Skip to content


The Journal of Headache and Pain

Official Journal of the "European Headache Federation" and of "Lifting The Burden - The Global Campaign against Headache"

The Journal of Headache and Pain Cover Image

Volume 16 Supplement 1

1st Joint ANIRCEF-SISC Congress

Open Access

P057. Prophylaxis with low-dose methadone in patients affected by daily refractory headache and medication-overuse headache: a prospective cohort study (METACEF study)

  • Chiara Lupi1Email author,
  • Chiara Pracucci2,
  • Francesco De Cesaris1,
  • Eleonora Rossi1,
  • Pierangelo Geppetti1,
  • Silvia Benemei1,
  • Valentina Galli2,
  • Brunella Occupati2,
  • Viola Mazzucco2 and
  • Guido Mannaioni2
Contributed equally
The Journal of Headache and Pain201516(Suppl 1):A118

Published: 28 September 2015


Visual Analogical ScaleTherapeutic OptionDrug ReactionAdverse Drug ReactionPain Intensity


To evaluate the effectiveness, safety, and tolerability of a 12-month treatment with low doses of methadone (MT) (mean MT dosage 12.3 mg ± SD 7.3) as prophylaxis in patients affected by daily refractory headache and medication-overuse headache.


Prospective cohort study.


Since May 3rd, 2012 up to January 8th, 2015, we enrolled 24 patients (18 females, 6 males; average age, 48 years) who were considered eligible to be treated with methadone. Nine patients dropped out because of adverse drug reactions (n=4, mean time of drop-out 7 days) or treatment ineffectiveness (n=5, mean time of drop-out 6 months). Six patients completed the 12-month treatment. After 1-year follow-up they still reported daily headache, however, they showed an impressive decrease of analgesic and/or antimigraine drug consumption (from 147.7 medications per month ± SD 124 to 8.5 medications per month ± SD 6.1) and a significant decrease of visual analogic scale (VAS) pain intensity (from 5.8 ± SD 2.6 to 2.8 ± SD 2.1). These patients were treated with daily methadone doses ranging from 5 mg to 60 mg; methadone dosages were safe and well tolerated.


In patients affected by daily refractory headache and medication-overuse headache, who are exposed to the risk of serious side effects due to prolonged analgesic and/or antimigraine treatment, prophylaxis with low-dose methadone therapy seems to represent an effective therapeutic option.

Written informed consent to publication was obtained from the patient(s).


Authors’ Affiliations

Headache Centre, Careggi University Hospital, University of Florence, Florence, Italy
Toxicology Unit, Careggi University Hospital, Florence, Italy


© Lupi et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Please note that comments may be removed without notice if they are flagged by another user or do not comply with our community guidelines.