What is the best treatment approach for a patient with Attention Deficit Hyperactivity Disorder (ADHD) who is taking Adderall (amphetamine and dextroamphetamine) 35mg and Strattera (atomoxetine) 40mg, but still experiences inadequate control of symptoms throughout the day?

Optimizing ADHD Treatment for Inadequate Full-Day Coverage

Your patient requires dose optimization of the current stimulant (Adderall 35mg) before adding or switching medications, as the current dose is below the maximum recommended range and the Strattera dose is subtherapeutic. 1, 2

Immediate Optimization Strategy

Step 1: Optimize Stimulant Dosing First

Increase Adderall (mixed amphetamine salts) to 40-50 mg daily, as the maximum recommended dose is 50 mg/day for adults, and your patient is currently at 35 mg—well below the therapeutic ceiling. 1, 2 The evidence shows that underdosing is the most common pitfall in ADHD management, and titration should continue to optimal effect rather than stopping at arbitrary dose limits. 1

• Titrate in 5-10 mg increments weekly based on response and tolerability, monitoring both therapeutic effects and adverse events at each adjustment. 1, 2
• The current 35 mg dose suggests room for further optimization before declaring stimulant failure. 1

Step 2: Optimize Atomoxetine Dosing Concurrently

Increase Strattera (atomoxetine) from 40 mg to 80-100 mg daily, as the current dose is at the starting level and far below the maximum recommended dose of 100 mg/day or 1.4 mg/kg/day. 3, 4

• Titrate by 20 mg increments every 7-14 days to reach 60 mg, then 80 mg, and finally 100 mg if needed. 3
• Atomoxetine requires 4-6 weeks at therapeutic doses to achieve full effect, so inadequate dosing and insufficient time are likely contributing to the current treatment failure. 2, 5
• The combination of a stimulant with atomoxetine is evidence-based for augmentation when monotherapy is insufficient. 3, 5

Critical Monitoring Parameters

During Dose Optimization (Weekly Visits)

• ADHD symptom severity using standardized rating scales from both patient self-report and collateral sources (work supervisor, spouse). 1, 2
• Duration of symptom control throughout the day, specifically asking about morning, midday, afternoon, and evening coverage. 1
• Cardiovascular parameters: blood pressure and pulse at each visit, as both stimulants and atomoxetine can increase these. 3, 1, 6
• Adverse effects: appetite suppression, insomnia, headaches, gastrointestinal symptoms, and mood changes. 3, 1, 2

Addressing Inadequate Duration of Effect

If Optimization Fails to Provide Full-Day Coverage

Switch to a longer-acting stimulant formulation rather than adding more medications. 1

• Lisdexamfetamine (Vyvanse) 50-70 mg once daily provides 12-14 hours of coverage and has lower abuse potential due to its prodrug formulation. 3, 1, 7
• OROS methylphenidate (Concerta) provides 10-12 hours of coverage and may be superior to immediate-release or shorter-acting formulations. 1, 5

Alternative: Add Afternoon Booster Dose

If the patient responds well to Adderall but coverage wanes in the afternoon/evening:

• Add immediate-release amphetamine 5-10 mg in the early afternoon (around 2-3 PM) to extend coverage into the evening. 1
• This strategy addresses the common issue of symptom attenuation later in the day without requiring a complete medication change. 2

Common Pitfalls to Avoid

Do not switch medications prematurely before completing a full dose range trial of the current regimen—this is the most frequent error in ADHD management. 1

Do not assume weight-based dosing is necessary—there is no evidence supporting this approach, and dosing should be based on clinical response. 1

Do not discontinue the stimulant for "drug holidays" during important work periods, as symptoms return rapidly and this disrupts functional improvement. 2

Do not combine bupropion with stimulants until further safety data are available, despite its off-label use for ADHD. 2

When to Consider Alternative Approaches

If Cardiovascular Concerns Arise

• Hold stimulants immediately if the patient develops chest pain, palpitations with concerning features (syncope, dyspnea, exercise-induced symptoms), or significant blood pressure elevation. 6
• Obtain ECG and cardiology consultation before resuming treatment. 6
• Consider switching to guanfacine extended-release or continuing atomoxetine monotherapy at optimized doses. 3

If Substance Abuse Risk is Present

• Lisdexamfetamine or atomoxetine are preferred due to lower abuse potential. 3, 5, 7
• Atomoxetine is specifically useful in patients with comorbid substance use disorders as it is an uncontrolled substance. 3, 5

Expected Timeline for Response

• Stimulant dose adjustments: Effects are immediate, so response should be evident within days of each dose increase. 1
• Atomoxetine optimization: Requires 4-6 weeks at therapeutic doses (80-100 mg) to achieve full benefit. 2, 5
• Schedule follow-up visits weekly during titration, then monthly once stable. 1, 2

Bottom Line

Your patient is significantly underdosed on both medications. Increase Adderall to 40-50 mg daily and Strattera to 80-100 mg daily over the next 4-6 weeks with weekly monitoring. 1, 2, 4 If full-day coverage remains inadequate after optimization, switch to lisdexamfetamine 50-70 mg daily or add an afternoon booster dose of immediate-release amphetamine. 1, 7 The combination of optimized stimulant and non-stimulant therapy is evidence-based and addresses both immediate symptom control and sustained all-day coverage. 3, 5