Medication-overuse headache is defined as headache occurring on more than 15days in a month in people with pre-existing primary headache and developing as a consequence of regular overuse of acute headache treatments. Most patients have a background of migraine, which has slowly transformed over months and years from the episodic to chronic form; with this comes an increased use of acute migraine treatment. (Wakerly, 2019).
The prevalence usually ranges from 0.5 to 2.5 % in adults and is higher in tertiary care and headache referral centers, where up to 30 % of headache patients in Europe and 50 % in the USA have MOH. Women are affected more often than men, as well as in people with comorbid depression, anxiety, and other chronic pain conditions. MOH is most seen in those aged 40 to 45, but other age groups can be affected. Interestingly, patients with MOH are also more likely to have relatives who overuse drugs or have substance abuse problems, so a link between both conditions has been studied. (Cheung et al, 2015; Diener et al, 2019)
MOH patients have migraine or tension-type headache as their primary headache, usually episodic, that started in the second or third decades. In some subpopulations of patients, at around 30–40 years of age the headaches became more frequent with the time and lose typical features of migraine such as photophobia, osmophobia, phonophobia, and the gastrointestinal symptoms of nausea and vomiting. Other patients start with episodic migraine with aura, which evolves into attacks of migraine without aura and daily headache occur subsequently. Most patients may present a clear family history of migraine and keep intermittent full-blown migraine attacks with variable frequency. (Krymchantowski et al, 2020)
Certain features in MOH such as their compulsive drug-seeking behavior, withdrawal headaches and high relapse rates share similarities with drug dependence, suggesting that there might be common underlying biological and psychobehavioral mechanisms. Recent studies revealed similar decision-making impairment from a cognitive perspective, indicating the presence of a maladaptive reward system in both disorders. There is an increased familial risk for drug dependence and genetic association with dopaminergic and drug dependence molecular pathways in MOH. (Lau et al, 2020)
Results of single studies show a potential role of polymorphic variants of the dopaminergic gene system or of other genes related to drug-dependence pathways as susceptibility factors for disease or as determinants of monthly drug consumption, respectively. Despite a relevant number of candidate gene association studies having reported positive findings, unequivocal and definitive conclusions cannot be drawn due to some methodological flaws, including weak study design and lack of internal or external replication studies. (Cargnin et al, 2018)
Caffeine withdrawal produces headaches and may be related to weekend migraine attacks. 20 healthy volunteers without a headache history, underwent clinical evaluation. After 24 h of complete caffeine abstinence, 10 suffered from moderate to severe headaches with complete recovery within 1 h after caffeine intake. Chronic consumption of caffeine seems to increase the burden of migraine, but a protective effect as an acute treatment or in severely affected patients cannot be excluded. (Alstadhaug et al, 2019)
Excessive caffeine consumption induces a series of both acute and chronic biological and physiological changes that may give rise to cognitive decline, depression, fatigue, insomnia, cardiovascular changes, and headache. Chronic consumption of caffeine promotes a pro-nociceptive state of cortical hyperexcitability that can intensify a primary headache or trigger a headache due to excessive analgesic use. (Espinosa et al, 2017)
The evidence to support the early discontinuation of overused medications is low because of the lack of a control group in studies. For patients with chronic migraine (CM) and medication overuse (MO), there are large randomized control trials supporting the use of onabotulinumtoxinA and topiramate without early discontinuation; however the evidence is limited since data were obtained from post hoc analysis. Considering current available evidence and the systemic toxicity of overusing acute headache medication, discontinuation of the overused medication with the addition of preventive medication seems a logical choice. (Chiang et al, 2016)
Wakerley BR. Medication-overuse headache. Pract Neurol. 2019 Oct;19(5):399-403. doi: 10.1136/practneurol-2018-002048. Epub 2019 Jul 4. PMID: 31273078.
Cheung V, Amoozegar F, Dilli E. Medication overuse headache. Curr Neurol Neurosci Rep. 2015 Jan;15(1):509. doi: 10.1007/s11910-014-0509-x. PMID: 25398377.
Diener HC, Dodick D, Evers S, Holle D, Jensen RH, Lipton RB, Porreca F, Silberstein S, Schwedt T. Pathophysiology, prevention, and treatment of medication overuse headache. Lancet Neurol. 2019 Sep;18(9):891-902. doi: 10.1016/S1474-4422(19)30146-2. Epub 2019 Jun 4. PMID: 31174999.
Krymchantowski AV, Jevoux CC, Krymchantowski AG, Vivas RS, Silva-Néto R. Medication overuse headache: an overview of clinical aspects, mechanisms, and treatments. Expert Rev Neurother. 2020 Jun;20(6):591-600.
Lau CI, Liu MN, Chen WH, Walsh V, Wang SJ. Clinical and biobehavioral perspectives: Is medication overuse headache a behavior of dependence? Prog Brain Res. 2020;255:371-402. doi: 10.1016/bs.pbr.2020.05.019. Epub 2020 Jun 19. PMID: 33008514.
Cargnin S, Viana M, Sances G, Tassorelli C, Terrazzino S. A systematic review and critical appraisal of gene polymorphism association studies in medication-overuse headache. Cephalalgia. 2018 Jun;38(7):1361-1373. doi: 10.1177/0333102417728244. Epub 2017 Sep 4. PMID: 28870085.
Alstadhaug KB, Andreou AP. Caffeine and Primary (Migraine) Headaches-Friend or Foe? Front Neurol. 2019 Dec 3;10:1275. doi: 10.3389/fneur.2019.01275. PMID: 31849829; PMCID: PMC6901704.
Espinosa Jovel CA, Sobrino Mejía FE. Caffeine and headache: specific remarks. Neurologia. 2017 Jul-Aug;32(6):394-398. English, Spanish. doi: 10.1016/j.nrl.2014.12.016. Epub 2015 Feb 26. PMID: 25728949.
Chiang CC, Schwedt TJ, Wang SJ, Dodick DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016 Apr;36(4):371-86. doi: 10.1177/0333102415593088. Epub 2015 Jun 29. PMID: 26122645.