Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes

Abstract

We aimed to evaluate the efficacy of an enhanced mindfulness-based stress reduction (MBSR+) vs stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n = 50) with SMH (n = 48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then biweekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. Magnetic resonance imaging (MRI) outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula to DLPFC and cognitive task network, and gray matter volume of DLPFC, dorsal anterior insula, and anterior midcingulate. Secondary outcomes were headache-related disability, pain severity, response to treatment, migraine days, and MRI whole-brain analyses. Reduction in headache days from baseline to 20 weeks was greater for MBSR+ (7.8 [95% CI, 6.9-8.8] to 4.6 [95% CI, 3.7-5.6]) than for SMH (7.7 [95% CI 6.7-8.7] to 6.0 [95% CI, 4.9-7.0]) (P = 0.04). Fifty-two percent of the MBSR+ group showed a response to treatment (50% reduction in headache days) compared with 23% in the SMH group (P = 0.004). Reduction in headache-related disability was greater for MBSR+ (59.6 [95% CI, 57.9-61.3] to 54.6 [95% CI, 52.9-56.4]) than SMH (59.6 [95% CI, 57.7-61.5] to 57.5 [95% CI, 55.5-59.4]) (P = 0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. Enhanced mindfulness-based stress reduction is an effective treatment option for episodic migraine.

Figure 1.

Participant Flow Through Trial Comparing Extended Minfulness Based Stress Reduction and Stress Management for Migraine Headache. ^a – Of the 50 participants randomized to receive enhanced mindfulness-based stress reduction, 43 completed all 12 sessions. Participants were recruited in 8 separate cohorts (range of 4–8/cohort). ^b – Of the 48 participants randomized to receive stress management for headaches, 40 completed all 12 sessions. Participants were recruited in 8 separate cohorts (range of 2–11/cohort).

Figure 2.

Clinical outcomes. Mean (thick lines; 95% confidence intervals shown in thin lines) number of headache days per 28-day diary (uncorrected values) for SMH (gray) and MBSR+ (black). Responder rates (with response defined as a 50% reduction in headach days from baseline) are shown in bar plots, with MBSR+ in red and SMH in blue. At week 20 (primary outcome) both headache frequency and response rate were significantly better in the MBSR+ group.

Figure 3.

MRI outcomes. A) Regions-of-interest for primary outcome analyses. The activation map is defined from the baseline the baseline group map (all patients) for activation during the cognitive task (difficult vs easy contrast on the multi-source interference task). The circled regions show the five ROIs derived from this map (left and right dorsal anterior insula (aINS), left and right dorsolateral prefrontal cortex (DLPFC), and anterior midcingulate cortex (aMCC). These ROIs were used to assess the primary MRI outcomes, which included structure, resting state connectivity, and pain- and cognitive-related activation. There were no significant effects of treatment for region-of-interest analyses. B) Whole-brain (secondary outcome) analysis interaction effect for cognitive task-related activation. The SwE model assess the interaction between treatment and time for the difficult vs easy contrast on the multi-source interference task. Identified regions show a decrease in activation level in the MBSR+ compared to SMH group over time. C) Whole-brain analysis interaction effect for left dorsal aINS resting state connectivity. Regions show a decrease in activation level in the MBSR+ compared to SMH group over time. Images are displayed on the average anatomical MRI for all patients at baseline. Error bars are 95% confidence intervals. MNI coordinates are shown for each slice as x, y, or z.