What are all the Attention Deficit Hyperactivity Disorder (ADHD) stimulants?

FDA-Approved ADHD Stimulant Medications

All FDA-approved ADHD stimulants fall into two main chemical classes: methylphenidate-based products and amphetamine-based products, both available in multiple short-acting and long-acting formulations. 1

Methylphenidate-Based Stimulants

Short-Acting Formulations (4-6 hours duration)

• Immediate-release methylphenidate (generic Ritalin) provides 4-6 hours of symptom control with onset at 30 minutes, requiring 2-3 daily doses 1, 2
• Peak plasma concentrations occur at 1-2 hours after dosing 2

Intermediate-Acting Formulations (6-8 hours duration)

• Older sustained-release methylphenidate formulations provide only 4-6 hours of clinical action despite being marketed as "sustained-release," with delayed onset and lower peak concentrations 1, 2
• Ritalin LA and similar newer intermediate formulations provide approximately 8 hours of coverage 2

Long-Acting Formulations (8-12 hours duration)

• OROS-methylphenidate (Concerta) provides the longest duration at 12 hours using an osmotic pump delivery system, making it superior for full school/work day coverage 1, 2
• Newer extended-release methylphenidate formulations with early peak followed by 8-12 hours of action are superior to older sustained-release products 2
• Microbead capsule formulations can be sprinkled for patients unable to swallow tablets 2

Amphetamine-Based Stimulants

Short-Acting Formulations (4-6 hours duration)

• Immediate-release amphetamine salts (generic Adderall) require 2-3 times daily dosing with 4-6 hour duration 3, 4
• Dextroamphetamine immediate-release (Dexedrine) has similar 4-6 hour duration 5

Long-Acting Formulations (8-14 hours duration)

• Extended-release mixed amphetamine salts (Adderall XR) provide approximately 8-9 hours of symptom control 5, 3
• Dextroamphetamine extended-release (Dexedrine Spansules) typically provides 8-9 hours of coverage 5
• Lisdexamfetamine (Vyvanse) is an amphetamine prodrug providing 13-14 hours of once-daily coverage, the longest duration among amphetamines 5

Key Clinical Distinctions Between Stimulant Classes

Efficacy and Response Patterns

• Both methylphenidate and amphetamine demonstrate equivalent overall efficacy with large effect sizes (approximately 1.0) for reducing ADHD core symptoms 1, 5
• Individual response is idiosyncratic: approximately 40% respond to both classes, 40% respond to only one class, making sequential trials essential 1
• Combined response rate approaches 80-90% when both stimulant classes are tried sequentially 5
• ADHD subtype does not predict response to specific stimulant class 1

Formulation Advantages

• Long-acting formulations are strongly preferred over immediate-release due to better medication adherence, lower rebound effects, and elimination of in-school dosing stigma 1, 2, 5
• Plasma concentration troughs with short-acting stimulants occur at unstructured times, which long-acting formulations prevent 2

Age-Specific Considerations

• For preschool-aged children (4-5 years): Methylphenidate is the recommended first-line stimulant despite amphetamine having FDA approval for children under 6 years, due to stronger evidence in this age group 5
• For adults: Amphetamine-based stimulants are preferred based on comparative efficacy studies 5

Common Adverse Effects (Both Stimulant Classes)

• Appetite loss, abdominal pain, headaches, and sleep disturbance are the most common short-term adverse effects 1
• Growth velocity decreases by 1-2 cm with persistent stimulant use, particularly at higher doses, though effects diminish by third year of treatment 1
• Small increases in blood pressure and pulse require regular monitoring 5
• Methylphenidate causes significantly less sleep disruption compared to amphetamines 2
• Hallucinations and psychotic symptoms occur uncommonly 1
• Sudden cardiac death in children on stimulant medication is extremely rare, with conflicting evidence on whether stimulants increase this risk 1

Critical Treatment Algorithm

1. Start with either methylphenidate or amphetamine as first-line treatment (methylphenidate for preschoolers, amphetamine preferred for adults) 5
2. Prioritize long-acting formulations over immediate-release for better adherence and consistent symptom control 2, 5
3. If first stimulant class fails, switch to the alternative stimulant class (amphetamine to methylphenidate or vice versa) before considering non-stimulants 5
4. For breakthrough symptoms, immediate-release formulations of the same stimulant class can be added at 30-50% of the total daily extended-release dose 5

Common Pitfalls to Avoid

• Do not assume lack of response to one stimulant class means failure of all stimulants; always trial the alternative class before abandoning stimulants 5
• Do not use older sustained-release formulations expecting full-day coverage when they only provide 4-6 hours 2
• Do not prescribe short-acting doses after 5-6 PM as this interferes with sleep onset 5
• In preschool-aged children, only prescribe medication for moderate-to-severe dysfunction persisting ≥9 months after behavioral interventions have failed 1