Medication overuse headache (MOH) is a very common and largely preventable disorder with considerable impacts on health care costs. In fact, the socioeconomic burden of MOH may be almost double that of chronic migraine.
MOH is comorbid with primary headache disorders, particularly chronic migraine, tension-type headache, and post-traumatic headache, and can result from the overuse of several different agents, including over the counter analgesics such as acetaminophen and NSAIDs, and prescription medications including opioids, barbiturates, and triptans. Chronic daily headache is estimated to have a prevalence of 3 to 4%, and some studies suggest that as many as 70% of patients with frequent headache take these medications on a near daily basis.1
The International Classification of Headache Disorders III (beta) defines MOH as a headache occurring on more than 15 days per month in a patient with a known headache disorder after the regular use of medication for more than 3 months.2
Many patients in this clinical setting will describe a change in pattern of their headache from their baseline, or else describe 2 types of headache: one that they will attribute to their pre-existing disorder and another that they will most typically deem a chronic daily headache. Notably, the chronic daily headache often does not fully meet criteria for their underlying primary headache diagnosis.
MOH can then be further sub-classified depending on the medication to which it can be attributed: ergotamine, triptans, simple analgesics, opiates, or multiple agents,2 however the amount of medication required for diagnosis differs slightly between agents.
Opiates, triptans, ergotamine, or combination overuse requires 10 days or more per month, whereas simple analgesic overuse (acetaminophen and NSAIDs) require 15 or more days per month. Additionally, if an individual is not overusing a single class of medication, but rather using multiple medications and the total combined use of all analgesics is greater than 10 days per month, then that also meets criteria for MOH. This denotes the importance of a detailed clinical history with a focus on how patients use non-prescription medications to help establish a proper diagnosis.
The pathophysiology of MOH is complex and incompletely understood. Our current understanding suggests increased neuronal excitability in the cerebral cortex and trigeminal system. The downstream effect is a higher likelihood for cortical spreading depression and central and peripheral sensitization.
Dysregulation of serotonergic pathways and altered expression of serotonin (5-HT) receptors, particularly 5-HT2A, have also been implicated. Lower 5-HT levels increase release of CGRP and lead to sensitization of nociceptors in the trigeminal system. The changes outlined above appear to reverse after cessation of the offending agent.3
The clinical phenotype of MOH appears to be quite similar, regardless of the offending agent and has characteristics which are similar to the underlying headache disorder. Additionally, MOH appears only to occur in patients with a pre-existing primary headache disorder.
For this reason, it is unlikely that the mechanisms of the offending medications are at fault for the clinical presentation of MOH, but rather it is the effect of the medication overuse on the underlying primary headache pathology.3
There appear to be both environmental and genetic risk factors for the development of MOH. Smoking and sedentary lifestyle are associated with a more than double risk of MOH.4 There is a clear association between psychiatric comorbidities such as anxiety and depression, but whether these are a cause or effect of MOH is not clear.5
Certain habits and underlying personality traits may also be risk factors. Specifically, cephalalgiaphobia, or the fear of headache may result in increased use of abortive medications leading to MOH.4 The use of caffeine, including the use of analgesics that contain caffeine, is also linked to the chronification of headache.6
Additionally, men and women may have different sensitivities to specific agents. Opiates appear to have a stronger relationship with MOH in men and barbiturates in women.5 Polymorphisms in the MTHFR,7 Dopamine Receptor D2 (DRD2),7 COMT,8 SLC6A4,8 and RAMP18 genes have all been linked with a higher likelihood of chronification of headache.
The treatment of medication overuse headache is often multifaceted and patient-dependent. The most important step is cessation of the offending agent or agents. Strategies for cessation of the medication at fault can differ depending on the medication class, duration, and dose being used by the patient.
Simple analgesics such as ASA, acetaminophen, and NSAIDs can typically be discontinued immediately. Likewise, triptans and ergotamines can be stopped immediately, and these patients may actually recover more quickly than other types of MOH. When opiate medications or barbiturates are implicated in MOH, cessation may require a prolonged taper and rarely inpatient detoxification. For more refractory cases, pain rehabilitation programs can also be beneficial.9
Upon cessation of the offending agent, additional treatment is usually required to bolster the effect, mitigate withdrawal symptoms, and increase compliance. In general, there are 2 strategies which are often used concurrently.
Some patients will require bridging therapy of a long-acting NSAID or short taper of an oral steroid which is started simultaneously with a longer term prophylactic agent .10 The most studied prophylactic agents in MOH are topiramate11 and onabotulinum toxin A,12 however other migraine prophylactic agents may be entirely appropriate depending on the patient.
Non-medication approaches such as biofeedback13 and cognitive behavioral therapy may be helpful adjunct therapies and may help with more long-term coping strategies.
The ultimate goal of treatment in MOH is to revert to a pattern of episodic headache more in keeping with the patient’s primary headache disorder. When an episodic pattern is achieved, it is paramount for the patient to have instruction in proper use of abortive medications to avoid recurrence.
Will Kingston, MD, completed his undergraduate degree in Biology at Queen’s University in Kingston, Ontario and attended medical school at Saba University School of Medicine in Saba, Netherlands Antilles. He completed his residency in neurology at the University of Toronto, where he served as chief resident. Dr Kingston is currently enrolled in a headache medicine fellowship at Mayo Clinic Arizona.
Rashmi Halker, MD, FAHS, is an Assistant Professor of Neurology at Mayo Clinic and a Fellow of the American Headache Society. She attended medical school at Wayne State University in Detroit before completing a residency in neurology and fellowship in headache medicine at Mayo Clinic in Phoenix, Arizona. Dr Halker is a headache medicine subspecialist at Mayo Clinic, and is also the chair of the Women’s Issues SIG for the American Headache Society.
The authors report no relevant disclosures.
- Westergaard ML, Gkumer C, Hansen EH, Jensen RH. Prevalence of chronic headache with and without medication overuse: Associations with socioeconomic position and physical and mental health status. Pain. 2014; 155:2005-2013.
- International Classification of Headache Disorders, 3rd edition (beta version). Cephalalgia. 2013; 33(9):629-808.
- Srikiatkhachorn A, le Grand SM, Supornsilpchai W, Storer RJ. Pathophysiology of Medication Overuse Headache – An Update. Headache. 2014; 54(1):204-210.
- Diener HS, Holle D, Solbach K, Gaul C. Medication-overuse headache: risk factors, pathophysiology and management. Nature Reviews. 2016; [Epub ahead of print]
- Cheung V, Amoozegar F, Dilli E. Medication Overuse Headache. Current Neurol Neurosci Rep. 2015; 15:509.
- Scher AI, Stewart WF, Lipton RB. Caffeine as a risk factor for chronic daily headache: a population-based study. Neurology. 2004; 63(11):2022-2027.
- Cargnin S, Viana M, Ghiotto N, et al. Functional polymorphisms in COMT and SLC6A4 genes influence the prognosis of patients with medication overuse headache after withdrawal therapy. Eur J Neurol. 2014; 21:989-995.
- Cargnin S, Pautasso C, Viana M, et al. Association of RAMP1 rs7590387 with the risk of migraine transformation into medication overuse headache. Headache. 2015; 55(5):6586-68
- Bruce BK, Townsend CO, Hooten WM, Moon JS, Swanson JW. Chronic pain rehabilitation in chronic headache disorders. Curr Pain Headache Rep. 2009; 13(1):67-72.
- Chiang CC, Schwedt T, Wang SJ, Dodick, DW. Treatment of medication-overuse headache: A systematic review. Cephalalgia. 2016; 36(4):371-386.
- Evers S, Jensen R. Treatment of medication overuse headache – guidelines of the EFNS headache panel. Eur J Neurol. 2011; 18(9):1115-1121.
- Sandini G, Perrotta A, Tassorelli C, et al. Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study. J Headache Pain. 2011; 12(4):427-433.
- Rausa M, Palomba D, Cevoli S, et al. Biofeedback in the prophylactic treatment of medication overuse headache: a pilot randomized controlled trial. J Headache Pain. 2016; 17(1):87.
This article originally appeared on Neurology Advisor