Can Vyvanse (lisdexamfetamine) and Adderall LR (mixed amphetamine salts extended‑release) be combined?

Combining Vyvanse and Adderall XR: Not Recommended

Combining Vyvanse (lisdexamfetamine) and Adderall XR (mixed amphetamine salts extended-release) is not recommended because both are amphetamine-based stimulants that would result in excessive total amphetamine dosing, increased cardiovascular risk, and amplified side effects without additional therapeutic benefit. 1

Why This Combination Is Problematic

Same Mechanism of Action

• Both Vyvanse and Adderall XR are amphetamine-based stimulants that work through identical mechanisms—they increase dopamine and norepinephrine in the brain 2, 3
• Lisdexamfetamine (Vyvanse) is a prodrug that converts to dextroamphetamine after oral ingestion through enzymatic hydrolysis in the blood 4
• Adderall XR contains mixed amphetamine salts (75% dextroamphetamine and 25% levoamphetamine) 5
• Combining them would simply add more amphetamine to your system rather than providing a different therapeutic approach 3

Dosing Ceiling and Safety Concerns

• The maximum recommended daily dose for amphetamine-based stimulants in adults is 50 mg for Adderall XR, with some clinical practice extending to 60-65 mg only when lower doses are documented as insufficient 1, 4
• Vyvanse maximum dose is 70 mg daily, which converts to approximately 30-40 mg of dextroamphetamine equivalent 4
• Taking both medications would exceed safe amphetamine exposure limits and dramatically increase cardiovascular risks including hypertension, tachycardia, and potential cerebrovascular events 1, 6

Amplified Adverse Effects

• Common stimulant side effects—decreased appetite, insomnia, headache, increased blood pressure and pulse, irritability, and anxiety—would be magnified with dual therapy 6, 7
• The risk of serious adverse events including psychotic symptoms, seizures (particularly at higher doses), and cardiovascular complications increases substantially with excessive amphetamine dosing 2, 3
• Withdrawal due to adverse events is already 2.69 times higher with amphetamines versus placebo at standard doses 3

What to Do Instead: Optimize Single-Agent Therapy

If Current Vyvanse Dose Is Inadequate

• Ensure you are taking the maximum therapeutic dose of Vyvanse (70 mg daily) before considering any changes 1, 3
• Vyvanse provides 12-hour symptom coverage; if symptoms return in the evening, adding a small immediate-release dextroamphetamine "booster" (5 mg) in late afternoon is the appropriate strategy—not adding Adderall XR 1, 5
• Approximately 70-80% of adults achieve optimal response when stimulants are properly titrated to maximum tolerated doses 1, 3

If Switching Between Amphetamine Formulations

• If Vyvanse 70 mg is not providing adequate coverage, switching to Adderall XR 30-40 mg once daily is appropriate, but you should discontinue Vyvanse first 4
• No washout period is required when switching between amphetamine formulations because they share the same active metabolite 4
• Monitor blood pressure and pulse at baseline and each visit during any dose adjustment 1, 6

If Single Stimulant Class Fails

• Approximately 40% of patients respond to both methylphenidate and amphetamine classes, while another 40% respond to only one class 1
• If amphetamine-based stimulants (Vyvanse or Adderall) are inadequate after proper titration, switch to methylphenidate-based stimulants (Concerta, Focalin) rather than combining amphetamines 1, 3

If Residual Symptoms Persist Despite Optimized Stimulant

• Add adjunctive guanfacine extended-release (1-4 mg daily) or clonidine, which are FDA-approved for combination with stimulants and work through different mechanisms (alpha-2 agonists) 1
• Consider adding atomoxetine (60-100 mg daily) for "around-the-clock" coverage if evening/morning symptoms are problematic, though this requires 6-12 weeks to reach full effect 1
• If comorbid depression or anxiety persists after ADHD improvement, add an SSRI (not another stimulant) 1

Critical Safety Monitoring

Cardiovascular Parameters

• Measure blood pressure and pulse at baseline and every visit during stimulant therapy 1, 6, 7
• Amphetamines are contraindicated in symptomatic cardiovascular disease, uncontrolled hypertension, hyperthyroidism, and glaucoma 1

Absolute Contraindications to Any Amphetamine Combination

• Never combine amphetamines with MAO inhibitors—requires 14-day washout after MAOI discontinuation due to hypertensive crisis risk 1
• Active psychosis or mania is an absolute contraindication to stimulant use 1
• Prior hypersensitivity to amphetamines precludes their use 1

Bottom Line

The correct approach when a single amphetamine-based stimulant is insufficient is to optimize that agent to maximum dose, add a non-amphetamine adjunctive medication (guanfacine, atomoxetine), or switch to a different stimulant class (methylphenidate)—never combine two amphetamine formulations. 1, 3