-Dosed Formulation

• Delayed-release/extended-release methylphenidate (DR/ER-MPH) is the first long-acting stimulant taken in the evening, with clinical effects delayed until awakening in the morning 5
• This represents a paradigm shift from traditional morning-dosed stimulants 5

Older Sustained-Release Formulations (Less Preferred)

• Ritalin-SR (MPH-SR20) uses a wax-matrix vehicle for slow release but is less effective than immediate-release methylphenidate due to delayed onset (90 minutes vs. 30 minutes), lower peak plasma levels, and peak benefit occurring at 3 hours rather than 2 hours 1
• Generic sustained-release methylphenidate products (Methylphenidate-SR, Metadate, Methylin-SR) use the same wax-matrix mechanism as Ritalin-SR 1
• These older formulations have far less clinical use than expected due to reduced efficacy compared to immediate-release preparations 1

Amphetamine Extended-Release Formulations

Mixed Amphetamine Salts

• Adderall XR contains mixed amphetamine salts in an extended-release formulation using controlled-release technology 1
• Provides symptom control through a combination of immediate-release and delayed-release beads 1

Prodrug Formulation

• Lisdexamfetamine dimesylate (Vyvanse) is a prodrug that requires enzymatic conversion to active dextroamphetamine, providing extended duration of action 1
• Approved as first-line therapy in the United States but as second-line therapy in many European countries 1

Older Formulation

• Dexedrine Spansules (DEX Spansules) are capsules containing small medication particles for sustained release, providing effects on vigilance tests for up to 9 hours 1

Key Advantages of Long-Acting Formulations

• Better medication adherence compared to multiple daily doses of immediate-release stimulants 1
• Lower risk of rebound effects with sustained plasma levels 1
• Eliminates need for in-school dosing, avoiding school administration issues, peer ridicule, and privacy concerns particularly important for adolescents 1
• Consistent symptom coverage during unstructured times (lunchtime, recess, bus rides) when immediate-release formulations typically reach plasma level troughs 1
• Improved coverage for after-school activities, including homework, sports, driving (for adolescents), and social interactions 1

Alternative Delivery Systems

• Transdermal patches are available for methylphenidate, providing an alternative route of administration 1
• Chewable tablets and liquid formulations have been developed for patients who have difficulty swallowing capsules 1

Critical Considerations When Selecting Formulations

• Pharmacokinetic profiles differ between long-acting formulations, particularly regarding rate of peak attainment and decline, which should guide selection based on the patient's symptom profile and daily schedule needs 1
• Duration of coverage needed varies by patient—some require 8-hour coverage for school only, while others need 12-hour coverage for homework, driving, and evening activities 6, 2
• For preschool-aged children (4-5 years), methylphenidate is the recommended first-line stimulant despite amphetamine having FDA approval for children under 6 years 6
• For adults, amphetamine-based stimulants are preferred based on comparative efficacy studies 6, 7

Common Pitfall to Avoid

• Do not assume all extended-release formulations are equivalent—older wax-matrix sustained-release preparations (Ritalin-SR, generic methylphenidate-SR) are significantly less effective than newer delivery systems (Concerta, Metadate CD, Ritalin LA, Focalin XR) and should generally be avoided 1