Migraine Prevention Compared: What Recent Research Shows

For many people living with migraine, preventive treatment is essential for reducing attack frequency and improving daily function. Yet despite the availability of multiple preventive options, many patients either never start preventive therapy or discontinue it within months due to side effects or lack of improvement.

A new clinical trial called TEMPLE offers valuable insights into migraine prevention by directly comparing two commonly used treatments: atogepant (a CGRP-targeting preventive medication) and topiramate, a long-established oral preventive drug.

In this Migraine World Summit session, neurologist and headache specialist Dr. Jaclyn Duvall explains what this head-to-head research reveals about effectiveness, tolerability, and real-world treatment decisions.

Why Head-to-Head Studies Matter

Most migraine medications are initially tested against a placebo to determine whether they work better than no treatment. While these studies are essential for drug approval, they do not always answer the question patients and clinicians care about most: Which treatment works better compared to another real option?

The TEMPLE trial was designed to address that gap by comparing two preventive medications directly rather than testing them against placebo.

Because both atogepant and topiramate already have strong evidence showing they are effective migraine preventives, researchers wanted to evaluate how they perform in direct comparison—particularly in areas that matter most to patients, such as tolerability and long-term adherence.

A Major Problem in Migraine Care: Preventive Treatments Are Underused

One of the most striking realities in migraine care is that many people who qualify for preventive treatment never receive it.

Large epidemiological studies suggest that only about 10–20% of people eligible for preventive migraine therapy actually use it. Even among those who begin preventive treatment, the majority discontinue it within months.

Research shows that about 75% of patients stop preventive medications within six months.

Two key factors drive this high discontinuation rate:

• Side effects that patients find intolerable

• Delayed benefits that can take months to appear

If patients begin experiencing unpleasant side effects before seeing meaningful improvement, many decide the treatment simply isn’t worth continuing.

The TEMPLE study sought to better understand these real-world challenges.

Who Participated in the TEMPLE Trial?

The trial enrolled a broad group of migraine patients to reflect real clinical practice.

Participants included:

• Adults aged 18 to 80

• Patients with episodic or chronic migraine

• Individuals experiencing at least four migraine days per month

• Patients who had never previously used either medication

On average, participants experienced about 11 migraine days per month, indicating a moderate to high disease burden.

The study lasted 24 weeks (six months), which allowed researchers to evaluate both early responses and longer-term treatment outcomes.

Why Tolerability Was the Primary Focus

While effectiveness is important, the researchers chose tolerability as the primary focus of the study.

This decision reflects a critical reality: a medication only works if people continue taking it.

Topiramate has been used for years as a migraine preventive and has proven effectiveness. However, it is also associated with relatively high rates of side effects.

Studies estimate that 20–40% of patients stop taking topiramate due to tolerability issues.

Therefore, the TEMPLE trial focused heavily on whether patients could remain on treatment long enough to benefit from it.

Key Finding: Atogepant Was Better Tolerated

The study showed a clear difference between the two medications in terms of tolerability.

Patients taking topiramate were about two-and-a-half times more likely to discontinue treatment because of side effects compared with those taking atogepant.

This difference highlights an important factor in migraine treatment decisions: even an effective medication may fail if the side effects are difficult to tolerate.

For patients, tolerability often determines whether a preventive therapy becomes part of their long-term management plan.

Understanding the “50% Responder Rate”

Clinical trials often report a measurement called the 50% responder rate.

This term means that a patient experienced at least a 50% reduction in monthly migraine days compared with their baseline.

For example, if someone started with 10 migraine days per month, a 50% response would reduce that number to five or fewer.

However, in real life the benefits can extend beyond simple numbers. Patients may also experience:

• Shorter migraine attacks

• Less severe pain

• Improved ability to function at work or home

• Reduced disability overall

These improvements can significantly enhance quality of life even if migraine attacks do not disappear entirely.

Faster Results With Atogepant

One of the most interesting findings from the TEMPLE trial was how quickly improvements appeared.

Topiramate showed gradual improvement over time. By the end of the 24-week study period, participants experienced an average reduction of about 4.7 migraine days per month.

Atogepant, however, produced earlier improvements.

Within the first four weeks of treatment, patients experienced an average reduction of about 3.7 migraine days per month, approaching the full benefit seen with topiramate after several months.

By the end of the trial, the average reduction reached about six fewer migraine days per month with atogepant.

This faster onset of benefit can make a significant difference in patient adherence, since people are more likely to continue treatment if they see improvements quickly.

How Preventive Treatments Work Over Time

Both medications showed a common pattern seen in many migraine preventive treatments: benefits increase gradually over time.

As attacks become less frequent, the brain’s pain pathways may become less sensitized.

Migraine specialists sometimes describe this phenomenon as “pain breeding pain.” Frequent attacks can keep the nervous system in a state of heightened sensitivity. Preventive medications help interrupt this cycle by reducing attack frequency and calming the trigeminal pain pathways.

Over time, spacing attacks further apart may allow the nervous system to become less reactive.

Common Side Effects of Preventive Treatments

Each medication in the study produced side effects consistent with what clinicians already expect from these drugs.

Topiramate side effects may include:

• Tingling sensations (paresthesia)

• Fatigue

• Cognitive slowing or difficulty concentrating

Atogepant side effects may include:

• Nausea

• Constipation

Both medications were also associated with some degree of weight loss.

However, the key difference was not necessarily the type of side effects, but how many patients found them intolerable enough to stop treatment.

Why Side Effects Matter as Much as Effectiveness

Migraine is a chronic condition, and preventive treatments are often taken for extended periods—sometimes a year or longer.

Because of this, tolerability becomes just as important as effectiveness.

A medication that reduces migraine days but causes disruptive side effects may ultimately fail because patients cannot continue using it long term.

For clinicians, choosing the right preventive therapy requires balancing:

• Effectiveness

• Side effect profile

• Patient lifestyle

• Medical history

• Individual treatment preferences

  
  

Treatment Must Be Personalized

One of the most important lessons from the TEMPLE study is that clinical trial results represent group averages, not individual outcomes.

What works well for one patient may not work for another.

Treatment decisions should consider the entire person, including:

• Other medical conditions

• Job requirements

• Lifestyle factors

• Sensitivity to medication side effects

For example, a surgeon or mechanic who relies heavily on fine motor skills may find tingling sensations intolerable, while someone in another profession might be able to tolerate them more easily.

Personalization remains essential in migraine care.

When Patients Should Revisit Their Treatment Plan

Even patients who feel their migraines are “manageable” may benefit from revisiting their treatment plan periodically.

Migraine care continues to evolve rapidly, with new medications and therapies emerging in recent years.

Patients may consider reassessing their treatment if they notice:

• Increasing migraine frequency

• Greater reliance on rescue medications

• Changes in symptoms or aura patterns

• New medical conditions

• Many years since their last evaluation

Some individuals who struggled with migraine treatments a decade ago may be surprised to discover how many new options are now available.

The Future of Migraine Prevention

Research like the TEMPLE trial represents an important step forward in migraine care.

Head-to-head studies provide clinicians and patients with clearer guidance about how different treatments compare in real-world settings.

Perhaps most encouraging is the broader shift in migraine medicine toward a more ambitious goal: not just reducing migraine attacks, but striving for true migraine freedom whenever possible.

While that goal may not be achievable for every patient, continued advances in migraine prevention are helping more people move closer to it than ever before.