Battle of the Oral Migraine Drugs —Which One Is Best For You?

Migraine research has made huge strides in the last few years, but with so many treatment options available, it can be difficult to know where to start. Let us help you find the best oral migraine medication for you.

Danish Deep Cut

In a massive meta-analysis of over 100 research studies, Danish docs put together a list of the best, most effective migraine pills. This 2024 study compared all licenced oral drugs for adults with migraines and identified which worked the best in terms of overall pain relief, safety, and tolerability.¹

Researchers included the more recently approved oral migraine drugs (lasmiditan, rimegepant, ubrogepant) along with more widely used medications.¹ They found that these newer drugs work about as well as paracetamol and most non-steroidal anti-inflammatory drugs (NSAIDs).¹ Triptans, on the other hand seemed to be more useful but widely under prescribed.¹

If you and your doctor are developing a personal pain plan, you are in the right place. We’ve analyzed the analysis to help you figure out which combination of efficacy, speed of action and side effects is best for you.

So, get ready for our remedy ranking!

Best for immediate pain relief

When ranked for fast-acting pain relief (2 hours after the dose), the top five migraine pills were:

1. Eletriptan
2. Rizatriptan
3. Sumatriptan
4. Zolmitriptan
5. Frovatriptan

Triptans for the win here!

Best for sustained pain relief

When ranked for fast-acting pain relief (2 hours after the dose), the top five migraine pills were:

1. Ibuprofen
2. Eletriptan
3. Rizatriptan
4. Sumatriptan
5. Zolmitriptan

Triptans for the win again! Mostly. 

Best oral migraine meds for overall safety and tolerability 

When ranked for overall safety and tolerability (dizziness, nausea, sedation, fatigue), the top five migraine pills were:

1. Paracetamol
2. Naratriptan/Frovatriptan
3. Almotriptan
4. Ibuprofen
5. Celecoxib

This is more of a mix. Different types of drugs may be better at combating different symptoms, so let’s break it down for each type of side effect.

The drugs least associated with dizziness:

1. Naratriptan
2. Frovatriptan/Paracetamol
3. Almotriptan/Celecoxib
4. Ibuprofen/Naproxen sodium
5. Rimegepant

The drugs least associated with nausea:

1. Paracetamol
2. Ibuprofen
3. Frovatriptan
4. Naratriptan
5. Celecoxib

The drugs least associated with sedation (sleepiness):

1. Frovatriptan
2. Naratriptan
3. Paracetamol
4. Almotriptan
5. Ibuprofen

The drugs least associated with fatigue:

1. Almotriptan
2. Paracetamol
3. Naratriptan
4. Frovatriptan
5. Phenazone

While certain triptans do make an appearance on each of these lists, not all triptans are created equal. 

According to the researchers, dizziness was more commonly associated with triptans like  eletriptan, sumatriptan, and zolmitriptan; fatigue and sedation were more commonly associated with eletriptan; and nausea was most commonly associated with sumatriptan and zolmitriptan.¹

How were the oral migraine drugs assessed and ranked

We know MNB readers don’t just take our word for things so let me walk you through how we used the data from the researchers to create these rankings.

Seventeen migraine drugs were compared on efficacy and tolerability 

Efficacy was assessed by pain relief:

• The proportion of patients who were pain-free at 2 hours after the dose
• The proportion of patients who were pain free from 2-24 hours after the dose

Key safety and tolerability characteristics were:

• Dizziness
• Nausea
• Sedation
• Fatigue

The researchers compared the efficacy and safety of these drugs relative to each other (a head-to-head analysis) and provided the data in Figures 4 and 5 of the paper.¹ Based on those individual numbers I created 6 ranked lists: two for each of the efficacy criteria, and four for the safety criteria. 

Drugs that were ranked higher were the ones that were better at providing pain relief and least associated with side effects. 

For the overall safety ranking, I averaged the rankings for each drug to see which ones were better across all four safety and tolerability categories. 

Now, this meta-analysis only included oral drugs. Not only are there other methods of treatment for migraines (such as botox injections), but new therapies are regularly appearing on the scene (see our stories on atogepant and sex hormones).

Hopefully, this breakdown helps you get started on a conversation about the treatment options available to you!

References

1. Karlsson WK, Ostinelli EG, Zhuang ZA, et al. Comparative effects of drug interventions for the acute management of migraine episodes in adults: systematic review and network meta-analysis. BMJ. Published online September 18, 2024:e080107. doi:10.1136/bmj-2024-080107