Study suggests need to reevaluate efficacy outcomes in non-drug headache research

Mindfulness-based stress reduction (MBSR) was beneficial for secondary endpoints in migraineurs, but not for the primary endpoint of migraine frequency, a randomized clinical trial found.

Migraine frequency over 12 weeks improved equally well for patients who had MBSR (−1.6 migraine days per month, 95% CI −0.7 to −2.5) and headache education (−2.0 migraine days per month, 95% CI −1.1 to −2.9), reported Rebecca Erwin Wells, MD, MPH, of Wake Forest University and co-authors.

In other outcomes, MSBR showed greater benefit than headache education. “Compared with headache education, MBSR participants had improvements in headache-related disability, quality of life, depression scores, self-efficacy, pain catastrophizing, and decreased experimentally induced pain intensity and unpleasantness out to 36 weeks,” Wells and colleagues wrote in JAMA Internal Medicine.

“Although we hypothesized that MBSR would decrease migraine frequency, we did not expect headache education would also decrease frequency, with both groups having clinically meaningful decreases,” they noted.

The trial compared migraine patients randomized to either MBSR (standardized training in mindfulness/yoga) or headache education (migraine information). Both were given for 8 weeks at 2 hours per week.

Compared with the headache education group, the MBSR group had improvements from baseline at all follow-up time points – 12, 24, and 36 weeks – shown as between-group differences on measures of:

  • Disability: −5.92, 95% CI 2.8-9.0, P<0.001 on the Migraine Disability Assessment
  • Quality of life: 5.1, 95% CI 1.2-8.9, P=0.01, on the Migraine-Specific Quality of Life Questionnaire
  • Self-efficacy: 8.2, 95% CI 0.3-16, P=0.04, on the Headache Management Self-Efficacy Scale
  • Pain catastrophizing: −5.8, 95% CI 2.9-8.8, P=0.001 on the Pain Catastrophizing Scale
  • Depression scores −1.6, 95% CI 0.4-2.7, P=0.008 on the Patient Health Questionnaire-9

Sensory testing results revealed that MBSR participants reported a greater decrease in percent change from baseline for perception of experimental pain unpleasantness and intensity, while the headache education group showed no significant change.

Improvements for anxiety and mindfulness for MBSR were not statistically significant, and the group found no significant differences in medication use (headache-specific or all medications) between groups. No significant changes over time or group differences on headache pain unpleasantness, intensity, or duration were noted.

“Wells and colleagues are among a growing group of pioneers evaluating the potential of nonpharmacological treatments for chronic pain conditions,” noted Daniel Cherkin, PhD, of Kaiser Permanente Washington Health Research Institute in Seattle, in an accompanying editorial. “These trials, which reflect a shift from predominantly pharmacological approaches, require new ways of thinking about key aspects of study design, including choices of comparison groups and primary outcome measures. Such trials have the potential to provide clinicians an opportunity to offer patients safer treatment options that more effectively reduce the amount of pain experienced and improve function.”

“While the conclusion based on the primary outcome measure, migraine frequency, is likely valid, it would not be appropriate to conclude from this trial that MBSR is ineffective for migraine given the positive results for multiple secondary outcomes,” Cherkin added. “In fact, the preponderance of evidence from this trial suggests otherwise. This raises an important question: what outcome should be considered primary in trials of nonpharmacological treatments for migraine?”

Since inclusion in the Global Burden of Disease listings in 2000, migraine as a source of disability has moved from 19th to sixth in 2013, and second in the latest report with data from 2019.

Concerns about treatment efficacy and adverse effects have led to interest in non-pharmacologic treatment options. A 2017 systematic review concluded that “self-management interventions for migraine and tension-type headache are more effective than usual care in reducing pain intensity, mood and headache-related disability, but have no effect on headache frequency. Preliminary findings also suggest that including cognitive behavioral therapy, mindfulness and educational components in interventions, and delivery in groups may increase effectiveness.”

In this trial, Wells and colleagues studied 89 adult patients who experienced between 4 and 20 migraine days per month. Most (92%) were female. Their mean age was 44 and they had an average of 7.3 migraine days monthly.

Both groups had similar current use of acute treatment (87% overall), but 40% of the MBSR group versus 71% of the education group were using a migraine prophylactic (P=0.01). Anxiety (43%) and depression (38%) also were common overall.

“Mindfulness may strengthen cognitive and affective regulation of nociceptive input by training individuals to reassess sensory percepts (including pain) in a nonjudgmental way by modifying their appraisal of, and ’turning towards’ pain, resulting in decreased nociception,” Wells and co-authors wrote.

“The changed pain perception, coupled with clinically meaningful improvements in cognitive/ affective processes, both out to 36 weeks, suggests that MBSR participants learned a new way of processing pain that may have significant effect on long-term health,” they added.

Limitations of the study include lack of an inactive control group. The cohort was also restricted to patients available for 2-hour sessions each week for 8 weeks which may have introduced bias, along with the population overall which was mostly white, highly educated, and healthy.

“Although the authors included a reasonable active control group, headache education, the absence of a usual care comparator makes it impossible to estimate the effect of incorporating MBSR as a treatment option for migraine into usual care,” Cherkin observed. “The current trial may have underestimated the effectiveness of MBSR compared with usual care alone.”

  1. Mindfulness-based stress reduction (MBSR) was beneficial for secondary endpoints in migraineurs, but not for the primary endpoint of migraine frequency, a randomized clinical trial found.

  2. Migraine patients who participated in MBSR had improvements in headache-related disability, quality of life, depression scores, self-efficacy, and pain catastrophizing out to 36 weeks.

Paul Smyth, MD, Contributing Writer, BreakingMED™

This study was funded by an American Pain Society Grant from the Sharon S. Keller Chronic Pain Research Program, and the National Center for Complementary and Integrative Health.

Wells reported grants from NIH.

Cherkin reported no conflicts of interest.

Cat ID: 35

Topic ID: 82,35,486,730,35,394,141,192,922,925