Can guanfacine and Adderall (amphetamine and dextroamphetamine) be used together?

Guanfacine and Adderall Combination Therapy for ADHD

Yes, guanfacine and Adderall (amphetamine and dextroamphetamine) can be used together as a combination therapy for ADHD, with guanfacine serving as an adjunctive treatment to the stimulant medication. 1

Evidence for Combination Therapy

• Guanfacine (extended-release) is one of only two medications with sufficient evidence to support its use as adjunctive therapy with stimulant medications, which has led to FDA approval for this combination 1
• The combination of alpha-2 adrenergic agonists (like guanfacine) with stimulants can be particularly beneficial when stimulant monotherapy does not provide adequate symptom control 1
• Guanfacine works through a different mechanism than Adderall - as an alpha-2A adrenergic receptor agonist that enhances noradrenergic neurotransmission in the prefrontal cortex, complementing the dopaminergic effects of stimulants 1, 2

Clinical Benefits of Combination Therapy

• The combination may provide more comprehensive symptom control by addressing different aspects of ADHD pathophysiology 1
• Guanfacine has an effect size of approximately 0.7 for ADHD symptom improvement, which can complement Adderall's effect size of approximately 1.0 1
• The addition of guanfacine may help manage certain side effects of stimulants or address symptoms that don't respond well to stimulant monotherapy 1

Dosing Considerations

• Guanfacine extended-release (Intuniv XR) is typically started at 1 mg once daily and titrated by 1 mg weekly based on response and tolerability 1
• The recommended target dose range for guanfacine is 0.05 to 0.12 mg/kg/day or 1 to 7 mg/day 1
• Adderall (mixed amphetamine salts) is typically started at 10 mg in the morning and can be titrated up to 50 mg as needed 1

Monitoring and Safety Considerations

• Monitor for potential additive side effects, particularly:

  • Cardiovascular effects: Both medications can affect blood pressure and heart rate - guanfacine may cause hypotension and bradycardia, while Adderall may increase blood pressure and heart rate 1, 3
  • Somnolence/sedation: Guanfacine commonly causes sedation, which may partially counteract the stimulating effects of Adderall 3
  • Dry mouth: Both medications can cause this side effect 3

• Regular monitoring should include:

  • Blood pressure and heart rate measurements 3
  • Assessment for sedation, dizziness, and other neurological effects 3
  • Evaluation of sleep quality and appetite 1

Potential Adverse Effects

• Common adverse effects of guanfacine include somnolence, fatigue, dry mouth, dizziness, irritability, and hypotension 3
• Common adverse effects of Adderall include appetite loss, abdominal pain, headaches, and sleep disturbance 1
• The combination therapy has not been shown to significantly increase adverse effects compared to monotherapy with either medication 4
• Contrary to some speculation, adding a stimulant does not significantly reduce the metabolic effects of other psychotropic medications 4

Important Precautions

• Do not abruptly discontinue guanfacine after prolonged use, as rebound hypertension can occur; the medication should be tapered off 3
• When initiating combination therapy, consider starting with one medication (typically the stimulant) and adding the second agent after establishing tolerability and partial response 1
• Guanfacine has interactions with CYP3A4 inhibitors and inducers, which should be considered when prescribing 1

In conclusion, the combination of guanfacine and Adderall is supported by clinical evidence and guidelines for ADHD treatment when stimulant monotherapy provides insufficient symptom control. This combination leverages complementary mechanisms of action but requires careful monitoring for potential additive side effects.