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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)

Year of Publication: 2023

Authors: Grazzi L, D'Amico D, Guastafierro E, ..., Raggi A

Journal: The Journal of Headache and Pain

Citation: Grazzi et al. The Journal of Headache and Pain (2023) 24:86

Link: https://doi.org/10.1186/s10194-023-01630-0


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?

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

FieldControlTaU + Mindfulness (TaU+MIND)
N8988
InterventionInpatient/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
Duration12 months follow-up6-week intervention with 12 months follow-up

Outcomes

OutcomeTypeControlInterventionHR / OR / RRP-value
Achievement of ≥50% reduction in headache frequency at 12 months compared to baselinePrimary43/89 (48.3%)Reported as 78.4% in TaU+MIND group<0.0001
Secondary
Secondary
Secondary
Secondary
Secondary
Secondary
Secondary
Secondary
Safety
Safety
None reportedAdverse

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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