Nausea One Reason Triptans Can Fail in Acute Migraine Treatment

Patient Expert
Medically Reviewed

When the most often prescribed acute treatments for migraine fail, patients and doctors alike want to know why. In fact, such issues are so important to doctors and researchers that there was an entire _ special issue_ of the journal Headache devoted to the gastrointestinal manifestations of migraine. One _ research paper_ in this issue dealt specifically with why triptan treatment can fail.

The Paper:

Paper Background:

"Results of randomized, double-blind, controlled studies establish the efficacy of triptans in the acute treatment of migraine, but triptan benefits demonstrated in clinical trials have not consistently been realized in clinical practice. This paper explores the contribution of gastrointestinal manifestations of migraine – namely nausea (with or without vomiting) and gastroparesis – to triptan treatment failure."

Triptans for Migraine:

There are seven triptans available for the acute treatment of Migraine available in a variety of formulations.

  • All of them are available in oral tablets.
  • Two are available in orally disintegrating tablets. Some patients mistakenly think they're to be placed under the tongue and are absorbed via the oral mucosa. This is not the case. They should be allowed to disintegrate on the tongue, and they are swallowed with saliva and absorbed via the gastrointestinal tract.
  • Two are available in nasal spray formulation.
  • One is available in subcutaneous injectable formulation.

The results of randomized, double-blind, controlled studies established the efficacy of the triptans, but the benefits of triptans that were shown in the clinical trials haven't occurred consistently in use. Results of later studies showed patients to be highly dissatisfied with current acute migraine treatments. One study conducted in three migraine and headache centers showed that 37% of the patients who used oral triptans were dissatisfied with the time it took to get relief from them. That dissatisfaction with treatment has been linked to patients discontinuing using triptans. Furthermore, it may be why studies have shown a low rate of patients using triptans and a high patient turnover in practices.

The reasons acute migraine treatment fail are often related to:

  • the diagnosis being incorrect or incomplete;
  • patients and doctors failing to address important exacerbating factors because they missed them;
  • dietary or lifestyle triggers;
  • combination treatment required;
  • unrealistic expectations for treatment;
  • need for inpatient treatment;
  • using acute medication too frequently;
  • poor absorption;
  • incorrect use of acute medications.

The Importance of Gastrointestinal Symptoms and Signs In Migraine:

Failing to take into account how vastly different migraineurs and each migraine attack can be may be part of the explanation for the high rates of patient dissatisfaction with triptans, their relatively low usage, and high patient turnover mentioned above. The current acute migraine treatments, dominated by oral triptans, don't address these differences. Although oral triptans are effective for many of the different migraine attacks a patient may experience, they're not the best treatment for every migraine attack or for every migraineur. Specifically, oral triptans are not best for treating migraine attacks with gastrointestinal symptoms.

More than 73% of migraineurs have experienced nausea (with or without vomiting) during their migraine attacks. Most of them experience nausea during most of their migraines. When compared to migraineurs who don't experience nausea during a migraine or rarely experience it, those with high-frequency nausea during their migraines were more likely to experience other migraine symptoms frequently, to be disabled by migraine, for their migraines to have greater impact, and more. (See Nausea of Migraine Impacts Disease Burden and Quality of Life.)

Nausea is a predictor of poor response to oral triptans. It's not yet understood why that's the case. There are several possibilities:

  • It may be that nausea is a sign of severe and debilitating migraines.
  • It may be that nausea affects the medication-taking behavior of patients. Patients might avoid or delay taking oral medications because of the nausea. This would result in a reduction of the efficacy of the medications.
  • Another possibility is that most of the medication is expelled when vomiting accompanies the nausea.

Another gastrointestinal problem that can affect the efficacy of oral medications is gastroparesis. There are studies that have shown gastroparesis to be common among migraineurs, during and between attacks. Gastroparesis is a partial paralysis of the stomach that results in delayed stomach emptying of both solids and liquids. This can impede the absorption of medications.

Implications of Gastrointestinal Symptoms in Migraine:

Migraine-related nausea and vomiting as well as migraine-associated gastroparesis are prevalent and have a high impact. To date, these issues haven't been properly addressed in the acute treatment of migraine, which still relies mostly on oral triptans. Various points above are sufficient to explain why oral treatments aren't the best treatment choice when migraine-related nausea and/or gastroparesis are a factor. Because of nausea, patients may delay or avoid taking oral medications. Additionally, when they are taken, gastroparesis may impair or prevent their working effectively.

Many patients fear or dislike needles, so injections aren't the best option for many. Nasal sprays can increase nausea for some patients, and they rely partly on gastrointestinal absorption, making nausea and gastroparesis problematic for them as well.

Summary and Comments:

Nausea, vomiting, and gastroparesis have significant impact on acute migraine treatment, impairing and impeding their effectiveness. Many of the other reasons for triptan failure can be addressed by patient education and better partnerships between doctors and patients:

  • patients and doctors failing to address important exacerbating factors because they missed them;
  • dietary or lifestyle triggers;
  • unrealistic expectations for treatment;
  • need for inpatient treatment;
  • using acute medication too frequently;
  • incorrect use of acute medications.

Nausea, vomiting, and gastroparesis, however, are issues that need to be addressed through research and better treatment options.

Nausea is actually one of the possible symptoms listed for diagnosis of migraine in the International Headache Society's International Classification of Headache Disorders (ICHD). Patients have reported severe nausea as well as vomiting for as long as I can remember. One issue I find troubling is that it has taken so long for the implications of nausea and vomiting in acute treatment to be investigated and addressed. Yes, it would be best to understand the "why" behind these symptoms, but why has it taken so long to seriously look at alternative forms of delivery for triptans? Why, 22 years after the introduction of the first triptan and 19 years after the introduction of the first oral triptan, are oral triptans the dominant acute migraine treatment? Anti-emetics (medications to reduce nausea and vomiting) have come in many delivery forms for years - tablets, injections, suppositories, transdermal patches.

A look at new treatments in development and recently approved by the FDA shows that, in addition to new medications, new delivery systems are finally being developed for triptans. At last.


Newman, Lawrence C., MD. "Why Triptan Treatment Can Fail: Focus on Gastrointestinal Manifestations of Migraine." Headache 2013;53;S1:11-16.

Live well,

PurpleRibbonTiny Teri1

Make a difference... _Donate to the 36 Million Migraine Campaign! _

Follow me on    or