Can you take modafinil (provigil) and Adderall (amphetamine and dextroamphetamine) together?

Concurrent Use of Modafinil and Adderall

Taking modafinil (Provigil) and Adderall (amphetamine and dextroamphetamine) together is not recommended due to the increased risk of cardiovascular side effects, potential for additive stimulant effects, and limited evidence supporting safety of this combination.

Pharmacological Considerations

Mechanism of Action

• Modafinil: Wake-promoting agent that affects dopamine and other neurotransmitters
• Adderall: Amphetamine-based stimulant that increases norepinephrine and dopamine

Drug Interactions

• The FDA label for modafinil specifically lists interactions with CNS active drugs including dextroamphetamine 1
• While pharmacokinetic studies show no significant alterations in the pharmacokinetic profile when modafinil is combined with dextroamphetamine, this doesn't guarantee clinical safety 1, 2

Safety Concerns

Cardiovascular Risks

• Both medications independently can increase blood pressure and heart rate
• Combined use may potentially amplify these effects, increasing risk of:
  • Hypertension
  • Tachycardia
  • Arrhythmias

Neurological/Psychiatric Risks

• Additive CNS stimulation may lead to:
  • Increased anxiety
  • Insomnia
  • Potential for increased risk of seizures
  • Exacerbation of underlying psychiatric conditions

Evidence on Combined Use

A small study in healthy male volunteers found that single doses of modafinil (200 mg) and dextroamphetamine (10 mg) administered together had no clinically significant effects on the pharmacokinetic profile of either agent 2. However:

• This was only a single-dose study
• It involved healthy volunteers, not patients with ADHD or narcolepsy
• There was a slightly greater incidence of adverse events when the drugs were administered together 2

Alternative Approaches

For ADHD Treatment

• If Adderall is ineffective or causing side effects:
  • Try another stimulant class (methylphenidate) before adding modafinil 3
  • Consider non-stimulant options like atomoxetine, extended-release guanfacine, or extended-release clonidine 3

For Sleep Disorders

• A recent randomized, blinded trial comparing modafinil to amphetamine-dextroamphetamine for narcolepsy type 2 and idiopathic hypersomnia found that:
  • Both medications improved sleepiness
  • Anxiety was more common with modafinil
  • Appetite suppression was more common with amphetamine-dextroamphetamine 4
  • This suggests using one or the other, not both together

Special Populations

Patients with Substance Use Disorders

• Use extreme caution with stimulant combinations in patients with history of substance abuse
• Non-stimulant options may be preferable 3

Pregnant Patients

• Both medications should be used with caution in pregnancy
• Recent evidence suggests modafinil alone may not increase risks for neurodevelopmental disorders, impairments in vision or hearing, epilepsy, seizures, or growth impairment 5

Conclusion

While limited data exists on the specific combination of modafinil and Adderall, the potential risks of additive stimulant effects outweigh the benefits for most patients. If one medication is not providing adequate symptom control, it is generally safer to:

1. Optimize the dose of a single agent
2. Switch to an alternative medication
3. Consider non-stimulant options

Always consult with a healthcare provider before combining these medications or making changes to your treatment regimen.