Triptans and Add-On Therapy: Effects on Headache-Related Disability

The practice of combining acute treatments for migraine is common, but not well studied. Real-world data from the American Migraine Prevalence and Prevention (AMPP) Study were used to evaluate how treatment changes affect migraine outcomes.1

Study Design

The AMPP Study is a longitudinal, population-based study in the United States. Questionnaires were mailed annually between 2005 and 2009 to 24,0000 adults who had had at least one severe migraine in the year before the survey began. Participants were asked to provide information about headache symptoms and frequency, disability, productivity, medications, sociodemographics, and comorbidities.

Participants who completed the questionnaire in 2005 and two other consecutive years were included in this analysis.1 The main exposure in this analysis was the addition of an acute treatment to a triptan, and the primary outcome was change in headache-related disability, assessed using the Migraine Disability Assessment Scale (MIDAS). Participants were grouped according to whether they added a second triptan (n=111), an opioid/barbiturate (n=118), or NSAID (n=69) from one year to the next, and compared with participants whose treatment regimen did not change (consistent-treatment groups). The analysis was stratified according to headache frequency:

  • Low-frequency episodic migraine (LFEM; 0-4 migraine days/month)
  • Moderate-frequency episodic migraine (MFEM; 5-9 migraine days/month)
  • High-frequency episodic migraine and chronic migraine (HFEM/CM; 10+ migraine days/month)


In the consistent-treatment groups, the prevalence of LFEM was about 11%, MFEM was 22%, and HFEM/CM was about 66%.1 For patients who received an add-on therapy, the distribution of headache frequency varied by therapy type (Table).1 For example, 18.0% of the people who added a second triptan had LFEM, whereas only 4.4% of the people who added an NSAID had LFEM. Sixty-one percent of the people who added a second triptan had HFEM or CM, whereas 76.8% of the people who added an NSAID had frequent migraines.

Distribution of Headache Frequency by Add-On Therapy


Source: Buse DC, et al. Headache. 2015 Apr 17.

Overall, none of the adjusted or unadjusted models showed any significant difference in disability between adding a treatment or maintaining a consistent regimen.1 However, a few statistically significant differences emerged when analyzed by migraine frequency. In particular, adding a second triptan or NSAID was associated with an increase in disability for patients with HFEM/CM. Conversely, adding a triptan or NSAID was associated with decreased disability for patients with MFEM. The addition of an opioid or barbiturate was not beneficial for any group. Adjustment for sex, age, BMI, or annual household income did not significantly change the results.

The authors speculate that differences in the effect of adding a NSAID by headache frequency may be related to confounding that cannot be measured in this observational study.1 For example, there may be differences between the patients with HFEM and CM that are obscured when this group is consolidated. Patients with HFEM often progress to CM over the course of the year, so the results of this study may reflect significant disease worsening in this group of patients. Conversely, the finding that adding NSAIDs is associated with improvements in headache-related disability for patients with less frequent migraine is consistent with clinical experience and trials.


This study is based on self-reported data based on recall over the previous one to three months. Questions about medication were based on usage in the previous month, whereas disability was assessed over the previous three months. Therefore, an assumption was made that one-month medication usage reflected three-month medication usage. The questionnaires did not capture specific information about the dose and timing of medications used. Confounding is likely because medication changes are often made due to changes in clinical status, which is related to the study’s primary outcome.


The authors concluded that adding an acute medication to triptan therapy is not an effective strategy for reducing headache-related disability for most patients. An exception is patients with MFEM, who may benefit from the addition of an NSAID when triptan therapy alone is insufficient. They authors state that their results reflect the presence of a widespread, unmet need for alternative treatment strategies.

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