What distinguishes Zenzedi (dextroamphetamine) from other Attention Deficit Hyperactivity Disorder (ADHD) medications?

Zenzedi (Dextroamphetamine) Compared to Other ADHD Medications

Zenzedi (dextroamphetamine sulfate) is a pure dextroamphetamine stimulant medication that differs from other ADHD medications primarily in its chemical composition, potency, and duration of action, making it particularly effective for patients who require more targeted dopaminergic effects compared to mixed amphetamine salts or methylphenidate-based alternatives.

Pharmacological Properties of Zenzedi

Zenzedi is a branded formulation of dextroamphetamine sulfate, which has specific characteristics that distinguish it from other ADHD medications:

• Pure Dextroamphetamine: Unlike mixed amphetamine salts (like Adderall) which contain both dextroamphetamine and levoamphetamine, Zenzedi contains only the dextro-isomer, which is considered the more potent form for treating ADHD symptoms 1

• Mechanism of Action: Acts primarily as a substrate for the dopamine transporter (DAT) with less effect on norepinephrine (NET) and serotonin transporters compared to some other stimulants 2

• FDA Indication: Specifically indicated for ADHD in children ages 3-16 years, making it one of the few stimulants approved for very young children 1

Comparison with Other ADHD Medications

Versus Other Stimulants

1. Compared to Mixed Amphetamine Salts (Adderall):

   • Zenzedi contains only dextroamphetamine, while Adderall contains a 3:1 ratio of dextro to levoamphetamine
   • May produce fewer peripheral side effects due to absence of levoamphetamine
   • Maximum daily dose is 50 mg, similar to mixed amphetamine salts 3

2. Compared to Methylphenidate (Ritalin, Concerta):

   • Different mechanism of action: dextroamphetamine promotes dopamine release while methylphenidate primarily blocks reuptake
   • Typically considered more potent on a milligram-per-milligram basis than methylphenidate
   • Methylphenidate is often recommended as first-line treatment for children and adolescents 3

3. Compared to Lisdexamfetamine (Vyvanse):

   • Lisdexamfetamine is a prodrug of dextroamphetamine that requires enzymatic conversion
   • Zenzedi has a more immediate onset but shorter duration compared to Vyvanse
   • Lisdexamfetamine has lower abuse potential due to its prodrug formulation 4

4. Compared to Dextroamphetamine Transdermal System:

   • The transdermal system offers flexible wear times and is beneficial for patients who cannot take oral medications
   • Oral Zenzedi provides more immediate onset of action
   • The transdermal system has unique skin-related side effects to consider 5, 6

Versus Non-Stimulants

1. Compared to Atomoxetine (Strattera):

   • Zenzedi acts primarily on dopamine, while atomoxetine is a selective norepinephrine reuptake inhibitor
   • Zenzedi has a more rapid onset of action (within hours vs. weeks for atomoxetine)
   • Atomoxetine may be preferred for patients with substance abuse concerns 2

2. Compared to Alpha-2 Agonists (Guanfacine/Clonidine):

   • Zenzedi directly affects dopaminergic pathways, while alpha-2 agonists work through noradrenergic mechanisms
   • Alpha-2 agonists have less potential for abuse and may cause less insomnia
   • Alpha-2 agonists are often used as adjunctive therapy with stimulants 4

Clinical Considerations

Efficacy Profile

• Studies comparing dextroamphetamine to other medications like modafinil have shown that dextroamphetamine produces significant improvements in ADHD symptoms 7
• Pure dextroamphetamine may provide more targeted effects on attention and executive function with potentially fewer peripheral effects

Safety and Side Effect Profile

• Common side effects include decreased appetite, sleep disturbances, and cardiovascular effects (increased heart rate and blood pressure)
• Contraindications include advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, and hyperthyroidism 3
• Requires careful monitoring of vital signs, weight, and appetite, with follow-up 1-2 weeks after starting medication 3

Special Populations

1. Preschool Children (3-5 years):

   • One of the few stimulants FDA-approved for children as young as 3 years
   • Should be used cautiously with lower starting doses and smaller increments when increasing 4

2. Adolescents:

   • Requires monitoring for potential diversion or misuse
   • May need coverage for symptom control while driving 4

Practical Prescribing Considerations

• Dosing: Start with lower doses and titrate gradually based on response and tolerability
• Administration: Can be taken with or without food; timing may affect sleep patterns
• Monitoring: Regular assessment of vital signs, growth parameters, and potential side effects is essential
• Drug Holidays: May be considered to assess continued need and reduce potential side effects 3

Pitfalls and Caveats

• Higher abuse potential compared to prodrugs or non-stimulant options
• May not be suitable for patients with history of substance abuse
• Requires careful monitoring for cardiovascular effects
• Potential for growth suppression with long-term use requires regular height and weight monitoring

Zenzedi represents an important option in the ADHD medication arsenal, particularly for patients who may benefit from pure dextroamphetamine rather than mixed formulations or different mechanisms of action.