What can be added to Adderall (amphetamine and dextroamphetamine) extended release if a patient is not responding to it?

Managing Non-Response to Adderall Extended Release

For patients not responding adequately to Adderall extended release, adding extended-release guanfacine or extended-release clonidine as adjunctive therapy is recommended as these are the only medications with FDA approval for combination therapy with stimulants. 1

Assessment of Non-Response

Before adding medication, evaluate:

• Adherence to current medication regimen
• Appropriate dosing (may need optimization)
• Timing of medication administration (morning dosing with/without food)
• Duration of current trial (adequate trial period of 4-6 weeks)
• Presence of comorbidities that may affect response

Medication Options for Augmentation

First-Line Adjunctive Options:

1. Extended-release guanfacine (Intuniv)

   • Mechanism: Selective α-2A adrenergic receptor agonist
   • Starting dose: 1 mg daily
   • Titration: Increase by 1 mg weekly as needed
   • Maximum dose: 4 mg daily
   • Monitor for: Somnolence, dry mouth, dizziness, irritability, headache, bradycardia, hypotension

2. Extended-release clonidine (Kapvay)

   • Mechanism: α-2 adrenergic receptor agonist
   • Starting dose: 0.1 mg daily
   • Titration: Increase by 0.1 mg weekly as needed
   • Maximum dose: 0.4 mg daily
   • Monitor for: Somnolence, dry mouth, dizziness, bradycardia, hypotension

Important: Both medications must be tapered when discontinuing to avoid rebound hypertension 1

Alternative Approaches (Off-Label):

If first-line adjunctive options are ineffective or not tolerated:

1. Switch to a different stimulant

   • Consider methylphenidate-based products as response to amphetamine vs. methylphenidate is idiosyncratic (approximately 40% respond to both, 40% respond to only one) 1

2. Atomoxetine (Strattera)

   • Non-stimulant SNRI with some limited evidence for combination use with stimulants 1
   • Starting dose: 0.5 mg/kg/day
   • Target dose: 1.2-1.4 mg/kg/day
   • Less robust effect size (0.7) compared to stimulants (1.0)

Clinical Considerations

• Timing of doses: For patients with coverage gaps, consider adding a short-acting stimulant in the afternoon or switching to a longer-acting formulation 1

• Food effects: Unlike some extended-release stimulants, Adderall XR's absorption can be affected by food, potentially altering early drug exposure and efficacy 2

• Comorbid anxiety: If anxiety is a significant comorbid condition, adding a non-stimulant like extended-release guanfacine may be particularly beneficial 3

• Monitoring: Regular assessment of vital signs (heart rate, blood pressure), weight, sleep patterns, and mood is essential when combining medications 1

• Adolescent considerations: For adolescents, particularly those with risk of stimulant misuse or diversion, non-stimulant adjunctive medications may be preferable 1

Common Pitfalls to Avoid

1. Overlooking adherence issues: Ensure the patient is taking medication as prescribed before adding another agent

2. Inadequate dose optimization: Many apparent non-responders may benefit from dose adjustment of Adderall XR before adding another medication

3. Ignoring comorbidities: Untreated comorbid conditions (anxiety, depression, learning disorders) may contribute to apparent stimulant non-response

4. Abrupt discontinuation: Alpha-2 agonists (guanfacine, clonidine) must be tapered to avoid rebound hypertension 1

5. Excessive polypharmacy: Start with one adjunctive medication and evaluate response before considering additional agents

The combination of behavioral therapy with medication management can provide additional benefits beyond medication alone, particularly for addressing functional impairments not fully responsive to medication 1.