MIND-CM
Efficacy of mindfulness added to treatment as usual in patients with chronic migraine and medication overuse headache: a phase-III single-blind randomized-controlled trial (the MIND-CM study)
Clinical Question
Does adding a six-session mindfulness-based intervention to treatment as usual improve headache frequency and related outcomes in patients with chronic migraine and medication overuse headache?
Study Overview
Objective
To assess the efficacy of a six-session mindfulness-based treatment added to treatment as usual (TaU) versus TaU alone in patients with chronic migraine and medication overuse headache.
Study Summary
- Primary endpoint (≥50% headache frequency reduction at 12 months) achieved by 78.4% in TaU+MIND vs 48.3% in TaU alone (p<0.0001)
- TaU+MIND group showed superior improvements in headache frequency, quality of life, disability, headache impact, loss of productive time, and medication intake
- TaU+MIND reduced total, indirect, and direct healthcare costs compared to TaU alone
- No adverse events reported in either group
Intervention
Six weekly 90-minute group mindfulness sessions plus 7-10 minutes daily self-practice, added to standard treatment as usual (drug withdrawal, education, tailored prophylaxis).
Patients per Arm
TaU: 89; TaU+MIND: 88
Bottom Line
In patients with chronic migraine and medication overuse headache, adding a six-week mindfulness-based intervention with daily 7-10 minute self-practice to treatment as usual significantly increased the proportion achieving ≥50% headache frequency reduction at 12 months (78.4% vs 48.3%, p<0.0001) and improved quality of life, disability, medication intake, and disease costs.
Major Points
- Phase-III single-blind RCT of 177 patients with chronic migraine and medication overuse headache randomized 1:1 to TaU vs TaU + mindfulness
- Primary endpoint of ≥50% headache frequency reduction at 12 months was significantly higher with mindfulness add-on: 78.4% vs 48.3% (p<0.0001)
- TaU+MIND was superior across multiple secondary outcomes including QoL, disability, headache impact, productivity, and medication use
- Direct, indirect, and total healthcare costs were lower in the TaU+MIND group
- No adverse events reported; drop-out rates were similar between groups (~12-14%)
- Mindfulness intervention was a brief, 6-week program (90-minute weekly group sessions) plus brief daily home practice — practical to implement
Design
Study Type: Phase-III single-blind randomized-controlled trial
Randomization: 1
Blinding: Single-blind (evaluating neurologist blinded to allocation)
Allocation: 1:1 randomization using computer-generated list with opaque envelopes
Enrollment Period: November 2018 to December 2021
Follow-up Duration: 12 months (assessments at 3, 6, and 12 months)
Centers: 1
Countries: Italy
Sample Size: 177
Analyzed: 177
Analysis: Intention-to-treat for primary endpoint (Pearson's Chi-Squared with multiple imputation by chained equations); per-protocol linear mixed models for secondary endpoints
Power Calculation: Assuming 48% TaU response and 20% absolute increase with mindfulness, alpha 0.05, power 80%, 75 patients/group needed; 170 total to account for 12% loss to follow-up
Registration: ClinicalTrials.gov NCT03671681
Inclusion Criteria
- Diagnosis of both Chronic Migraine (ICHD-3 code 1.3) and Medication Overuse Headache (ICHD-3 code 8.2) with close temporal relation
- ≥15 headache days per month in the previous 3 months
- ≥8 days with migraine-like features per month
- Overuse of one or more classes of symptomatic medications
- Attending the specialty headache center for structured withdrawal treatment
Exclusion Criteria
- Psychiatric comorbidities of psychotic area
- Pregnancy
- Secondary headaches
- Withdrawal from MOH twice or more in the previous two years
- Any previous experience with mindfulness
Arms
| Field | Control | TaU + Mindfulness (TaU+MIND) |
|---|---|---|
| N | 89 | 88 |
| Intervention | Inpatient/day-hospital structured withdrawal of overused medications (5-8 days, IV hydration, IV steroids and ademetionine, oral steroids, benzodiazepines, IV methoclopramide/indomethacin if needed); patient education on proper acute medication use and lifestyle (exercise, hydration, regular meals, sleep hygiene); tailored prophylaxis (antiepileptics, antidepressants, antihypertensives, OnabotulinumtoxinA, CGRP monoclonal antibodies, nutraceuticals) | TaU plus six weekly 90-minute group mindfulness sessions (groups of 6-8 patients led by experienced instructor) focused on breathing, non-judgmental acceptance, recognition of internal states, and addressing pain-pill automatism; sessions progressed from 5 to 25 minutes; home practice 7-10 minutes daily using a 12-minute audio file |
| Duration | 12 months follow-up | 6-week intervention with 12 months follow-up |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Achievement of ≥50% reduction in headache frequency at 12 months compared to baseline | Primary | 43/89 (48.3%) | Reported as 78.4% in TaU+MIND group | ~30 percentage point absolute increase favoring TaU+MIND | <0.0001 |
| Headache frequency change (days and percentage) | Secondary | Superior improvement with TaU+MIND vs TaU | |||
| Quality of life (MSQ v2.1) | Secondary | Superior improvement with TaU+MIND | |||
| Disability (MIDAS, WHODAS-12) | Secondary | Superior improvement with TaU+MIND | |||
| Headache impact (HIT-6) | Secondary | Superior improvement with TaU+MIND | |||
| Loss of productive time (LPT) | Secondary | Superior improvement with TaU+MIND | |||
| Symptomatic medication intake (NSAIDs, triptans, total) | Secondary | Superior reduction with TaU+MIND | |||
| Total, indirect, and direct healthcare costs | Secondary | Lower in TaU+MIND group | |||
| Depression and anxiety (BDI-II, STAI-Y), cutaneous allodynia (ASC-12), self-awareness (MAAS), HEADWORK | Secondary | Assessed as secondary endpoints; full numeric details not in extracted abstract section | |||
| Adverse events | Safety | No adverse events reported in either group | |||
| Drop-out rate | Safety | TaU: 11/89 (12.4%); TaU+MIND: 12/88 (13.6%) | |||
| Total | Adverse | None reported | |||
Subgroup Analysis
Linear mixed models adjusted for age, sex, years of education, CM duration, working status, and previous withdrawal; clinically meaningful HIT-6 improvement (≥6 points) compared between groups using Pearson's Chi-Squared at 3, 6, and 12 months
Criticisms
- Single-center Italian specialty headache center may limit generalizability
- Single-blind design — patients aware of allocation could influence subjective outcomes
- Patients with prior mindfulness experience were excluded, limiting external validity
- COVID-19 pandemic required some assessments via tele-visit, potentially affecting data collection consistency
- Mindfulness instructor was also a study neurologist (L.G.), introducing potential performance bias
Based on: MIND-CM (The Journal of Headache and Pain, 2023)
Authors: Grazzi L, D'Amico D, Guastafierro E, ..., Raggi A
Citation: Grazzi et al. The Journal of Headache and Pain (2023) 24:86
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