What is the recommended approach for a patient with Attention Deficit Hyperactivity Disorder (ADHD) when considering Mydayis (Mixed Salts of a Single-entity Amphetamine Product) versus Adderall XR (Dextroamphetamine and Amphetamine)

Mydayis vs. Adderall XR for ADHD Treatment

Direct Recommendation

For adults with ADHD requiring all-day symptom coverage extending into the evening, Mydayis (SHP465 mixed amphetamine salts) provides superior duration of action (up to 16 hours) compared to Adderall XR (12 hours), making it the preferred choice when extended coverage is needed. 1

However, both medications contain the same 3:1 ratio of dextroamphetamine to levoamphetamine and share identical efficacy profiles for core ADHD symptoms during overlapping coverage periods. 1

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Key Pharmacological Differences

Duration of Action

• Adderall XR delivers 12 hours of symptom control with a biphasic release mechanism: immediate-release pellets provide the first half of the dose upon ingestion, and delayed-release pellets release approximately 4 hours later. 1
• Mydayis extends coverage to 16 hours through a triple-bead delivery system, specifically designed to address late afternoon and evening functional impairment that Adderall XR may not adequately cover. 2

Onset of Action

• Both formulations demonstrate rapid onset within 1.5 hours of administration, making them equally suitable for morning symptom control. 1

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Clinical Decision Algorithm

Choose Mydayis When:

• Evening symptom coverage is essential for homework completion, social activities, or work responsibilities extending beyond typical school/work hours. 3
• The patient reports symptom breakthrough in late afternoon/evening despite optimized Adderall XR dosing. 3
• Once-daily extended coverage is needed to improve medication adherence in patients with executive dysfunction. 4

Choose Adderall XR When:

• Standard 12-hour coverage adequately addresses the patient's functional impairment across all settings. 1
• The patient experiences sleep disturbances that might worsen with longer-acting formulations. 3
• Cost considerations are significant, as Adderall XR has been available longer and may have more affordable generic options. 1

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Dosing Considerations

Adderall XR Protocol

• Start at 10 mg once daily in the morning, titrating by 5 mg weekly increments based on response and tolerability. 3
• Maximum recommended dose is 50 mg daily for adults, though some patients may require up to 0.9 mg/kg or 65 mg with clear documentation of inadequate response to lower doses. 3
• The average effective dose in controlled trials was 54 mg daily (administered as 30 mg twice daily in immediate-release studies, equivalent to extended-release formulations). 5

Mydayis Protocol

• Approved doses for adults are 12.5 mg, 25 mg, 37.5 mg, and 50 mg once daily in the morning. 6
• Doses below 12.5 mg (such as 6.25 mg) are subtherapeutic and should not be used, as demonstrated by lack of efficacy versus placebo in pediatric trials. 6
• Titration follows the same weekly increment approach as Adderall XR, with careful monitoring for extended-day side effects. 3

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Efficacy Evidence

Adderall XR

• 70-80% response rate in adults with ADHD when properly titrated. 4
• 42% reduction in ADHD Rating Scale scores versus placebo (p<.001) in controlled trials. 5
• 70% of patients achieved ≥30% symptom improvement compared to 7% with placebo (p=.001). 5

Mydayis

• Shares the same active ingredients and mechanism as Adderall XR, with equivalent efficacy during overlapping coverage hours. 1
• The primary advantage is extended duration rather than superior peak efficacy. 2

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Critical Safety Considerations

Shared Contraindications (Both Medications)

• Symptomatic cardiovascular disease including uncontrolled hypertension, coronary artery disease, and tachyarrhythmias. 3, 7
• Active substance use disorders require close supervision; consider long-acting formulations with lower diversion potential or non-stimulant alternatives. 3
• Concurrent MAOI use is absolutely contraindicated due to risk of hypertensive crisis. 7

Monitoring Requirements

• Baseline and regular cardiovascular assessment: blood pressure, pulse, and screening for symptomatic heart disease before initiation. 3
• Monthly follow-up visits until symptoms stabilize, using standardized rating scales to objectively measure improvement. 3
• Sleep and appetite monitoring is particularly important with Mydayis due to extended duration potentially affecting evening appetite and sleep onset. 3

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Common Pitfalls to Avoid

With Adderall XR

• Do not assume 12-hour coverage is inadequate without proper dose optimization—many patients reporting evening breakthrough are simply underdosed. 3
• Avoid starting at excessively high doses (>10 mg), as this increases adverse effects and reduces adherence. 3
• Do not add afternoon immediate-release doses without first maximizing the extended-release formulation, as this increases complexity and reduces adherence. 3

With Mydayis

• Do not prescribe doses below 12.5 mg, as these are subtherapeutic and will not provide adequate symptom control. 6
• Carefully assess sleep patterns before prescribing, as the 16-hour duration may interfere with sleep onset if dosed too late in the morning. 2
• Monitor for extended-day appetite suppression, which may be more pronounced than with 12-hour formulations. 7

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Special Clinical Scenarios

Comorbid Anxiety

• Anxiety does not contraindicate either medication but requires careful monitoring, as stimulants can precipitate acute anxiety in vulnerable individuals (38% in one study). 8
• Start at lower doses (5 mg Adderall XR equivalent) and titrate more slowly in patients with comorbid anxiety disorders. 8

Substance Use History

• Both formulations have lower abuse potential than immediate-release preparations due to extended-release mechanisms. 3
• Mydayis may offer additional diversion resistance due to its triple-bead formulation, though specific comparative data are limited. 2

Evening Functional Impairment

• Mydayis is specifically designed for patients requiring symptom control during evening homework, social activities, or work responsibilities. 2
• If Adderall XR is already prescribed and evening symptoms persist, increase the dose before switching to Mydayis, as many patients are simply underdosed. 3

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Treatment Algorithm Summary

1. Initiate Adderall XR 10 mg once daily for most adults with ADHD requiring once-daily dosing. 3
2. Titrate by 5 mg weekly until optimal response (typically 20-40 mg daily). 3
3. If evening breakthrough occurs despite adequate daytime coverage, consider switching to Mydayis at equivalent dosing. 2
4. If sleep disturbances emerge with Mydayis, consider returning to Adderall XR with strategic afternoon immediate-release supplementation. 3
5. If both formulations fail, trial methylphenidate-based alternatives before considering non-stimulants. 3