Treximet Stops Migraines by Attacking the Problem From Two Directions at Once

If you've ever wondered why Treximet works better for some people than a regular pain reliever, the answer is in its design. Treximet combines two medications — Sumatriptan and Naproxen Sodium — that each fight migraines in a completely different way. Together, they tackle both the immediate cause of migraine pain and the inflammation that keeps it going.

This article explains what Treximet is and how it works in your body, in plain English — no medical degree required.

What Treximet Does in Your Body

To understand Treximet, you need to understand what happens during a migraine. A migraine isn't just a bad headache — it's a complex neurological event involving your brain, blood vessels, and nerves.

The Migraine Process (Simplified)

During a migraine:

1. Brain signals go haywire — Certain brain cells become overactive, triggering a cascade of chemical changes.
2. Blood vessels swell — Blood vessels around the brain dilate (expand), which contributes to the throbbing pain.
3. Nerves get inflamed — The trigeminal nerve (the main pain nerve in your head and face) releases inflammatory chemicals called neuropeptides, which make the pain worse and longer-lasting.
4. Inflammation builds — Prostaglandins and other inflammatory molecules pile on, amplifying pain and sensitivity.

How Sumatriptan Works (The Triptan Component)

Think of Sumatriptan as the emergency brake for your migraine.

Sumatriptan targets serotonin receptors — specifically the 5-HT1B and 5-HT1D receptors — on blood vessels and nerves in your brain. Here's what it does:

• Constricts swollen blood vessels — By activating 5-HT1B receptors on blood vessel walls, Sumatriptan tells the dilated vessels to narrow back down. Less swelling means less throbbing pain.
• Quiets the trigeminal nerve — By activating 5-HT1D receptors on nerve endings, Sumatriptan blocks the release of inflammatory neuropeptides. This is like turning off the alarm signal that's telling your brain "PAIN."

Analogy: Imagine your migraine is a fire. Sumatriptan is like turning off the gas line — it stops the fuel (swollen vessels and nerve signals) that's feeding the fire.

How Naproxen Sodium Works (The NSAID Component)

Naproxen Sodium handles the cleanup.

Naproxen Sodium is an NSAID that blocks enzymes called COX-1 and COX-2. These enzymes produce prostaglandins — chemicals that promote inflammation, pain, and fever. By blocking prostaglandin production, Naproxen Sodium:

• Reduces inflammation around the blood vessels and nerves
• Lowers pain sensitivity so signals reaching your brain feel less intense
• Helps prevent migraine recurrence — This is a key benefit. Inflammation can linger even after the initial migraine eases, causing the headache to come back hours later. Naproxen's longer-lasting anti-inflammatory effect helps prevent this rebound.

Analogy: If Sumatriptan turns off the gas line, Naproxen Sodium is the fire extinguisher that puts out the remaining flames and keeps them from reigniting.

Why the Combination Works Better

Clinical studies showed that the combination of Sumatriptan and Naproxen Sodium in a single tablet provided better migraine relief than either ingredient alone. Specifically:

• More patients were pain-free at 2 hours
• Fewer patients experienced migraine recurrence within 24 hours
• The combination provided sustained pain relief, meaning the migraine was less likely to come back

The dual mechanism — stopping the migraine trigger (Sumatriptan) while cleaning up the inflammation (Naproxen Sodium) — addresses the migraine from both angles simultaneously.

How Long Does Treximet Take to Work?

Most people begin to feel relief within 30 minutes to 1 hour after taking Treximet. The Sumatriptan component starts working quickly to constrict blood vessels and quiet nerve signals. The Naproxen Sodium takes a bit longer to fully kick in but provides longer-lasting pain relief.

For best results, take Treximet at the very first sign of a migraine — the earlier you take it, the better it works. Waiting until the migraine is at full intensity makes it harder for any medication to provide complete relief.

How Long Does Treximet Last?

The pain relief from Treximet typically lasts up to 24 hours, though this varies by person. The Naproxen Sodium component has a half-life of about 12–17 hours, which means it stays active in your system longer than Sumatriptan alone (which has a half-life of about 2 hours). This extended anti-inflammatory effect is a big reason why Treximet is better at preventing migraine recurrence.

If your migraine returns or doesn't fully resolve after the first dose, you can take a second tablet after at least 2 hours. The maximum dose is 2 tablets in 24 hours.

What Makes Treximet Different From Similar Medications?

Treximet vs. Sumatriptan (Imitrex) Alone

Sumatriptan by itself is highly effective for many migraine sufferers. However, some patients find that their migraines come back within 24 hours after taking Sumatriptan alone. Treximet's Naproxen component helps prevent this recurrence. If you've tried Sumatriptan and found that migraines tend to return later the same day, Treximet may be a better option.

Treximet vs. Taking Sumatriptan + Aleve Separately

Some people take Sumatriptan and over-the-counter Naproxen Sodium (Aleve) as separate tablets. This is a common and often cheaper approach. However, Treximet uses a specific formulation (called RT Technology) that's designed for faster absorption. Whether that difference matters clinically depends on the individual — discuss it with your doctor.

Treximet vs. Other Triptans

There are several other triptans available, including Rizatriptan (Maxalt) and Eletriptan (Relpax). These work through the same serotonin receptor mechanism as Sumatriptan but differ in how quickly they work, how long they last, and their side effect profiles. None of them include a built-in anti-inflammatory component like Treximet does. For a comparison, see our guide on alternatives to Treximet.

Treximet vs. CGRP Medications (Ubrelvy, Nurtec)

Newer migraine medications like Ubrogepant (Ubrelvy) and Rimegepant (Nurtec) work through a completely different mechanism — they block CGRP (calcitonin gene-related peptide), a molecule involved in migraine signaling. These medications have fewer cardiovascular concerns than triptans and may be options for patients who can't take Treximet due to heart-related contraindications.

Final Thoughts

Treximet's dual-action approach — constricting blood vessels and calming nerve signals (Sumatriptan) while reducing inflammation and preventing recurrence (Naproxen Sodium) — makes it one of the most comprehensive single-tablet migraine treatments available. It typically starts working within 30–60 minutes and provides relief that can last up to 24 hours.

If you're interested in trying Treximet, learn about potential side effects and how to find a prescriber. And when you're ready to fill your prescription, use Medfinder to find a pharmacy with Treximet in stock near you.