Can I add Adderall (mixed amphetamine salts) to Strattera (atomoxetine)?

Can You Add Adderall to Strattera?

Yes, you can add Adderall (mixed amphetamine salts) to Strattera (atomoxetine) for ADHD treatment, particularly when atomoxetine alone provides inadequate symptom control. This combination is used off-label in clinical practice and is generally safe, though evidence is limited. 1, 2

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Clinical Rationale for Combination Therapy

The primary reason for combining these medications is inadequate response to monotherapy. 2 When atomoxetine fails to provide sufficient ADHD symptom control after an adequate trial (6-12 weeks at target dose), adding a stimulant like Adderall can enhance therapeutic effect. 1, 3

Key Evidence Supporting Combination:

• Atomoxetine has smaller effect sizes (approximately 0.7) compared to stimulants (effect size 1.0), making it less effective as monotherapy for many patients 1, 4, 5
• Stimulants achieve 70-80% response rates when properly titrated, significantly higher than atomoxetine alone 1, 6
• Combination therapy may benefit patients who have tried several ADHD medications without success, though it does not work for everyone 2

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Treatment Algorithm for Adding Adderall to Strattera

Step 1: Ensure Adequate Atomoxetine Trial First

Before adding Adderall, confirm that atomoxetine has been optimized:

• Target dose: 60-100 mg daily (maximum 1.4 mg/kg/day or 100 mg/day, whichever is lower) 7, 1, 3
• Duration: Allow 6-12 weeks for full therapeutic effect 1, 3, 8
• Timing: Can be dosed once daily (morning or evening) or split into two divided doses 3, 4, 8

Step 2: Initiate Adderall at Low Dose

When adding Adderall to existing atomoxetine:

• Starting dose: 5-10 mg once daily in the morning 1
• Titration: Increase by 5-10 mg weekly based on response 1
• Target range: 10-50 mg total daily dose for adults 1
• Maximum: Up to 40 mg daily is typical, though some patients may require higher doses with clear documentation 1

Step 3: Monitor Response and Tolerability

• ADHD symptom improvement should be evident within days of starting Adderall, unlike atomoxetine's delayed onset 1
• Obtain weekly symptom ratings during dose adjustment 1
• Assess functional improvement across multiple settings (work, home, social) 1

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Safety Considerations and Monitoring

Cardiovascular Monitoring (Critical)

Both medications affect cardiovascular parameters, requiring vigilant monitoring:

• Baseline: Measure blood pressure and pulse before starting combination 1, 3
• During titration: Check BP and pulse at each dose adjustment 1, 6
• Maintenance: Monitor quarterly in adults 1
• Atomoxetine causes modest cardiovascular effects; stimulants cause greater increases (1-4 mmHg BP, 1-2 bpm heart rate) 1, 4

Contraindications to Combination Therapy

Absolute contraindications:

• Concurrent MAOI use (requires 14-day washout) 1
• Uncontrolled hypertension 1, 6
• Symptomatic cardiovascular disease 1, 6
• Active psychosis 1
• History of hypersensitivity to either medication 1

Relative contraindications (use with extreme caution):

• Active substance use disorder 1, 6
• Unstable mood disorder 1
• Marked anxiety (though recent data suggest stimulants may not worsen anxiety) 1

Common Adverse Effects

Atomoxetine-specific: Nausea, decreased appetite, somnolence, abdominal pain, fatigue 3, 4, 8

Adderall-specific: Insomnia, appetite suppression, weight loss, anxiety, headache 1

Combination may increase: Cardiovascular effects, appetite suppression, sleep disturbances 1, 4

Black Box Warning for Atomoxetine

Monitor closely for suicidal ideation, especially in children and adolescents during the first few months or with dose changes. 3, 4 This risk is heightened when combining medications, though adult trials have not shown increased incidence. 3

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Evidence Quality and Limitations

Published Evidence is Limited

The evidence base for stimulant-atomoxetine combination therapy is weak:

• Only one prospective randomized controlled trial exists 2
• Most data comes from retrospective studies and case series 2
• Small sample sizes and heterogeneous study designs limit generalizability 2
• Geographic bias in published literature 2

What the Evidence Shows

In studies of patients with ADHD receiving combination therapy:

• ADHD symptom control improved in some, but not all, patients 2
• No serious adverse events were reported 2
• Most patients were children/adolescents and male with combined ADHD subtype 2
• Methylphenidate was most commonly combined with atomoxetine (not Adderall specifically) 2

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When Combination Therapy Makes Sense

Ideal Candidates for Adding Adderall to Strattera:

1. Partial response to atomoxetine after adequate trial (6-12 weeks at target dose) 1, 3
2. Patients who benefit from atomoxetine's 24-hour coverage but need additional daytime symptom control 1, 4
3. Patients with comorbid anxiety who tolerate atomoxetine but need enhanced ADHD control (atomoxetine may help anxiety while stimulant addresses ADHD) 1, 3
4. Patients at substance abuse risk already stabilized on atomoxetine who need augmentation (atomoxetine has no abuse potential) 4, 8, 9

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Alternative Strategies to Consider First

Before resorting to combination therapy, consider:

1. Switch to stimulant monotherapy:

• Stimulants are first-line treatment with 70-80% response rates 1, 6
• Methylphenidate or amphetamines as monotherapy are more effective than atomoxetine 1, 4, 5
• Response is idiosyncratic: 40% respond to both classes, 40% to only one 6

2. Optimize atomoxetine dosing:

• Ensure dose is at 1.2-1.4 mg/kg/day or 100 mg/day maximum 3
• Allow full 6-12 weeks for therapeutic effect 3, 8
• Consider split dosing (morning and evening) to reduce side effects 3, 4

3. Add adjunctive alpha-2 agonist instead:

• Guanfacine extended-release (1-4 mg daily) or clonidine can augment atomoxetine 1, 6
• Particularly useful for hyperactivity, aggression, or sleep disturbances 1, 3
• Effect sizes around 0.7, similar to atomoxetine 1, 6

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Common Pitfalls to Avoid

1. Do not add Adderall before allowing adequate atomoxetine trial (6-12 weeks at target dose) 3, 8
2. Do not assume combination therapy will work for all patients—evidence shows benefit in some, but not all 2
3. Do not neglect cardiovascular monitoring—combination increases risk of BP/HR elevation 1, 4
4. Do not use combination therapy as first-line—stimulant monotherapy is more effective and evidence-based 1, 6
5. Do not forget that atomoxetine requires CYP2D6 metabolism—SSRIs and other CYP2D6 inhibitors can increase atomoxetine levels 3, 4

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Practical Implementation

If proceeding with combination therapy:

• Continue atomoxetine at current optimized dose (60-100 mg daily) 1, 3
• Start Adderall 5-10 mg once daily in morning 1
• Titrate Adderall by 5-10 mg weekly until symptoms improve or side effects emerge 1
• Monitor BP and pulse at each visit 1, 6
• Reassess after 4-6 weeks to determine if combination provides meaningful benefit over atomoxetine alone 1
• If no additional benefit, consider discontinuing atomoxetine and using stimulant monotherapy 1, 6