A randomized controlled trial of mindfulness-based stress reduction to prevent flare-up in patients with inactive ulcerative colitis

Abstract

Background/aims: The primary therapeutic goals in ulcerative colitis (UC) are to maintain excellent quality of life (QOL) by treating flare-ups when they occur, and preventing flare-ups. Since stress can trigger UC flare-ups, we investigated the efficacy of mindfulness-based stress reduction (MBSR) to reduce flare-ups and improve QOL.

Methods: Patients with moderately severe UC, in remission, were randomized to MBSR or time/attention control. Primary outcome was disease status. Secondary outcomes were changes in markers of inflammation and disease activity, markers of stress and psychological assessments.

Results: 55 subjects were randomized. Absence of flares, time to flare and severity of flare over 1 year were similar between the two groups. However, post hoc analysis showed that MBSR decreased the proportion of participants with at least one flare-up among those with top tertile urinary cortisol and baseline perceived stress (30 vs. 70%; p < 0.001). MBSR patients who flared demonstrated significantly lower stress at the last visit compared to flared patients in the control group (p = 0.04). Furthermore, MBSR prevented a drop in the Inflammatory Bowel Disease Quality of Life Questionnaire during flare (p < 0.01).

Conclusion: MBSR did not affect the rate or severity of flare-ups in UC patients in remission. However, MBSR might be effective for those with high stress reactivity (high perceived stress and urinary cortisol) during remission. MBSR appears to improve QOL in UC patients by minimizing the negative impact of flare-ups on QOL. Further studies are needed to identify a subset of patients for whom MBSR could alter disease course.

Trial registration: ClinicalTrials.gov NCT00568256.

Figure 1

Flow of randomzied subjects in Mindfulness Based Stress Reduction (MBSR) and control groups.

Figure 2

Kaplan-Meier Survival Analysis. Comparison of time to flare from baseline to last visit (flare-up). MBSR = Mindfulness Based Stress Reduction. Time to First Flare: as measured in number of days from baseline visit to flare-up

Figure 3

A subset of UC patients responded to MBSR treatment. (A & B) Inflammatory Bowel Disease Questionnaire (IBDQ)-Bowel Subscale. When all subjects were pooled together there were no significant differences between self-reported IBDDQ Bowel symptoms at baseline (BL) or during the last visit (LV) for subjects in the Control (A) or MBSR (B) groups (Student’s t-test: Control, p=0.262; MBSR, p=0.509). Separating subjects into tertiles based on the baseline IBDQ scores (i.e., those with the least severe / bottom tertile (blue), moderately severe / middle tertile (not shown), and most severe / top tertile (red)) revealed that patients with the most severe IBDQ-bowel symptoms at baseline responded positively to MBSR (B) an effect that was not observed in the Control group (A). (Two-way repeated measures ANOVA: Control, tertile F(1,31)=34.129, p<0.0001; visit F(1,31)=2.361, p=0.147; interaction F(1,31)=4.645, p=0.049. MBSR, tertile F(1,23)=16.456, p=0.002; visit F(1,23)=18.825, p=0.002; interaction F(1,23)=45.813, p<0.0001.) ** indicates post-hoc Tukey significance, p<0.01. (C) Perceived Stress Questionnaire (PSQ). When all subjects were pooled together, the percent of subjects that flared between Control (C) and MBSR (M) subjects was similar. Separating subjects into tertiles based on baseline PSQ scores suggests that those subjects with the highest perceived stress at baseline may have a reduction in flare, an effect that was not observed in the Control group. (D) Urinary Cortisol. When all subjects were pooled together, the percent of subjects that flared between Control (C) and MBSR (M) subjects was similar. Separating subjects into tertiles based on baseline urinary corisol suggests that those subjects with the physiological stress response at baseline may have a reduction in flare, an effect that was not observed in the Control group.