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Medication Overuse

Todd Schwedt, MD
Professor of Neurology
Mayo Clinic

The excessive use of migraine abortive medications, a.k.a. “medication overuse”, is common amongst people with frequent headaches. Approximately ½ of patients seen in headache specialty clinics have medication overuse and about ½ of people from the general population who have chronic migraine also have medication overuse. Medication overuse increases the risk of developing more frequent headaches, can cause medication overuse headache, and is associated with increased headache-related disability, medical expenses, and risks for medication side effects and toxicities.

This virtual issue highlights research, review, and editorial articles that have been published within the pages of Headache or Headache Currents that discuss the epidemiology and burden of medication overuse, its pathophysiologic mechanisms, and treatment approaches.

Epidemiology and Burden


Donnet A, Braunstein D, Pradel V, Sciortino V, Allaria-Lapierre V, Micallef J, Lanteri-Minet M. Ergot use and overuse: a pharmacoepidemiology retrospective cohort study. Headache 2016;56:547-554.


Amadio A, Lee K, Yao Z, Camacho X, Knowles S, Lay C, Paterson JM, Hunt J, Gomes T on behalf of the Ontario Drug Policy Research Network. Public drug coverage and its impact on triptan use across Canada: a population-based study. Headache 2015;55;S4: 212-220.

D’Amico D, Grazzi L, Bussone G, Curone M, Di Fiore P, Usai S, Leonardi M, Giovannetti AM, Schiavolin S, Raggi A. Are depressive symptomatology, self-efficacy, and perceived social support related to disability and quality of life in patients with chronic migraine associated to medication overuse? Data from a cross-sectional study. Headache 2015;55:636-645.


Shah AM, Bendtsen L, Zeeberg P, Jensen RH. Reduction of medication costs after detoxification for medication-overuse headache. Headache 2013;53:665-672.


Piazza F, Chiappedi M, Maffioletti E, Galli F, Balottin U. Medication overuse headache in school-aged children: more common than expected? Headache 2012;52:1506-1510.


Fontanillas N, Colas R, Munoz P, Oterino A, Pascual J. Long-term evolution of chronic daily headache with medication overuse in the general population. Headache 2010;50:981-988.

Pathophysiologic Mechanisms


Cargnin S, Pautasso C, Viana M, Sances G, Mittino D, Cantello R, Tassorelli C, Nappi G, Terrazzino S. Association of RAMP1 rs7590387 with the risk of migraine transformation into medication overuse headache. Headache 2015;55:658-668.

Lucchesi C, Baldacci F, Cafalli M, Chico L, Lo Gerfo A, Bonuccelli U, Siciliano G, Gori S. Headache 2015;55:984-991. Evidences of reduced antioxidant activity in patients with chronic migraine and medication-overuse headache. Headache 2015;55:984-991.


Biagianti B, Grazzi L, Gambini O, Usai S, Muffatti R, Scarone S, Bussone G. Orbitofrontal dysfunction and medication overuse in patients with migraine. Headache 2012;52:1511-1519.

Ferraro D, Vollono C, Miliucci R, Virdis D, De Armas L, Pazzaglia C, Le Pera D, Tarantino S, Balestri M, Di Trapani G, Valeriani M. Habituation to pain in “medication overuse headache”: a CO2 laser-evoked potential study. Headache 2012;52:792-807.

Ferraro S, Grazzi L, Muffatti R, Nava S, Ghielmetti F, Bertolino N, Mandelli ML, Visintin E, Bruzzone MG, Nigri A, Epifani F, Bussone G, Chiapparini L. In medication-overuse headache, fMRI shows long-lasting dysfunction in midbrain areas. Headache 2012;52:1520-1534.

Perrotta A, Arce-Leal N, Tassorelli C, Gasperi V, Sances G, Blandini F, Serrao M, Bolla M, Pierelli F, Nappi G, Maccarrone M, Sandrini G. Acute reduction of anandamide-hydrolase (FAAH) activity is coupled with a reduction of nociceptive pathways facilitation in medication-overuse headache subjects after withdrawal therapy. Headache 2012;52:1350-1361.

Robbins A, Schmitt D, Winterson BJ, Meng ID. Chronic morphine increases Fos-positive neurons after concurrent cornea and tail stimulation. Headache 2012;52:262-273.


Forcelini CM, Dantas DCM, Luz C, Santin R, Stein AT, Barros HMT, Barea LM. Analysis of leukocytes in medication-overuse headache, chronic migraine, and episodic migraine. Headache 2011;51:1228-1238.

Galli F, Pozzi G, Frustaci A, Allena M, Anastasi S, Chirumbolo A, Ghiotto N, Guidetti V, Matarrese A, Nappi G, Pazzi S, Quartesan R, Sances G, Tassorelli C. Differences in the personality profile of medication-overuse headache sufferers and drug addict patients: a comparative study using MMPI-2. Headache 2011;51:1212-1227.


Grazzi L, Chiapparini L, Ferraro S, Usai S, Andrasik F, Mandelli ML, Bruzzone MG, Bussone G. Chronic migraine with medication overuse pre-post withdrawal of symptomatic medication: clinical results and fMRI correlations. Headache 2010;50:998-1004.

Sances G, Galli F, Anastasi S, Ghiotto N, De Giorgio G, Guidetti V, Firenze C, Pazzi S, Quartesan R, Gallucci M, Nappi G. Medication-overuse headache and personality: a controlled study by means of the MMPI-2. Headache 2010;50:198-209.

Supornsilpchai W, Le Grand SM, Srikiatkhachorn A. Involvement of pro-nociceptive 5-HT2A receptor in the pathogenesis of medication-overuse headache. Headache 2010;50:185-197.

Terrazzino S, Sances G, Balsamo F, Viana M, Monaco F, Bellomo G, Martignoni E, Tassorelli C, Nappi G, Canonico PL, Genazzani AA. Role of 2 common variants of 5HT2A gene in medication overuse headache. Headache 2010;50:1587-1596.



Johnson JL, Kwok YH, Sumracki NM, Swift JE, Hutchinson MR, Johnson K, Williams DB, Tuke J, Rolan PE. Glial attenuation with ibudilast in the treatment of medication overuse headache: a double-blind, randomized, placebo-controlled pilot trial of efficacy and safety. Headache 2015;55:1192-1208.

Taghdiri F, Togha M, Jahromi SR, Paknejad SMH. Celecoxib vs. prednisone for the treatment of withdrawal headache in patients with medication overuse headache: a randomized, double-blind clinical trial. Headache 2015; 55:128-135.


Munksgaard SB, Bendtsen L, Jensen RH. Treatment-resistant medication overuse headache can be cured. Headache 2012; 52:1120-1129.


Trucco M, Meineri P, Ruiz L, Gionco M. Medication overuse headache: withdrawal and prophylactic therapeutic regimen. Headache 2010;50:989-997.

Education and Knowledge


Hedenrud T, Babic N, Jonsson P. Medication overuse headache: self-perceived and actual knowledge among pharmacy staff. Headache 2014;54:1019-1025.



Da Silva AN, Lake AE. Clinical aspects of medication overuse headaches. Headache 2014;54:211-217.

Munksgaard SB, Jensen RH. Medication overuse headache. Headache 2014;54:1251-1257.

Srikiatkhachorn A, Maneesri le Grand S, Supornsilpchai W, Storer RJ. Pathophysiology of medication overuse headache – an update. Headache 2014;54:204-210.


Radat F, Lanteri-Minet M. What is the role of dependence-related behavior in medication-overuse headache? Headache 2010;50:1597-1611.

Editorials and Letters


Munksgaard SB, Jensen RH. Medication overuse headache: inaccurate and overdiagnosed – a response. Headache 2015;55:206-207.


Robbins L. Medication overuse headache: inaccurate and overdiagnosed. Headache 2014;54:1656-1657.

Tepper SJ. Editorial- Chronic migraine and medication overuse headache. Headache 2014;54:1249-1250.


Cuvellier J-C, Nasser H, Vallee L. Medication overuse headache in school-aged children: more common than expected? Headache 2013;53:387-388.

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