Triptans vs. CGRP Antagonists: 5 Differences Between These Popular Migraine Medications

Living with migraines can be tough. They’re unpredictable and disrupt your daily life. Thankfully, there are many migraine treatments that can offer relief.

If you have migraines, you’ve likely looked into some of these treatment options. Triptans and calcitonin gene-related peptide (CGRP) antagonists are two popular kinds of migraine medications. Triptans have been around since 1992, and the FDA approved the first CGRP antagonist in 2018.

So, how do triptans compare to CGRP antagonists for migraines? Below, we’ll cover five key differences to help you and your healthcare provider decide which medication might be the right fit for you.

1. Triptans and CGRP antagonists manage migraines differently

Triptans and CGRP antagonists have unique mechanisms of action. Meaning, they fight your migraines using different strategies.

During a migraine attack, blood vessels in the brain can swell up, leading to pain and other symptoms. Triptans work by binding to specific receptors (chemical binding sites) throughout your body to reduce blood vessel swelling. What’s more, triptans block pain signals coming from your nerves.

CGRP antagonists work by blocking CGRP from doing its job. CGRP is a neurotransmitter (chemical messenger) that can trigger migraines. Studies show that people who experience migraines have higher levels of CGRP in their body.

2. They both come in several dosage forms

Triptans and CGRP antagonists are available as oral tablets. But they come in many other dosage forms, too. This gives you flexibility in how to manage your migraines. Below, we’ll list the available migraine medications and their dosage forms.

List of triptans

Here are the available triptans and their dosage forms.

List of CGRP antagonists

All CGRP antagonists are currently available as brand-name-only products. Here are the available CGRP antagonists and their dosage forms.

• Nurtec ODT (rimegepant), an orally disintegrating tablet

• Ubrelvy (ubrogepant), an oral tablet

• Qulipta (atogepant), an oral tablet

• Zavzpret (zavegepant), a nasal spray

• Emgality (galcanezumab-gnlm), an under-the-skin injection

• Aimovig (erenumab-aooe), an under-the-skin injection

• Ajovy (fremanezumab-vfrm), an under-the-skin injection

• Vyepti (eptinezumab-jjmr), an intravenous (IV) infusion

3. Triptans don’t prevent migraines

Studies suggest that triptans may be more effective than CGRP antagonists for treating migraines. But triptans are only FDA approved for the treatment of migraines. They can’t prevent them. And they’re most effective when they’re taken as soon as your migraine symptoms start. They may not work as well if you wait to take a dose until your migraine symptoms are fully underway.

What’s more, due to side effect risks, you shouldn’t take triptans more than 2 days per week. Talk with your healthcare provider if you find yourself needing more migraine relief. You may need to try another medication to prevent migraines.

Many CGRP antagonists do prevent migraines

CGRP antagonists can be used for migraine treatment and/or prevention. Here’s a breakdown:

Keep in mind: Every CGRP antagonist is FDA approved to treat or prevent a specific type of migraine. Your healthcare provider can help you choose the right CGRP antagonist based on your symptoms.

4. CGRPs generally have fewer side effects, but each class has its own risks

Like all medications, triptans and CGRP antagonists can cause side effects. But studies show that CGRP antagonists generally cause fewer side effects than triptans.

Common triptan side effects include:

• Nausea

• Dizziness

• Tingling sensations on the skin

• Chest tightness

• Flushing (facial redness)

Some of the most common CGRP antagonist side effects include:

• Injection site reactions (itching, redness, pain) for injectable medications

• Nausea

• Constipation

• Fatigue

Good to know: Side effects for both triptans and CGRP antagonists vary by medication and dosage form. Discuss the risks of a specific medication with your healthcare provider or pharmacist.

Serious side effects

Triptans can constrict blood vessels throughout your entire body. This can increase your risk of serious heart-related problems, including heart attack and stroke. For this reason, people with heart problems shouldn’t take triptans.

Some CGRP antagonists are monoclonal antibodies that are injected into your body. Monoclonal antibodies are human-made proteins that mimic parts of your immune system. CGRP antagonists could trigger your immune system and cause an allergic reaction. These reactions can range from mild to life-threatening.

Although these serious side effects are rare, it’s important to be aware of them.

5. Triptans are available as lower-cost generics

All triptans and CGRP antagonists are prescription-only medications. But triptans are generally more affordable. Over time, lower-cost, generic triptans have become available.

It’s also important to note that many health insurance plans require a prior authorization (PA) for CGRP antagonists. With a PA, your healthcare provider must submit additional paperwork to your insurance provider before they’ll cover the cost of your medication. Since there are less expensive medications on the market, such as triptans, insurance companies may ask you to try those options first.

What’s more, due to side effect concerns, insurance companies often limit how many triptan doses you can receive in a month. For example, your insurance company may only cover 9 tablets per month. Your provider may need to fill out a PA form if you need more than their set monthly limit.

Insurance exceptions like this can lead to delays with picking up your prescription.

When should you consider a CGRP antagonist over a triptan (or vice versa)?

According to the American Headache Society, triptans are a first-choice option for treating moderate-to-severe migraines. CGRP antagonists are more of a second choice option. But many CGRP antagonists work especially well for migraine prevention.

In certain situations, your healthcare provider may recommend one medication type over the other.

Cardiovascular disease

You should avoid triptans if you have a history of heart-related health conditions, including:

• High blood pressure that isn’t well controlled

• Coronary artery disease

• Peripheral artery disease

• Previous heart attack

• Previous stroke

CGRP antagonists may be a better choice for people with these conditions. In fact, studies suggest that CGRP antagonists may be beneficial in some cardiovascular diseases.

Drug interactions

Several medications and supplements can interfere with how your body processes triptans or CGRP antagonists. Your healthcare provider may recommend adjusting your medication dosages or avoiding certain medications altogether.

For instance, triptans should be avoided with medications that raise serotonin levels. This interaction can cause a rare but serious condition called serotonin syndrome. Symptoms of serotonin syndrome can include sweating, confusion, and involuntary body movements. Examples of medications that affect serotonin include:

• Selective serotonin reuptake inhibitors (SSRIs) such as sertraline (Zoloft)

• Serotonin and norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta)

• St. John’s wort

CGRP antagonists have some interactions, too. For instance, Qulipta and Nurtec ODT are broken down by certain enzymes (proteins) in your liver. Ketoconazole, phenytoin (Phenytek, Dilantin), and clarithromycin (Biaxin XL) can interfere with these enzymes and cause problems.

Keep in mind: All medications have their own unique interactions. Be sure to discuss your entire medication list with your pharmacist.

Kidney or liver problems

If you have moderate-to-severe kidney or liver problems, CGRP antagonists may be a better option for migraine relief. This is because people with severe kidney or liver problems shouldn’t take triptans. They haven’t been very well studied in these populations.

Can you take triptans with CGRP antagonists?

No. It’s not recommended to combine triptans with CGRP antagonists. If you’re taking either medication and you feel like your migraines aren’t adequately controlled, reach out to your provider. They can make recommendations to shake up your medication routine.

Why trust our experts?

Written by:

Sheila McAdoo, PharmD

Sheila McAdoo, PharmD, is a licensed pharmacist in Virginia, New York, and the District of Columbia. She has worked in the pharmacy industry for 12 years and currently works as a community pharmacist.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Christina Aungst, PharmD

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.

Our editorial standards

Meet our experts