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

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.

Many Vyvanse interactions can be managed by your healthcare team ahead of time. Even so, it’s a good idea to be aware of potential interactions. While it’s not a comprehensive list, we cover what you should know about eight Vyvanse interactions below.

1. MAOIs

Monoamine oxidase inhibitors (MAOIs) are an older class of antidepressants. They can be used to treat major depression disorder or symptoms of Parkinson’s disease. Examples include selegiline (Emsam, Zelapar), rasagiline (Azilect), and phenelzine (Nardil).

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Vyvanse should not be taken 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. 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, so we’ll cover more about this condition below.

2. SSRIs like Zoloft

Selective serotonin reuptake inhibitors (SSRIs) are a class of medications that include sertraline (Zoloft). They’re commonly used to treat mental health conditions, such as depression. They work by making more serotonin available in your brain.

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While rare, taking Vyvanse with an SSRI may lead to serotonin syndrome. 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.

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 like Effexor

There are some similarities between serotonin and norepinephrine reuptake inhibitors (SNRIs) and SSRIs. They’re often taken for mental health conditions, and some can treat pain. Examples of SNRIs include venlafaxine (Effexor) and duloxetine (Cymbalta). 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 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.

4. Wellbutrin

Bupropion (Wellbutrin) is another type of antidepressant. It may be taken alone or in combination with other medications. 

Bupropion 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. Combining Vyvanse and a triptan medication can increase your risk of serotonin syndrome. 

Triptans are only taken as needed for acute migraines, so the risk of this significant side effect may be lower than with other medications. But serotonin syndrome is still possible with this combination. So it’s 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. Pain medications like tramadol

Tramadol 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 serotonin syndrome when combined with medications, like Vyvanse, 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 discuss available 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, your healthcare professional will decide if it’s safe for you to take Vyvanse. 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 monitor your blood pressure at home and let them know if any readings are higher than normal.

8. Other stimulants, like Sudafed and phentermine

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

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.

The caffeine in your morning coffee or energy drink is also a stimulant. So it may also be best to limit or avoid caffeine while taking Vyvanse. Check out a few non-caffeinated tips to get your day started with natural energy. 

Other FAQs about Vyvanse interactions

Let’s take a look at a few other frequently asked questions about Vyvanse interactions. 

Can you take Vyvanse and Adderall together?

In most cases, it’s best to avoid combining Vyvanse with another stimulant ADHD medication, such as Adderall. 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 the Vyvanse wears off. But you shouldn’t attempt to do this without your prescriber’s guidance. 

Can you take Vyvanse and Ozempic together?

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 be able to play a role in treating binge eating disorder, too. 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.

Can you take Vyvanse with orange juice?

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.

Can you drink alcohol while taking Vyvanse?

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.

When should you contact your prescriber about Vyvanse interactions?

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.

Your prescriber will determine if you can take interacting medications with Vyvanse. Some combinations should be avoided entirely, while others may require taking lower dosages or closely monitoring for potential side effects. Contact your prescriber if you notice any unusual or concerning symptoms while taking Vyvanse.

Why trust our experts?

Written by:

Brian Leonard, PharmD, BCACP, BCGP

Brian Leonard earned his doctorate in pharmacy from the University of Florida College of Pharmacy and is board certified in Ambulatory Care and Geriatric Pharmacy.

Edited by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

Reviewed by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

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