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Vyvanse

9 Vyvanse Interactions: Zoloft, Caffeine, Sudafed, and More

Alex Evans, PharmD, MBAChristina Aungst, PharmD
Written by Alex Evans, PharmD, MBA | Reviewed by Christina Aungst, PharmD
Updated on March 6, 2026

Key takeaways:

  • Vyvanse (lisdexamfetamine) is a prescription-only stimulant medication. It’s approved to treat attention-deficit hyperactivity disorder (ADHD) and binge eating disorder.

  • Many Vyvanse interactions involve medications that affect serotonin levels, such as antidepressants, triptan migraine medications, and opioids. Others are due to excess effects on the heart, such as Sudafed (pseudoephedrine), phentermine (Adipex-P, Lomaira), and other stimulants.

  • Certain Vyvanse interactions can be managed with lower dosages and close monitoring. Others may need to be avoided completely. Your prescriber can best determine how to manage these potential Vyvanse interactions.

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For many people with attention-deficit hyperactivity disorder (ADHD), Vyvanse (lisdexamfetamine) is a helpful tool for staying focused and on task during the day. But when Vyvanse is taken with certain medications, interactions — ranging from mild to severe — can happen. Knowing about interactions in advance can help you avoid unwanted side effects or other issues.

Vyvanse interactions at a glance

Below is a list of potential Vyvanse interactions. But keep in mind that other interactions are possible. Before you start taking Vyvanse, provide your prescriber and pharmacist with a current list of your medications. They can work to prevent or minimize potential Vyvanse interactions before they occur.

Medications and substances to avoid or limit while taking Vyvanse include:

  • Monoamine oxidase inhibitors (MAOIs)

  • Other stimulant medications and supplements

  • Caffeine

  • Alcohol

  • Urine alkalinizers, such as Cytra-K (potassium citrate / citric acid)

Medications that require closer monitoring when combined with Vyvanse include:

  • Selective serotonin reuptake inhibitors (SSRIs)

  • Serotonin and norepinephrine reuptake inhibitors (SNRIs)

  • Tricyclic antidepressants (TCAs)

  • Wellbutrin (bupropion)

  • Contrave (naltrexone / bupropion)

  • Triptan migraine medications

  • Opioid pain medications

  • Blood pressure medications

  • St. John’s wort

  • Lamisil (terbinafine)

  • Quinidine

  • Urine acidifiers, such as K-Phos (potassium phosphate)

Let’s take a closer look at nine of these Vyvanse interactions below.

1. MAOIs

MAOIs are an older class of antidepressants. They’re used to treat depression or symptoms of Parkinson’s disease. Examples include:

  • Emsam (selegiline)

  • Azilect (rasagiline)

  • Nardil (phenelzine)

You shouldn’t take Vyvanse with any MAOI, or for at least 14 days after stopping treatment with an MAOI. This combination can result in dangerously high blood pressure.

Vyvanse and MAOIs both increase levels of a hormone called serotonin. And combining them can put you at risk for serotonin syndrome. This is a potentially life-threatening condition caused by too much serotonin in the body. Symptoms of serotonin syndrome range from mild to severe. Examples include tremors (shakiness), a fast heart rate, and sweating. Fever and confusion are also possible.

Serotonin syndrome is more likely if you’re taking multiple medications that increase serotonin levels. As you’ll see, serotonin syndrome is a common concern with Vyvanse interactions.

2. SSRIs, such as Zoloft

SSRIs are commonly used to treat mental health conditions, such as depression and anxiety. They work by making more serotonin available in your brain. Examples include:

While rare, taking Vyvanse with an SSRI may lead to serotonin syndrome. If you need to take Vyvanse and an SSRI together, your prescriber may start you with a lower Vyvanse dosage. Tell them right away if you think you’re experiencing symptoms of serotonin syndrome. If your symptoms are severe or seem to be worsening, seek emergency medical care.

3. SNRIs, such as Effexor

There are some similarities between SNRIs and SSRIs. They’re often taken for mental health conditions, and some can also treat chronic pain. Examples of SNRIs include:

  • Effexor (venlafaxine)

  • Cymbalta (duloxetine)

  • Pristiq (desvenlafaxine)

Just like SSRIs, SNRIs make more serotonin available in the brain. But, like Vyvanse, they also increase norepinephrine levels.

Combining Vyvanse and an SNRI can put you at increased risk of serotonin syndrome. As a precaution, your prescriber may start you with a lower Vyvanse dosage. But tell them right away if you develop symptoms of serotonin syndrome.

Since Vyvanse and SNRIs increase norepinephrine, they can both also raise your heart rate and blood pressure. Taking them together can worsen this effect. Based on your health history, your prescriber can decide if this combination is OK for you to take. They may recommend taking an SSRI instead of an SNRI, for example, since SSRIs don’t affect your heart rate or blood pressure.

Good to know: St. John’s wort is an over-the-counter (OTC) supplement often used for depression. It can raise serotonin levels, similar to an SSRI or SNRI. So there’s a risk for serotonin syndrome if you take it with Vyvanse. Talk to your prescriber before adding St. John’s wort or other mood-boosting supplements to your daily regimen.

4. Wellbutrin (bupropion)

Wellbutrin is another type of antidepressant. You can take it alone or in combination with other medications. For example, it’s an active ingredient in Contrave, an oral weight-loss medication.

Wellbutrin and Vyvanse can both increase your blood pressure. This effect may be more pronounced if they’re taken together. Similar to combining an SNRI and Vyvanse, your prescriber can decide if this combination is safe for you to take. They may recommend an alternative medication or choose to monitor your blood pressure closely during treatment.

5. Triptan migraine medications

Triptan medications are used to treat migraine headaches. They attach to serotonin receptors (binding sites) in your brain and other parts of your body. Examples include:

  • Imitrex (sumatriptan)

  • Zomig (zolmitriptan)

  • Maxalt (rizatriptan)

  • Relpax (eletriptan)

Combining Vyvanse and a triptan medication can increase your risk of serotonin syndrome. But you typically only take triptans as needed for acute migraines, not as a daily medication. So the risk of this side effect may be lower than with other medications. But it’s still important to watch for symptoms of serotonin syndrome and contact your prescriber as soon as possible if they occur. If needed, they can discuss alternative migraine medications with you.

6. Opioid pain medications, such as tramadol

Tramadol (ConZip) is a prescription-only opioid medication used to treat pain. It’s one of several opioid medications known to increase serotonin levels. The effects on serotonin may vary between opioids. But all of them carry a risk of causing serotonin syndrome when combined with Vyvanse or other medications that raise serotonin levels.

Your prescriber will determine if it’s OK for you to take Vyvanse with an opioid medication. If so, they may have you keep an eye out for symptoms of serotonin syndrome. They may also suggest non-opioid pain relievers and other tips for managing pain.

7. Blood pressure medications

As mentioned above, Vyvanse can increase your blood pressure, which may be more pronounced in some people. If you’re taking medications to manage your blood pressure, they may not work as well with Vyvanse.

If you have high blood pressure or any other heart-related health conditions, let your healthcare team know before starting Vyvanse. They can decide if it’s safe for you based on your personal history. If they do prescribe you Vyvanse, they may want to monitor your blood pressure during treatment, making adjustments to your medications as needed. They may also ask you to check your blood pressure at home and let them know if any readings are higher than normal.

But if you develop chest pain, trouble breathing, or notice your heart beating differently than usual while taking Vyvanse, seek emergency care right away.

8. Other stimulants, such as Sudafed and Adipex-P

As discussed, Vyvanse is a stimulant medication. Other examples of stimulants include many other ADHD medications, some weight-loss pills such as phentermine (Adipex-P, Lomaira), and decongestants such as Sudafed (pseudoephedrine).

Some over-the-counter supplements can also contain stimulants. These ingredients include ephedra, ma huang, and guarana, among others.

It’s best to avoid combining Vyvanse with other stimulant medications unless your prescriber recommends it. Taking multiple stimulants can increase your blood pressure and heart rate. You may also be more likely to experience side effects such as insomnia and anxiety. Dangerously high blood pressure and irregular heartbeats are also possible.

Good to know: The caffeine in your morning coffee or energy drink is also a stimulant. So it’s also good to limit or avoid caffeine while taking Vyvanse. Check out a few non-caffeinated tips to get your day started with natural energy. 

Alcohol

It’s usually best to avoid or minimize alcohol consumption while taking Vyvanse. Vyvanse has stimulant effects, while alcohol has depressant effects. So the two substances can counteract each other. This combination can also increase the risk of alcohol poisoning and worsen side effects, such as increased blood pressure.

Frequently asked questions

Yes, it’s generally OK to take Vyvanse and Ozempic (semaglutide) together. But you may notice that you have less of an appetite, since both medications can affect how hungry you feel. In this case, make sure you’re getting adequate nutrition by eating nutrient-dense foods.

In addition to ADHD, Vyvanse is used to treat binge eating disorder. Some experts think that medications like Ozempic may also be able to play a role in treating binge eating disorder. But more research is needed to know for sure, and the two medications haven’t been studied together for this purpose. Your prescriber can weigh the benefits and risks of this combination.

In most cases, it’s best to avoid combining Vyvanse with another stimulant ADHD medication, such as Adderall (mixed amphetamine salts). These medications work very similarly to each other. So there may be a higher risk of side effects (without additional benefits) if you take them at the same time.

However, it’s possible that your prescriber may recommend that you take Vyvanse in the morning, then immediate-release (IR) Adderall later in the day as Vyvanse wears off. But you shouldn’t attempt to do this without your prescriber’s guidance.

No, there’s no interaction between the antibiotic amoxicillin (Amoxil) and Vyvanse. It’s fine to take these medications together. But both medications can cause nausea as a side effect, so it's a good idea to take them with food.

Yes, according to the manufacturer, you can open Vyvanse capsules and mix the contents with orange juice if you can’t swallow the pills whole. Other suggested options for mixing include yogurt and water.

Yes, diarrhea is a possible Vyvanse side effect. It often resolves on its own as your body adjusts to the medication. But if diarrhea is severe or persists, let your prescriber know.

The bottom line

It’s best to avoid taking Vyvanse (lisdexamfetamine) with monoamine oxidase inhibitors (MAOIs) and other stimulant medications. You should also avoid or limit alcohol and caffeine while taking Vyvanse.

Vyvanse can also interact with certain antidepressants, opioid pain medications, and triptans. It can also interfere with how well blood pressure medications work. If you need to take Vyvanse with one of these medications, you may need extra monitoring for unwanted side effects.

Your prescriber will determine if you can safely take another medication with Vyvanse. Talk to them or your pharmacist if you have questions about potential Vyvanse interactions.

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Why trust our experts?

Alex Evans, PharmD, MBA, has been a pharmacist for 12 years. His first job was floating in a community chain pharmacy.
Stacia Woodcock, PharmD, is a pharmacy editor for GoodRx. She earned her Doctor of Pharmacy degree from the University of Kentucky and is licensed in New York and Massachusetts.
Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

References

Foong, A., et al. (2018). Demystifying serotonin syndrome (or serotonin toxicity). Canadian Family Physician.

National Institute on Drug Abuse. (2016). Is it safe to use prescription drugs in combination with other medications?. National Institutes of Health. 

GoodRx Health has strict sourcing policies and relies on primary sources such as medical organizations, governmental agencies, academic institutions, and peer-reviewed scientific journals. Learn more about how we ensure our content is accurate, thorough, and unbiased by reading our editorial guidelines.

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