Materiały źródłowe

• #1 Medication-overuse headache: risk factors, pathophysiology and management | Nature Reviews Neurology

  https://www.nature.com/articles/nrneurol.2016.124

  Medication-overuse headache (MOH) headache worsening attributed to overuse of attack-aborting medication is common: its prevalence in the general population is 1%, and as high as 1170% in people with chronic daily headache. […] The pathophysiology of MOH is not completely understood, but headache seems to make the brain more susceptible to central sensitization; moreover, acute pain medications can interfere with neurotransmitter systems and thereby lead to MOH. […] Involvement of pro-nociceptive 5-HT2A receptor in the pathogenesis of medication-overuse headache. […] Chronic analgesic exposure on the central serotonin system: a possible mechanism of analgesic abuse headache. […] Medication-overuse headache: a worldwide problem.

• #2 Medication overuse headache – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/medication-overuse-headache-1.html

  Medication overuse headache is common, affecting at least 1% of the population. […] A high index of suspicion is warranted especially as there are no specific diagnostic tests. Withdrawal of the inciting medication(s) is the only effective treatment. […] Epidemiological data suggest that 4% of the population misuse pain medication, and that a minimum 1% of the general population in Europe, North America and Asia suffer from medication overuse headache. […] It is important that headaches due to overuse of medication are distinguished from those which are caused directly by medication, such as nitrates and related compounds. […] Medication overuse headache is estimated to be responsible for 30% of chronic daily headache, and accounts for 10-60% of patients attending specialist headache clinics.

• #3 Medication-Overuse Headache – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538150/

  Medication-overuse headaches (MOH), also known as analgesic rebound headaches, drug-induced headaches, or medication-misuse headaches, are a common neurologic disorder that results in enormous disability and suffering and plays a significant role in the transformation from episodic to chronic headache disorders. […] Medication overuse headache is classified as a secondary headache or chronic headache syndrome in the latest version of ICHD-3 (2018) under subsection 8.2 as a chronic headache disorder secondary to a pre-existing headache syndrome. […] The pathophysiology of MOH is not well understood, but studies have demonstrated that central sensitization likely plays a major role. […] The condition exhibits both functional and structural changes in the central nervous system (CNS), particularly the hippocampal periaqueductal gray area, posterior cingulate cortex thalamus, cerebellum, and orbitofrontal cortex (OFC), and the mesocorticolimbic reward system.

• #4 Frontiers | Medication overuse headache: a review of current evidence and management strategies

  https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1194134/full

  Medication overuse headache (MOH) is a common, challenging, and disabling condition that affects millions of people worldwide. MOH occurs when people who suffer from primary headaches, such as migraines or tension-type headaches, use painkillers too frequently or in excessive doses. This paradoxically leads to a worsening of headache frequency and severity. […] The precise pathophysiology of MOH remains uncertain. However, research shows that central sensitization has a major role. An expansion of the receptive nociceptive field, a decreased nociceptive threshold, and decreased noxious inhibitory control have been reported following chronic analgesic use. […] The frequent use of headache abortive medications is also thought to deplete 5-hydroxytryptamine (5-HT) in the central nervous system (CNS). This depletion leads to hyperexcitability in the cerebral cortex, potentially causing cortical spreading depression, as well as in the trigeminal system, which leads to increased sensitivity in both peripheral and central pain pathways. Reduced 5-HT levels also cause the trigeminal ganglia to release calcitonin gene-related peptide (CGRP), a peptide involved in pain transmission, which contributes to the sensitization of nociceptive trigeminal neurons.

• #5 Medication-Overuse Headache

  https://practicalneurology.com/diseases-diagnoses/headache-pain/medication-overuse-headache/30281/

  Alteration of cortical activity, central sensitization of the nociceptive trigeminal system, and changes in serotonin and dopamine expression and cannabinoid and calcitonin gene-related peptide receptors have all been considered as potential pathways for MOH. MOH produces central sensitization with structural and functional changes in the trigeminal nucleus caudalis, resulting in a decrease in the pain threshold and an increase in receptive fields.

• #6 Medication-Overuse Headache: Update on Management

  https://www.mdpi.com/2075-1729/14/9/1146

  Increased central sensitization of trigeminal nociceptive pathways: Animal experiments provide evidence of structural and functional alterations following chronic analgesic use including the upregulation of neuropeptides involved in the transmission of pain (CGRP, substance P, and nitric oxide synthase) in trigeminal ganglia; the expansion of receptive fields, and the decreased nociceptive threshold of central trigeminal neurons. […] Increased peripheral trigeminal sensitization: Peripheral trigeminal sensitization of nociceptors in perivascular areas may play a role in MOH. […] Increased cortical excitability: Cortical excitability is associated with the cortical spreading depression (CSD) that accompanies migraine aura and leads to the increased sensitivity of the trigeminal pain pathway.

• #7 Frontiers | Medication overuse headache: a review of current evidence and management strategies

  https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1194134/full

  Medication overuse headache (MOH) is a common, challenging, and disabling condition that affects millions of people worldwide. MOH occurs when people who suffer from primary headaches, such as migraines or tension-type headaches, use painkillers too frequently or in excessive doses. This paradoxically leads to a worsening of headache frequency and severity. […] The precise pathophysiology of MOH remains uncertain. However, research shows that central sensitization has a major role. An expansion of the receptive nociceptive field, a decreased nociceptive threshold, and decreased noxious inhibitory control have been reported following chronic analgesic use. […] The frequent use of headache abortive medications is also thought to deplete 5-hydroxytryptamine (5-HT) in the central nervous system (CNS). This depletion leads to hyperexcitability in the cerebral cortex, potentially causing cortical spreading depression, as well as in the trigeminal system, which leads to increased sensitivity in both peripheral and central pain pathways. Reduced 5-HT levels also cause the trigeminal ganglia to release calcitonin gene-related peptide (CGRP), a peptide involved in pain transmission, which contributes to the sensitization of nociceptive trigeminal neurons.

• #8 Medication-Overuse Headache – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538150/

  Medication-overuse headaches (MOH), also known as analgesic rebound headaches, drug-induced headaches, or medication-misuse headaches, are a common neurologic disorder that results in enormous disability and suffering and plays a significant role in the transformation from episodic to chronic headache disorders. […] Medication overuse headache is classified as a secondary headache or chronic headache syndrome in the latest version of ICHD-3 (2018) under subsection 8.2 as a chronic headache disorder secondary to a pre-existing headache syndrome. […] The pathophysiology of MOH is not well understood, but studies have demonstrated that central sensitization likely plays a major role. […] The condition exhibits both functional and structural changes in the central nervous system (CNS), particularly the hippocampal periaqueductal gray area, posterior cingulate cortex thalamus, cerebellum, and orbitofrontal cortex (OFC), and the mesocorticolimbic reward system.

• #9 Medication-overuse headache: clinical profile and management strategies | Neurosciences Journal

  https://nsj.org.sa/content/28/1/13

  Increased gray matter volume mainly in the periaqueductal grey area, hippocampus, posterior cingulate cortex, thalamus, cerebellum, fusiform gyrus, and ventral striatum. […] The character of MOH is difficult to differentiate from other forms of chronic daily headache. […] An interaction between susceptible patient and a therapeutic medication used excessively is considered MOH.

• #10 Medication-overuse headache: a widely recognized entity amidst ongoing debate | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0875-x

  Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. […] The underlying consensus for the entity of medication-overuse headache (MOH) consists of a deterioration of a pre-existing headache syndrome whilst overusing one or several types of acute painkilling treatments. […] Debates on the pathophysiological mechanisms, definitions of overuse and the nosology of MOH are ongoing. […] A complete understanding of the pathophysiology of MOH currently does not exist. […] Although the clinical aspects of MOH seem to be ambivalent, there is evidence for specific neurobiological aspects in MOH-models. […] Research shows that central sensitization has a major role in the pathophysiology of MOH. […] The serotonergic modulating system is presumably affected by chronic analgesic use, resulting in neuronal hyperexcitability, enhanced CSD and trigeminal nociception, caused by increased expression of pro-nociceptive serotonin 2A (5HT-2A) receptor binding sites and a decrease in the production of serotonin in the CNS.

• #11 Medication overuse headache | MedLink Neurology

  https://www.medlink.com/articles/medication-overuse-headache

  Medication overuse headache is a chronic headache that occurs in people with a preexisting primary headache, such as migraine or tension-type headache, following overuse of any kind of acute headache medication. […] Overuse of acute headache medications can lead to the development of medication overuse headache. […] The pathophysiology of medication overuse headache still remains unclear. […] The number of animal studies has increased significantly. Reuter and colleagues demonstrated that chronic exposure of triptans causes a down-regulation of receptors in trigeminal ganglion and, subsequently, a reduction of receptor function. […] Chronic administration of sumatriptan and zolmitriptan caused a decrease of the 5-HT synthesis in the dorsal raphe nuclei of the brainstem. […] Triptan given daily resulted in a sensitization of trigeminal nociception, possibly due to increased expression of neuronal nitric oxide synthase in dural afferents.

• #12 Medication-overuse headache: a widely recognized entity amidst ongoing debate | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0875-x

  Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. […] The underlying consensus for the entity of medication-overuse headache (MOH) consists of a deterioration of a pre-existing headache syndrome whilst overusing one or several types of acute painkilling treatments. […] Debates on the pathophysiological mechanisms, definitions of overuse and the nosology of MOH are ongoing. […] A complete understanding of the pathophysiology of MOH currently does not exist. […] Although the clinical aspects of MOH seem to be ambivalent, there is evidence for specific neurobiological aspects in MOH-models. […] Research shows that central sensitization has a major role in the pathophysiology of MOH. […] The serotonergic modulating system is presumably affected by chronic analgesic use, resulting in neuronal hyperexcitability, enhanced CSD and trigeminal nociception, caused by increased expression of pro-nociceptive serotonin 2A (5HT-2A) receptor binding sites and a decrease in the production of serotonin in the CNS.

• #13 A Descriptive Review of Medication-Overuse Headache: From Pathophysiology to the Comorbidities

  https://www.mdpi.com/2076-3425/13/10/1408

  In MOH, the activity of the serotonergic pain modulation system is impaired, with reduced production of serotonin in the CNS and increased expression of the pronociceptive serotonin receptor (5HT-2A). […] Central sensitization plays a key role in the pathophysiology of chronic migraine. Analysis of somatosensory evoked potentials has shown that patients with chronic migraine have cortical hyperexcitability compared to healthy controls and patients with episodic migraine. […] The numerous structural and functional changes in the nociceptive system observed in the studies conducted suggest that there is a neurobiological basis for MOH.

• #14 Medication-overuse headache: a widely recognized entity amidst ongoing debate | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0875-x

  Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. […] The underlying consensus for the entity of medication-overuse headache (MOH) consists of a deterioration of a pre-existing headache syndrome whilst overusing one or several types of acute painkilling treatments. […] Debates on the pathophysiological mechanisms, definitions of overuse and the nosology of MOH are ongoing. […] A complete understanding of the pathophysiology of MOH currently does not exist. […] Although the clinical aspects of MOH seem to be ambivalent, there is evidence for specific neurobiological aspects in MOH-models. […] Research shows that central sensitization has a major role in the pathophysiology of MOH. […] The serotonergic modulating system is presumably affected by chronic analgesic use, resulting in neuronal hyperexcitability, enhanced CSD and trigeminal nociception, caused by increased expression of pro-nociceptive serotonin 2A (5HT-2A) receptor binding sites and a decrease in the production of serotonin in the CNS.

• #15

• #16 Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5697138/

  Medication overuse headache (MOH) is a clinical concern in the management of migraine headache. MOH arises from the frequent use of medications used for the treatment of a primary headache. Medications that can cause MOH include opioid analgesics as well as formulations designed for the treatment of migraine, such as triptans, ergot alkaloids, or drug combinations that include caffeine and barbiturates. […] Gathering evidence indicates that migraine patients are more susceptible to development of MOH, and that prolonged use of these medications increases the prognosis for development of chronic migraine, leading to the suggestion that similar underlying mechanisms may drive both migraine headache and MOH. […] Increased CGRP levels in the blood have been linked to migraine and elevated CGRP can be caused by prolonged sumatriptan exposure. Possible mechanisms that may be common to both migraine and MOH include increased endogenous facilitation of pain and/or diminished endogenous pain inhibition.

• #17 Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5697138/

  Medication overuse headache (MOH) is a clinical concern in the management of migraine headache. MOH arises from the frequent use of medications used for the treatment of a primary headache. Medications that can cause MOH include opioid analgesics as well as formulations designed for the treatment of migraine, such as triptans, ergot alkaloids, or drug combinations that include caffeine and barbiturates. […] Gathering evidence indicates that migraine patients are more susceptible to development of MOH, and that prolonged use of these medications increases the prognosis for development of chronic migraine, leading to the suggestion that similar underlying mechanisms may drive both migraine headache and MOH. […] Increased CGRP levels in the blood have been linked to migraine and elevated CGRP can be caused by prolonged sumatriptan exposure. Possible mechanisms that may be common to both migraine and MOH include increased endogenous facilitation of pain and/or diminished endogenous pain inhibition.

• #18 A Descriptive Review of Medication-Overuse Headache: From Pathophysiology to the Comorbidities

  https://www.mdpi.com/2076-3425/13/10/1408

  Functional neuroimaging studies have revealed structural and functional abnormalities in various structures responsible for processing painful stimuli and in structures that provide the neurobiological basis of affective and addictive behaviors, such as the mesolimbic system. […] While cessation of excessive medication use leads to a loss of these changes in some patients, they persist long-term in others. This is understood as a kind of predisposition to the development of medication overuse. […] Experimental studies have shown that chronic exposure to sumatriptan leads to a reduction in the stimulus threshold and a sustained increase in the likelihood of cortical depolarization. Increased production of CGRP, substance P, and NO in the trigeminal ganglion has been demonstrated in MOH, characterized by a reduction in the nociceptive threshold and inhibitory mechanisms.

• #19 Frontiers | Medication overuse headache: a review of current evidence and management strategies

  https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1194134/full

  Medication overuse headache (MOH) is a common, challenging, and disabling condition that affects millions of people worldwide. MOH occurs when people who suffer from primary headaches, such as migraines or tension-type headaches, use painkillers too frequently or in excessive doses. This paradoxically leads to a worsening of headache frequency and severity. […] The precise pathophysiology of MOH remains uncertain. However, research shows that central sensitization has a major role. An expansion of the receptive nociceptive field, a decreased nociceptive threshold, and decreased noxious inhibitory control have been reported following chronic analgesic use. […] The frequent use of headache abortive medications is also thought to deplete 5-hydroxytryptamine (5-HT) in the central nervous system (CNS). This depletion leads to hyperexcitability in the cerebral cortex, potentially causing cortical spreading depression, as well as in the trigeminal system, which leads to increased sensitivity in both peripheral and central pain pathways. Reduced 5-HT levels also cause the trigeminal ganglia to release calcitonin gene-related peptide (CGRP), a peptide involved in pain transmission, which contributes to the sensitization of nociceptive trigeminal neurons.

• #20 Medication-overuse headache: a narrative review | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01755-w

  The mesocorticolimbic dopamine circuit, which is known to be altered in addiction, was studied in MOH patients by focusing on the ventromedial prefrontal cortex and substantia nigra/ ventral tegmental area complex, showing a dysfunction compared to controls and chronic migraine patients without medication overuse. […] The development of gepants, CGRP receptor antagonists, for the preventive treatment of migraine offers an important advance since if these medicines, useful also for acute treatment do not cause MOH, this would be a crucial advance.

• #21

• #22 Medication-overuse headache: clinical profile and management strategies | Neurosciences Journal

  https://nsj.org.sa/content/28/1/13

  Medication-overuse headache (MOH) is a disabling secondary headache disorder, with challenging consequences for affected patients and health care resources. […] New advances in headache neurosciences and development of new treatment options specific for headache, along with an understanding of the clinical profile and pathophysiological mechanisms of MOH, can help improve patient outcomes and decrease the burden on the health care system. […] The pathophysiology of MOH is still not fully understood. […] In animal studies, Green et al observed multiple changes in the physiological process in the central nervous system (CNS) after repetitive administration of analgesics. […] Data showed using triptans for long durations can result in susceptibility to cortical spreading depression (CSD) due to decreased threshold.

• #23 Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5697138/

  As migraineurs are most susceptible to development of MOH, some common neural mechanisms between migraine and MOH might be expected. A review of migraine mechanisms and neuroplastic changes that occur with chronic medication exposure reveals considerable overlap between the two. […] Prolonged exposure to analgesics may lead to MOH through the up-regulation of neural regulators of vasodilation and neurogenic inflammation. […] Recent studies have begun to examine the effect of prolonged exposure to triptans in initiating peripheral neuroplasticity that may promote headache. […] Evidence from observational, prospective clinic-based, case-control, and population-based studies indicates that the frequent use of acute medications to treat migraine headache, in a substantial subgroup of individuals, leads to the progression of migraine from an episodic disorder to a syndrome of daily or near daily migraine. The risk of and time to progression, the phenotype of the daily headache, and the duration of withdrawal symptoms appears to vary based on the acute medication and its frequency of use. These features, together with the unique and selective vulnerability of migraine patients to this phenomena, highlights the possibility that the mechanism(s) by which acute medications lead to this progression may differ depending on the particular drug, and may be similar to the underlying biology of acute attacks of migraine. […] Preclinical studies have now provided evidence for several potential mechanisms for the development of MOH, including increases in evoked CSD, a possible role for neurogenic inflammation, peripheral and central sensitization, and descending facilitation.

• #24 A Descriptive Review of Medication-Overuse Headache: From Pathophysiology to the Comorbidities

  https://www.mdpi.com/2076-3425/13/10/1408

  In MOH, the activity of the serotonergic pain modulation system is impaired, with reduced production of serotonin in the CNS and increased expression of the pronociceptive serotonin receptor (5HT-2A). […] Central sensitization plays a key role in the pathophysiology of chronic migraine. Analysis of somatosensory evoked potentials has shown that patients with chronic migraine have cortical hyperexcitability compared to healthy controls and patients with episodic migraine. […] The numerous structural and functional changes in the nociceptive system observed in the studies conducted suggest that there is a neurobiological basis for MOH.

• #25 Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5697138/

  As migraineurs are most susceptible to development of MOH, some common neural mechanisms between migraine and MOH might be expected. A review of migraine mechanisms and neuroplastic changes that occur with chronic medication exposure reveals considerable overlap between the two. […] Prolonged exposure to analgesics may lead to MOH through the up-regulation of neural regulators of vasodilation and neurogenic inflammation. […] Recent studies have begun to examine the effect of prolonged exposure to triptans in initiating peripheral neuroplasticity that may promote headache. […] Evidence from observational, prospective clinic-based, case-control, and population-based studies indicates that the frequent use of acute medications to treat migraine headache, in a substantial subgroup of individuals, leads to the progression of migraine from an episodic disorder to a syndrome of daily or near daily migraine. The risk of and time to progression, the phenotype of the daily headache, and the duration of withdrawal symptoms appears to vary based on the acute medication and its frequency of use. These features, together with the unique and selective vulnerability of migraine patients to this phenomena, highlights the possibility that the mechanism(s) by which acute medications lead to this progression may differ depending on the particular drug, and may be similar to the underlying biology of acute attacks of migraine. […] Preclinical studies have now provided evidence for several potential mechanisms for the development of MOH, including increases in evoked CSD, a possible role for neurogenic inflammation, peripheral and central sensitization, and descending facilitation.

• #26 Medication-overuse headache: a narrative review | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01755-w

  The current International Classification of Headache Disorders-3 (ICHD-3) includes MOH as a separate secondary disorder, described as headache occurring on 15 or more days/month for at least three months in a patient with a pre-existing headache disorder as a consequence of overuse of acute symptomatic medication. […] Indeed, a longitudinal study revealed that patients with episodic migraine were more likely to progress to chronic migraine if they were taking medication containing opioids or barbiturates, suggesting a medication-dependent effect. […] A study of Wilkinson and colleagues explored whether overuse of opiates (sic.) induces chronic daily headache in those with migraine who were post colectomy for ulcerative colitis for at least 1 year prior. […] The authors suggested that MOH may share some neurophysiological features with addiction.

• #27 Medication-overuse headache: a narrative review | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01755-w

  The mesocorticolimbic dopamine circuit, which is known to be altered in addiction, was studied in MOH patients by focusing on the ventromedial prefrontal cortex and substantia nigra/ ventral tegmental area complex, showing a dysfunction compared to controls and chronic migraine patients without medication overuse. […] The development of gepants, CGRP receptor antagonists, for the preventive treatment of migraine offers an important advance since if these medicines, useful also for acute treatment do not cause MOH, this would be a crucial advance.

• #28 Medication-overuse headache: clinical profile and management strategies | Neurosciences Journal

  https://nsj.org.sa/content/28/1/13

  Long-term exposure to analgesics was found to increase the neuronal excitability in the amygdala’s central nucleus, which may lead to the development of depression or anxiety. […] The serotonergic system was also affected by the use of analgesics for a long time, which leading to neuronal hyperexcitability, trigeminal nociception enhancement, and CSD due to an increase in the expression of serotonin 2A (pro-nociceptive) receptor binding sites and lowering of the production of serotonin in the CNS. […] Data from a study reported by Cargnin et al showed variations in genes in the dopaminergic gene system (DRD2, DRD4, SLC6A3), and genes related to dependence of drug pathways (ACE, HDAC3, WSF1, BDNF). […] Data from Pellesi et al have reported the detection of high concentrations of different serum bands in patients with MOH in comparison to controls.

• #29 Medication overuse headache – Wikipedia

  https://en.wikipedia.org/wiki/Medication_overuse_headache

  In some cases, individuals may be genetically predisposed to developing medication overuse headache. […] A PET study in patients with chronic analgesic overuse showed decreased activity in the orbitofrontal cortex of the brain, which is also seen in substance abuse. This suggests that there may be an underlying neurological susceptibility to addiction in some individuals. However, more research is needed to fully understand the complex interplay of factors that contribute to the development of MOH.

• #30 8.2 Medication-overuse headache (MOH) – ICHD-3

  https://ichd-3.org/8-headache-attributed-to-a-substance-or-its-withdrawal/8-2-medication-overuse-headache-moh/

  Headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped. […] 8.2 Medication-overuse headache is an interaction between a therapeutic agent used excessively and a susceptible patient. Among those with a previous primary headache diagnosis, most have 1. Migraine or 2. Tension-type headache (or both); only a small minority have other primary headache disorders such as 3.3 Chronic cluster headache or 4.10 New daily persistent headache. […] The diagnosis of 8.2 Medication-overuse headache is extremely important clinically. Epidemiological evidence from many countries indicates that more than half of people with headache on 15 or more days/month have 8.2 Medication-overuse headache. Clinical evidence shows that the majority of patients with this disorder improve after discontinuation of the overused medication, as does their responsiveness to preventative treatment. Simple advice on the causes and consequences of 8.2 Medication-overuse headache is an essential part of its management and can be provided with success in primary care. […] The behaviour of some patients with 8.2 Medication-overuse headache is similar to that seen with other drug addictions, and the Severity of Dependence Scale (SDS) score is a significant predictor of medication overuse among headache patients.

• #31 Medication-Overuse Headache – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538150/

  Also found were changes in the serotonergic neuromodulatory system, upregulation of vasoactive and pro-inflammatory mediators, increased susceptibility to cortical spreading depression, central sensitization, and an increase in nociceptive sensory fields. […] Some studies have theorized a potential genetic risk as to the etiology of the development of MOH. […] The primary force leading to MOH-related structural and functional properties of the brain seems to be prolonged exposure to pain medications.

• #32 Medication-overuse headache: clinical profile and management strategies | Neurosciences Journal

  https://nsj.org.sa/content/28/1/13

  Long-term exposure to analgesics was found to increase the neuronal excitability in the amygdala’s central nucleus, which may lead to the development of depression or anxiety. […] The serotonergic system was also affected by the use of analgesics for a long time, which leading to neuronal hyperexcitability, trigeminal nociception enhancement, and CSD due to an increase in the expression of serotonin 2A (pro-nociceptive) receptor binding sites and lowering of the production of serotonin in the CNS. […] Data from a study reported by Cargnin et al showed variations in genes in the dopaminergic gene system (DRD2, DRD4, SLC6A3), and genes related to dependence of drug pathways (ACE, HDAC3, WSF1, BDNF). […] Data from Pellesi et al have reported the detection of high concentrations of different serum bands in patients with MOH in comparison to controls.

• #33 Medication-overuse headache: clinical profile and management strategies | Neurosciences Journal

  https://nsj.org.sa/content/28/1/13

  Long-term exposure to analgesics was found to increase the neuronal excitability in the amygdala’s central nucleus, which may lead to the development of depression or anxiety. […] The serotonergic system was also affected by the use of analgesics for a long time, which leading to neuronal hyperexcitability, trigeminal nociception enhancement, and CSD due to an increase in the expression of serotonin 2A (pro-nociceptive) receptor binding sites and lowering of the production of serotonin in the CNS. […] Data from a study reported by Cargnin et al showed variations in genes in the dopaminergic gene system (DRD2, DRD4, SLC6A3), and genes related to dependence of drug pathways (ACE, HDAC3, WSF1, BDNF). […] Data from Pellesi et al have reported the detection of high concentrations of different serum bands in patients with MOH in comparison to controls.

• #34 A Descriptive Review of Medication-Overuse Headache: From Pathophysiology to the Comorbidities

  https://www.mdpi.com/2076-3425/13/10/1408

  Medication-overuse headache (MOH) is a secondary headache that is classified by the third edition of the International Classification of Headache Disorders as a group of headaches attributable to the administration or discontinuation of various substances. MOH occurs more than 15 days per month in patients with preexisting headaches. It occurs as a result of regular (at least 3 consecutive months) overuse (10 or 15 days, depending on the type of medication) of drugs used as acute or symptomatic headache therapy. […] The pathophysiology of medication-overuse headaches (MOHs) is not fully understood. In addition to factors related to previous headaches, psychological factors, personality traits, and a genetic predisposition play important roles. Genes involved in complex processes of endogenous pain modulation, drug metabolism, and the serotonin and dopamine systems have been linked to the development of MOH. Excessive use of analgesics leads to facilitation of supraspinal pain transmission.

• #35 S5:Ep12 – Understanding Medication Overuse Headache (Rebound Headache) – Association of Migraine Disorders

  https://www.migrainedisorders.org/podcast/s5ep12-understanding-medication-overuse-headache-rebound-headaches/

  But the exact underlying mechanisms for medication-overuse headaches are not fully understood. But there are several hypotheses. It’s believed that medication overuse can affect the neural pathways involved in a primary headache disorder, particularly in those occurring with migraines. Genetic factors may play a role. Certain gene variations are associated with metabolic abnormalities. We call them like serotonergic, dopaminergic transmissions. They kind of involved in the processing of chemicals. And even pathways involved in drug dependence have been involved in this headache. […] We have also looked at neuroimaging studies, and these studies have shown that there are structural and functional, even metabolic changes in the brains of individuals with medication-overuse headaches. And specific areas, for example, of the brain, like we call them, they’re involved in the pain processing and also in emotional control of the pain, like hippocampus, periaqueductal gray, we call it thalamus, cerebellum, cingulate cortex. Those areas, interestingly, are showing alterations in patients with medication-overuse headache.

• #36 Medication-Overuse Headache

  https://practicalneurology.com/diseases-diagnoses/headache-pain/medication-overuse-headache/30281/

  Medication-overuse headache (MOH) is a pattern of chronic daily headaches, in a patient with a pre-existing headache condition, caused by regular and excessive use of symptomatic and acute headache medications for 3 months or more. It is a secondary disorder in that it is caused by the very medications a patient uses to treat his or her headaches. […] It is unclear whether MOH is a consequence of living with chronic daily headache or the reverse, but it is clear that withdrawal of the overused drug(s) bring(s) relief to the majority of patients, suggesting a causative role for the medications. However, not everyone with medication overuse develops MOH. As the mechanism of action for the overused drugs differs from one another, it is unlikely that MOH is caused by a specific action of any of these drugs. As pre-existing headaches seem to be required for MOH to develop (daily use of these drugs for other conditions does not cause MOH), there seems to be a relationship between the pre-existing headache mechanism or pain pathway and MOH. However, the nature of those mechanisms for activating pain pathways is not yet fully understood.

• #37 Medication overuse headache | MedLink Neurology

  https://www.medlink.com/articles/medication-overuse-headache

  Medication overuse headache is a chronic headache that occurs in people with a preexisting primary headache, such as migraine or tension-type headache, following overuse of any kind of acute headache medication. […] Overuse of acute headache medications can lead to the development of medication overuse headache. […] The pathophysiology of medication overuse headache still remains unclear. […] The number of animal studies has increased significantly. Reuter and colleagues demonstrated that chronic exposure of triptans causes a down-regulation of receptors in trigeminal ganglion and, subsequently, a reduction of receptor function. […] Chronic administration of sumatriptan and zolmitriptan caused a decrease of the 5-HT synthesis in the dorsal raphe nuclei of the brainstem. […] Triptan given daily resulted in a sensitization of trigeminal nociception, possibly due to increased expression of neuronal nitric oxide synthase in dural afferents.

• #38 Medication overuse headache | MedLink Neurology

  https://www.medlink.com/articles/medication-overuse-headache

  Medication overuse headache is a chronic headache that occurs in people with a preexisting primary headache, such as migraine or tension-type headache, following overuse of any kind of acute headache medication. […] Overuse of acute headache medications can lead to the development of medication overuse headache. […] The pathophysiology of medication overuse headache still remains unclear. […] The number of animal studies has increased significantly. Reuter and colleagues demonstrated that chronic exposure of triptans causes a down-regulation of receptors in trigeminal ganglion and, subsequently, a reduction of receptor function. […] Chronic administration of sumatriptan and zolmitriptan caused a decrease of the 5-HT synthesis in the dorsal raphe nuclei of the brainstem. […] Triptan given daily resulted in a sensitization of trigeminal nociception, possibly due to increased expression of neuronal nitric oxide synthase in dural afferents.

• #39 Medication overuse headache | MedLink Neurology

  https://www.medlink.com/articles/medication-overuse-headache

  Medication overuse headache is a chronic headache that occurs in people with a preexisting primary headache, such as migraine or tension-type headache, following overuse of any kind of acute headache medication. […] Overuse of acute headache medications can lead to the development of medication overuse headache. […] The pathophysiology of medication overuse headache still remains unclear. […] The number of animal studies has increased significantly. Reuter and colleagues demonstrated that chronic exposure of triptans causes a down-regulation of receptors in trigeminal ganglion and, subsequently, a reduction of receptor function. […] Chronic administration of sumatriptan and zolmitriptan caused a decrease of the 5-HT synthesis in the dorsal raphe nuclei of the brainstem. […] Triptan given daily resulted in a sensitization of trigeminal nociception, possibly due to increased expression of neuronal nitric oxide synthase in dural afferents.

• #40 Medication overuse headache – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/medication-overuse-headache-1.html

  At least some of the characteristics of medication overuse headache may be understood by considering the mechanism of action. […] Triptan usage therefore results in tachyphylaxis (less effect for the same dosage) more quickly, at a lower frequency of use, and at a lower dosage than other non-narcotic analgesics. […] Receptor and enzyme downregulation in structures responsible for the transmission and reception of nociceptive input creates increased sensitivity to such input, resulting in a lowered threshold for pain perception. […] The essential treatment of medication overuse headache is withdrawal of the offending medication, but in most cases that is easier said than done. […] Following successful withdrawal of the overused medication, migraine prophylaxis, careful assessment of precipitants, counselling, a headache management plan and clear limits on the use of analgesia may all be required in order to prevent relapse. […] The prevalence of medication overuse headache is high and the condition is usually present for a long time before it is recognised and treated.

• #41 Medication overuse headaches – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/medication-overuse-headache/symptoms-causes/syc-20377083

  Your risk goes up if you use combined painkillers, opioids, ergotamine or triptans 10 or more days a month. […] Risk also rises if you use simple painkillers more than 15 days a month. […] Taking care of yourself can help prevent most headaches. […] Daily doses of caffeine also may add to medication overuse headaches.

• #42 Medication overuse headache: strategies for prevention and treatment using a multidisciplinary approach | HKMJ

  https://www.hkmj.org/abstracts/v24n6/617.htm

  Medication overuse headache, which affects patients who have migraines and frequent headaches, is prevalent worldwide and can severely impact daily functioning. […] Medication overuse headache is often not recognised by primary care physicians or general practitioners, as patients may overuse medications that are freely available without a prescription. […] Overuse of codeine-containing analgesics is particularly problematic and contributes to ongoing morbidity and opioid-related mortality. […] The estimated prevalence of medication overuse headache (MOH) in the general population ranges from 0.6% to 7%. […] A number of acute headache treatments may cause MOH, and the medications that are predominantly associated with MOH vary from country to country. […] Opioids such as codeine are particularly problematic, as they are consistently associated with increasingly severe headaches and poor outcomes after withdrawal.

• #43 Medication-overuse headache: a narrative review | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01755-w

  The current International Classification of Headache Disorders-3 (ICHD-3) includes MOH as a separate secondary disorder, described as headache occurring on 15 or more days/month for at least three months in a patient with a pre-existing headache disorder as a consequence of overuse of acute symptomatic medication. […] Indeed, a longitudinal study revealed that patients with episodic migraine were more likely to progress to chronic migraine if they were taking medication containing opioids or barbiturates, suggesting a medication-dependent effect. […] A study of Wilkinson and colleagues explored whether overuse of opiates (sic.) induces chronic daily headache in those with migraine who were post colectomy for ulcerative colitis for at least 1 year prior. […] The authors suggested that MOH may share some neurophysiological features with addiction.

• #44 Stopping the vicious cycle of rebound headaches – Harvard Health

  https://www.health.harvard.edu/blog/stopping-the-vicious-cycle-of-rebound-headaches-2019110718180

  A variety of medications can lead to rebound headaches. […] In fact, butalbital-containing medications and opioids have been shown to increase the risk of a persons migraine progressing from episodic (occurring zero to 14 days per month) to chronic (occurring 15 or more days per month). […] Medication overuse headaches usually stop when a person stops taking the headache medication. […] Some headache medications can be discontinued abruptly, while others may need to be tapered slowly. […] If you are taking opioids or butalbital-containing medications, talk to your doctor.

• #45 Medication overuse headache: strategies for prevention and treatment using a multidisciplinary approach | HKMJ

  https://www.hkmj.org/abstracts/v24n6/617.htm

  Medication overuse headache, which affects patients who have migraines and frequent headaches, is prevalent worldwide and can severely impact daily functioning. […] Medication overuse headache is often not recognised by primary care physicians or general practitioners, as patients may overuse medications that are freely available without a prescription. […] Overuse of codeine-containing analgesics is particularly problematic and contributes to ongoing morbidity and opioid-related mortality. […] The estimated prevalence of medication overuse headache (MOH) in the general population ranges from 0.6% to 7%. […] A number of acute headache treatments may cause MOH, and the medications that are predominantly associated with MOH vary from country to country. […] Opioids such as codeine are particularly problematic, as they are consistently associated with increasingly severe headaches and poor outcomes after withdrawal.

• #46 Medication overuse headache: strategies for prevention and treatment using a multidisciplinary approach | HKMJ

  https://www.hkmj.org/abstracts/v24n6/617.htm

  Medication overuse headache, which affects patients who have migraines and frequent headaches, is prevalent worldwide and can severely impact daily functioning. […] Medication overuse headache is often not recognised by primary care physicians or general practitioners, as patients may overuse medications that are freely available without a prescription. […] Overuse of codeine-containing analgesics is particularly problematic and contributes to ongoing morbidity and opioid-related mortality. […] The estimated prevalence of medication overuse headache (MOH) in the general population ranges from 0.6% to 7%. […] A number of acute headache treatments may cause MOH, and the medications that are predominantly associated with MOH vary from country to country. […] Opioids such as codeine are particularly problematic, as they are consistently associated with increasingly severe headaches and poor outcomes after withdrawal.

• #47 Thieme E-Journals – Seminars in Neurology / Abstract

  https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2006-939924

  There is considerable overlap in the mechanisms mediating migraine headache pain and sustained opioid-induced paradoxical pain. Both involve upregulation of calcitonin gene-related peptide and increased excitability of dorsal horn neurons. […] Dysfunction in the periaqueductal gray may explain why frequent analgesic use can result in medication overuse headache in migraineurs. […] Management of transformed migraine with medication overuse involves patient education, biobehavioral therapy, withdrawal of overused acute medications, bridge therapy for withdrawal headache, initiation of preventive medication, and close follow-up.

• #48 Medication overuse headaches – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/medication-overuse-headache/symptoms-causes/syc-20377083

  Your risk goes up if you use combined painkillers, opioids, ergotamine or triptans 10 or more days a month. […] Risk also rises if you use simple painkillers more than 15 days a month. […] Taking care of yourself can help prevent most headaches. […] Daily doses of caffeine also may add to medication overuse headaches.

• #49 Entstehung des Medikamenten-Übergebrauchs-Kopfschmerzes – Schmerzklinik Kiel

  https://schmerzklinik.de/en/development-of-medication-overuse-headache-muek/

  Es wird angenommen, dass diese Vernderung auf serotoninergen (5-HT) und mglicherweise endocannabinoid-vermittelten Mechanismen basiert. […] Die Erschpfung der zentralen schmerzmodulierenden Systeme als Folge des chronischen Medikamenten-bergebrauchs fhrt somit direkt zu einer graduell zunehmenden Sensitivierung der Schmerzwahrnehmung und bedingt kontinuierlich eine Hufigkeitssteigerung der Schmerzmitteleinnahme, die wiederum eine weitere Sensitivierung nach sich zieht. […] Diese pathophysiologischen Mechanismen machen verstndlich, warum vorbeugende Migrnemedikamente in ihrer Wirksamkeit aufgehoben werden, wenn gleichzeitig ein MK besteht. […] Fr die nachhaltige Therapie gibt es daher nur eine Lsung: Die stetige Medikamentenzufuhr muss gestoppt werden und eine Medikamentenpause oder bei Substanzen, die nicht weiter verwendet werden drfen, ein Medikamentenentzug eingehalten werden.

• #50 Entstehung des Medikamenten-Übergebrauchs-Kopfschmerzes – Schmerzklinik Kiel

  https://schmerzklinik.de/en/development-of-medication-overuse-headache-muek/

  Es wird angenommen, dass diese Vernderung auf serotoninergen (5-HT) und mglicherweise endocannabinoid-vermittelten Mechanismen basiert. […] Die Erschpfung der zentralen schmerzmodulierenden Systeme als Folge des chronischen Medikamenten-bergebrauchs fhrt somit direkt zu einer graduell zunehmenden Sensitivierung der Schmerzwahrnehmung und bedingt kontinuierlich eine Hufigkeitssteigerung der Schmerzmitteleinnahme, die wiederum eine weitere Sensitivierung nach sich zieht. […] Diese pathophysiologischen Mechanismen machen verstndlich, warum vorbeugende Migrnemedikamente in ihrer Wirksamkeit aufgehoben werden, wenn gleichzeitig ein MK besteht. […] Fr die nachhaltige Therapie gibt es daher nur eine Lsung: Die stetige Medikamentenzufuhr muss gestoppt werden und eine Medikamentenpause oder bei Substanzen, die nicht weiter verwendet werden drfen, ein Medikamentenentzug eingehalten werden.

• #51 Medication overuse headache – Australian Prescriber

  https://australianprescriber.tg.org.au/articles/medication-overuse-headache-1.html

  At least some of the characteristics of medication overuse headache may be understood by considering the mechanism of action. […] Triptan usage therefore results in tachyphylaxis (less effect for the same dosage) more quickly, at a lower frequency of use, and at a lower dosage than other non-narcotic analgesics. […] Receptor and enzyme downregulation in structures responsible for the transmission and reception of nociceptive input creates increased sensitivity to such input, resulting in a lowered threshold for pain perception. […] The essential treatment of medication overuse headache is withdrawal of the offending medication, but in most cases that is easier said than done. […] Following successful withdrawal of the overused medication, migraine prophylaxis, careful assessment of precipitants, counselling, a headache management plan and clear limits on the use of analgesia may all be required in order to prevent relapse. […] The prevalence of medication overuse headache is high and the condition is usually present for a long time before it is recognised and treated.

• #52 Medication Overuse Headache: Causes, Symptoms, and Treatments

  https://headacheaustralia.org.au/medication-overuse-headache/

  MOH can increase headache frequency and make the disease even less responsive to a management strategy, including some preventive treatments. […] Studies have shown that patients without migraine taking regular analgesics for non-headache related conditions like rheumatoid arthritis or osteoarthritis do not typically experience MOH. It seems as though you have to have migraine or tension headaches before you are at risk at developing MOH. […] We know that those with migraine are inherently sensitive within their sensory pathways to stimuli and analgesic medication can amplify this stimuli. This central sensitization pathway is something we know about, but there’s still a lot we don’t know. […] MRI studies have shown that when you take the offending drugs away, there is a reversible nature of this condition. MOH is reversible, it is curable in that sense. The underlying migraine condition is not necessarily curable at this stage, but this MOH component of it certainly is reversible with cessation or withdrawal of the drug.

• #53

• #54 Pathophysiology of Medication Overuse Headache: Current Status and Future Directions | SpringerLink

  https://link.springer.com/chapter/10.1007/978-3-319-15621-7_14

  Medication overuse headache (MOH) has been identified as a global epidemic in the management of headache. Frequent use, and overuse, of medications including triptans, opioids, ergot alkaloids, and drug combinations for treatment of primary headaches can promote the development of MOH in susceptible individuals. Similar underlying mechanisms might be associated with both migraine headache and MOH. Possible mechanisms that may be common to both migraine and MOH include an underlying state of central sensitization, along with alterations of descending pain modulatory circuits and biochemical changes that can promote pain amplification. […] Imaging studies and functional evaluation have suggested decreased efficiency of pain modulation, possibly reflecting diminished descending pain inhibition or increased pain facilitation or both, in both migraine and MOH patients. In preclinical studies, medications can induce a sensitized state where provocative challenge with putative migraine triggers can precipitate cutaneous allodynia and increased CGRP blood levels, consistent with human observations during migraine. Preclinical studies also demonstrate decreased thresholds for evoked cortical spreading depression following medication-induced sensitization that is accompanied by enhanced activation of the trigeminovascular system. Medications may therefore produce long-lasting alterations in central excitability that increase vulnerability to endogenous and exogenous mechanisms promoting migraine attack.

• #55 Frontiers | Medication overuse headache: a review of current evidence and management strategies

  https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1194134/full

  Medication overuse headache (MOH) is a common, challenging, and disabling condition that affects millions of people worldwide. MOH occurs when people who suffer from primary headaches, such as migraines or tension-type headaches, use painkillers too frequently or in excessive doses. This paradoxically leads to a worsening of headache frequency and severity. […] The precise pathophysiology of MOH remains uncertain. However, research shows that central sensitization has a major role. An expansion of the receptive nociceptive field, a decreased nociceptive threshold, and decreased noxious inhibitory control have been reported following chronic analgesic use. […] The frequent use of headache abortive medications is also thought to deplete 5-hydroxytryptamine (5-HT) in the central nervous system (CNS). This depletion leads to hyperexcitability in the cerebral cortex, potentially causing cortical spreading depression, as well as in the trigeminal system, which leads to increased sensitivity in both peripheral and central pain pathways. Reduced 5-HT levels also cause the trigeminal ganglia to release calcitonin gene-related peptide (CGRP), a peptide involved in pain transmission, which contributes to the sensitization of nociceptive trigeminal neurons.

• #56 Entstehung des Medikamenten-Übergebrauchs-Kopfschmerzes – Schmerzklinik Kiel

  https://schmerzklinik.de/en/development-of-medication-overuse-headache-muek/

  Es wird angenommen, dass diese Vernderung auf serotoninergen (5-HT) und mglicherweise endocannabinoid-vermittelten Mechanismen basiert. […] Die Erschpfung der zentralen schmerzmodulierenden Systeme als Folge des chronischen Medikamenten-bergebrauchs fhrt somit direkt zu einer graduell zunehmenden Sensitivierung der Schmerzwahrnehmung und bedingt kontinuierlich eine Hufigkeitssteigerung der Schmerzmitteleinnahme, die wiederum eine weitere Sensitivierung nach sich zieht. […] Diese pathophysiologischen Mechanismen machen verstndlich, warum vorbeugende Migrnemedikamente in ihrer Wirksamkeit aufgehoben werden, wenn gleichzeitig ein MK besteht. […] Fr die nachhaltige Therapie gibt es daher nur eine Lsung: Die stetige Medikamentenzufuhr muss gestoppt werden und eine Medikamentenpause oder bei Substanzen, die nicht weiter verwendet werden drfen, ein Medikamentenentzug eingehalten werden.

• #57 Can the Overuse of Medication Cause Chronic Migraine?

  https://www.healthline.com/health/migraine/medications-causing-headaches

  For some unknown reason, your body then turns on the medication. The more medication you take, the more headaches you get. The more headaches you get, the more medication you take. […] Before long, you can develop chronic migraine headaches because of your medication use. […] All of these medications can cause MOH if taken too frequently. […] The best way to treat chronic migraine caused by MOH is to stop taking the medication. […] Reducing your use of these medicines may be able to slow the progression of frequent headaches and prevent chronic migraine. […] Some doctors prefer to ease a patient’s transition from medication overuse by prescribing additional medications. These medicines are often designed to prevent migraine headaches and the need for pain-relieving medication. […] Medication-overuse headaches (MOH) may lead to chronic migraine. People who regularly take analgesics, ergots, triptans, or opioid medications are more at risk for MOH.

• #58

  https://bpac.org.nz/bpj/2008/september/overuse.aspx

  Medication-overuse headache is an increasingly common worldwide health problem. […] For most people with medication-overuse headache, there is no relief until all medication used for acute relief is withdrawn. […] The main way to prevent medication-overuse headache is to prevent medication overuse. […] Withdrawal symptoms which may be physical and psychological may last between two to ten days and include withdrawal headache (which initially may be worse than the medication-overuse headache), nausea, vomiting, hypotension, tachycardia, sleep disturbances and anxiety. […] Patient education is important to initiate withdrawal and to reduce the risk of relapse.

• #59 Addressing Medication Overuse Headache (MOH) in Clinical Practice – Association of Migraine Disorders

  https://www.migrainedisorders.org/medication-overuse-headache-in-clinical-practice/

  Medication overuse headache (MOH), formerly known as rebound headache, is a prevalent and disabling headache disorder commonly encountered in clinical practice. Globally, more than 60 million people are affected. Per the ICHD-3 criteria, MOH is defined as “headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped.” […] The Global Burden of Disease studies consistently rank medication overuse headache in the top 20 disorders causing years of life lost due to disability. […] Medication overuse headache occurs in up to 70% of people with chronic headache and may be a result of poorly treated pre-existing headache (ex. migraine or tension-type headache). It is one of the most important risk factors for headache chronification.

• #60 S5:Ep12 – Understanding Medication Overuse Headache (Rebound Headache) – Association of Migraine Disorders

  https://www.migrainedisorders.org/podcast/s5ep12-understanding-medication-overuse-headache-rebound-headaches/

  And finally, what happens is when the patients overuse these medications, the central sensitization or the activation of the neuronal networks or pain pathways is happening, and then the pain gets out of control, it becomes chronic. […] The prognosis of medication overuse is generally good, with 50% to 70% of patients demonstrating improvement after withdrawal therapy, especially in combination with prevention with medications. However, there may be some patients, like 10% to 40%, who may relapse within 5 years after withdrawal. […] Yes, if the person has a medication overuse and has episodic migraine, there’s high likelihood of developing chronic migraine. This has been shown in observational studies. And we know that from our clinical experience.

• #61 Medication-overuse headache: a narrative review | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01755-w

  The current International Classification of Headache Disorders-3 (ICHD-3) includes MOH as a separate secondary disorder, described as headache occurring on 15 or more days/month for at least three months in a patient with a pre-existing headache disorder as a consequence of overuse of acute symptomatic medication. […] Indeed, a longitudinal study revealed that patients with episodic migraine were more likely to progress to chronic migraine if they were taking medication containing opioids or barbiturates, suggesting a medication-dependent effect. […] A study of Wilkinson and colleagues explored whether overuse of opiates (sic.) induces chronic daily headache in those with migraine who were post colectomy for ulcerative colitis for at least 1 year prior. […] The authors suggested that MOH may share some neurophysiological features with addiction.

• #62 Pathophysiology of medication overuse headache: Insights and hypotheses from preclinical studies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5697138/

  As migraineurs are most susceptible to development of MOH, some common neural mechanisms between migraine and MOH might be expected. A review of migraine mechanisms and neuroplastic changes that occur with chronic medication exposure reveals considerable overlap between the two. […] Prolonged exposure to analgesics may lead to MOH through the up-regulation of neural regulators of vasodilation and neurogenic inflammation. […] Recent studies have begun to examine the effect of prolonged exposure to triptans in initiating peripheral neuroplasticity that may promote headache. […] Evidence from observational, prospective clinic-based, case-control, and population-based studies indicates that the frequent use of acute medications to treat migraine headache, in a substantial subgroup of individuals, leads to the progression of migraine from an episodic disorder to a syndrome of daily or near daily migraine. The risk of and time to progression, the phenotype of the daily headache, and the duration of withdrawal symptoms appears to vary based on the acute medication and its frequency of use. These features, together with the unique and selective vulnerability of migraine patients to this phenomena, highlights the possibility that the mechanism(s) by which acute medications lead to this progression may differ depending on the particular drug, and may be similar to the underlying biology of acute attacks of migraine. […] Preclinical studies have now provided evidence for several potential mechanisms for the development of MOH, including increases in evoked CSD, a possible role for neurogenic inflammation, peripheral and central sensitization, and descending facilitation.

• #63 Medication Overuse Headache | American Migraine Foundation

  https://americanmigrainefoundation.org/resource-library/medication-overuse-headache-3/

  During a migraine attack, popping a pill that cuts through the pain can feel like a lifesaver. But overusing medications can cause a new type of headache and reduce the effectiveness of treatment […] Medication overuse headache can be caused by prescription or over-the-counter medicines. It has three key effects: it makes migraine medication less effective over time; it causes dull, persistent head pain between migraine attacks; and it can cause the disease to progress, leading to more frequent migraine attacks in the long term. Those most at risk of developing medication overuse headache are people with migraine who have 10 or more headache days per month and treat each attack with medication […] Medication overuse headache can often cause migraine to irreversibly progress from episodic to chronic, so prevention is important. According to Friedman, there are warning signs people with migraine should watch for […] It’s important to tell your physician how often you take both over-the-counter and prescribed medications for your migraine. If you are worried that you’ve already been affected by medication overuse, ask your doctor to help you make a new treatment plan that will reduce your risk.

• #64 Medication overuse and migraine: Is there a connection?

  https://www.medicalnewstoday.com/articles/can-the-overuse-of-medication-cause-chronic-migraines

  Overusing some medications may trigger chronic migraine. Taking too much headache medication can also turn occasional migraine attacks into chronic migraine. Taking headache or migraine medication too frequently can lead to medication overuse headache (MOH). […] Experts do not yet fully understand how some headaches become chronic. However, research suggests overusing some medication increases the risk of episodic migraine becoming chronic. […] According to a 2021 review, 3 in 4 people with chronic migraine report overusing headache medication. […] In a 2019 review, researchers investigated data on migraine treatments and medication. They noted that medications containing opioids and barbiturates have a strong association with MOHs. […] Overusing pain relief medication can cause episodic migraine to turn into chronic migraine. Certain medications may be more likely to cause MOHs.

• #65 Medication overuse headache – The Migraine TrustVisualV1 – SearchVisualV1 – CrossVisualV1 – Home VisualV1 – CrossVisualV1 – Arrow

  https://migrainetrust.org/understand-migraine/types-of-migraine/medication-overuse-headache/

  The overuse of painkillers may also reduce the effectiveness of preventive migraine medications. […] The treatment is to stop the medicines that are being taken at a high level and to manage the underlying migraine attacks differently. […] If people have very frequent migraine attacks a preventive treatment is usually recommended. These can reduce the number of attacks, so that fewer painkillers are needed and reduce the likelihood of medication overuse headache.

• #66 Medication overuse headache from antimigraine therapy: clinical features, pathogenesis and management. – Document – Gale Academic OneFile

  https://go.gale.com/ps/i.do?id=GALE%7CA200669275&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=00126667&p=AONE&sw=w

  Medication overuse headache (MOH) is being recognised more often in headache, neurology and primary care clinics, but is still frequently overlooked. […] The most significant factor in the development of MOH is the lack of widespread awareness and understanding on the part of clinicians and patients. […] MOH should be viewed as an entity that is caused or propagated by frequently used medication taken for headache symptomatic relief. […] There are several different theories regarding the aetiology of MOH, including: (i) central sensitisation from repetitive activation of nociceptive pathways; (ii) a direct effect of the medication on the capacity of the brain to inhibit pain; (iii) a decrease in blood serotonin due to repetitive medication administration with attendant upregulation of serotonin receptors; (iv) cellular adaptation in the brain; and (v) changes in the periaqueductal grey matter. […] The principal approach to management of MOH is built around cessation of overused medication. […] Without discontinuation of the offending medication, improvement is almost impossible to attain. […] Prophylactic medications should be initiated for patients having 2 headache days per week.

• #67 Entstehung des Medikamenten-Übergebrauchs-Kopfschmerzes – Schmerzklinik Kiel

  https://schmerzklinik.de/en/development-of-medication-overuse-headache-muek/

  Es wird angenommen, dass diese Vernderung auf serotoninergen (5-HT) und mglicherweise endocannabinoid-vermittelten Mechanismen basiert. […] Die Erschpfung der zentralen schmerzmodulierenden Systeme als Folge des chronischen Medikamenten-bergebrauchs fhrt somit direkt zu einer graduell zunehmenden Sensitivierung der Schmerzwahrnehmung und bedingt kontinuierlich eine Hufigkeitssteigerung der Schmerzmitteleinnahme, die wiederum eine weitere Sensitivierung nach sich zieht. […] Diese pathophysiologischen Mechanismen machen verstndlich, warum vorbeugende Migrnemedikamente in ihrer Wirksamkeit aufgehoben werden, wenn gleichzeitig ein MK besteht. […] Fr die nachhaltige Therapie gibt es daher nur eine Lsung: Die stetige Medikamentenzufuhr muss gestoppt werden und eine Medikamentenpause oder bei Substanzen, die nicht weiter verwendet werden drfen, ein Medikamentenentzug eingehalten werden.

• #68 Headache from Medication Overuse | AMF

  https://americanmigrainefoundation.org/resource-library/medication-overuse/

  Medication-overuse headache (MOH) is a chronic daily headache and a secondary disorder in which acute medications used excessively causes headache in a headache-prone patient. […] MOH development is linked to baseline frequency of headache days per month, acute medication class ingested, frequency of acute medications ingested, and other risk factors. […] Medication overuse headache has been found to render headaches refractory to both pharmacological and non-pharmacological prophylactic medications, and also reduces the efficacy of acute abortive therapy for migraines. […] The most effective method to treat MOH is discontinuation of the medication that is overused and a combination of pharmacological, non-pharmacological, behavioral and physical therapy interventions. […] Medication-overuse headache is a secondary disorder caused by excessive use of acute medications.

• #69 Entstehung des Medikamenten-Übergebrauchs-Kopfschmerzes – Schmerzklinik Kiel

  https://schmerzklinik.de/en/development-of-medication-overuse-headache-muek/

  Solange der kontinuierliche bergebrauch weiter betrieben wird, kann kein Behandlungsverfahren eine entscheidende und nachhaltige Besserung erzielen. […] Fhrt die alleinige Information und Anleitung des Patienten nicht zur Beendigung des Medikamenten-bergebrauchs, ist eine Medikamentenpause oder eine Entzugsbehandlung erforderlich.

• #70 Entstehung des Medikamenten-Übergebrauchs-Kopfschmerzes – Schmerzklinik Kiel

  https://schmerzklinik.de/en/development-of-medication-overuse-headache-muek/

  Der bei weitem hufigste Grund fr eine Migrne, die an 15 oder mehr Tagen pro Monat auftritt bzw. fr ein Mischbild von Migrne und Kopfschmerzen vom Spannungstyp mit 15 oder mehr Kopfschmerztagen pro Monat, ist ein bergebrauch spezifischer Migrneakutmedikamente oder Schmerzmittel. […] Die allgemeinen Kriterien des Medikamenten-bergebrauch-Kopfschmerzes (MK) sind heute international in der internationalen Kopfschmerzklassifikation ICHD-3beta weltweit einheitlich definiert. […] Zerebrale bildgebende Studien haben strukturelle und funktionelle Vernderungen im Gehirn bei Patienten mit MK identifiziert. […] Die Hufigkeit der Medikamenteneinnahme pro Monat ist dabei ausschlaggebender signifikanter prognostischer Faktor fr die Entstehung und Aufrechterhaltung des MK. […] Weitere aktuelle Studien zur Entstehung des MK haben konsistent eine Sensitivierung und erhhte Erregbarkeit von trigeminalen und kortikalen Neuronen dokumentiert.

• #71 Medication-overuse headache: clinical profile and management strategies | Neurosciences Journal

  https://nsj.org.sa/content/28/1/13

  Increased gray matter volume mainly in the periaqueductal grey area, hippocampus, posterior cingulate cortex, thalamus, cerebellum, fusiform gyrus, and ventral striatum. […] The character of MOH is difficult to differentiate from other forms of chronic daily headache. […] An interaction between susceptible patient and a therapeutic medication used excessively is considered MOH.

• #72 Medication overuse headache – Wikipedia

  https://en.wikipedia.org/wiki/Medication_overuse_headache

  In some cases, individuals may be genetically predisposed to developing medication overuse headache. […] A PET study in patients with chronic analgesic overuse showed decreased activity in the orbitofrontal cortex of the brain, which is also seen in substance abuse. This suggests that there may be an underlying neurological susceptibility to addiction in some individuals. However, more research is needed to fully understand the complex interplay of factors that contribute to the development of MOH.

• #73 S5:Ep12 – Understanding Medication Overuse Headache (Rebound Headache) – Association of Migraine Disorders

  https://www.migrainedisorders.org/podcast/s5ep12-understanding-medication-overuse-headache-rebound-headaches/

  But the exact underlying mechanisms for medication-overuse headaches are not fully understood. But there are several hypotheses. It’s believed that medication overuse can affect the neural pathways involved in a primary headache disorder, particularly in those occurring with migraines. Genetic factors may play a role. Certain gene variations are associated with metabolic abnormalities. We call them like serotonergic, dopaminergic transmissions. They kind of involved in the processing of chemicals. And even pathways involved in drug dependence have been involved in this headache. […] We have also looked at neuroimaging studies, and these studies have shown that there are structural and functional, even metabolic changes in the brains of individuals with medication-overuse headaches. And specific areas, for example, of the brain, like we call them, they’re involved in the pain processing and also in emotional control of the pain, like hippocampus, periaqueductal gray, we call it thalamus, cerebellum, cingulate cortex. Those areas, interestingly, are showing alterations in patients with medication-overuse headache.

• #74 Medication overuse headache – Wikipedia

  https://en.wikipedia.org/wiki/Medication_overuse_headache

  In some cases, individuals may be genetically predisposed to developing medication overuse headache. […] A PET study in patients with chronic analgesic overuse showed decreased activity in the orbitofrontal cortex of the brain, which is also seen in substance abuse. This suggests that there may be an underlying neurological susceptibility to addiction in some individuals. However, more research is needed to fully understand the complex interplay of factors that contribute to the development of MOH.

• #75 Medication Overuse Headache: Causes, Symptoms, and Treatments

  https://headacheaustralia.org.au/medication-overuse-headache/

  MOH can increase headache frequency and make the disease even less responsive to a management strategy, including some preventive treatments. […] Studies have shown that patients without migraine taking regular analgesics for non-headache related conditions like rheumatoid arthritis or osteoarthritis do not typically experience MOH. It seems as though you have to have migraine or tension headaches before you are at risk at developing MOH. […] We know that those with migraine are inherently sensitive within their sensory pathways to stimuli and analgesic medication can amplify this stimuli. This central sensitization pathway is something we know about, but there’s still a lot we don’t know. […] MRI studies have shown that when you take the offending drugs away, there is a reversible nature of this condition. MOH is reversible, it is curable in that sense. The underlying migraine condition is not necessarily curable at this stage, but this MOH component of it certainly is reversible with cessation or withdrawal of the drug.

• #76 8.2 Medication-overuse headache (MOH) – ICHD-3

  https://ichd-3.org/8-headache-attributed-to-a-substance-or-its-withdrawal/8-2-medication-overuse-headache-moh/

  Headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped. […] 8.2 Medication-overuse headache is an interaction between a therapeutic agent used excessively and a susceptible patient. Among those with a previous primary headache diagnosis, most have 1. Migraine or 2. Tension-type headache (or both); only a small minority have other primary headache disorders such as 3.3 Chronic cluster headache or 4.10 New daily persistent headache. […] The diagnosis of 8.2 Medication-overuse headache is extremely important clinically. Epidemiological evidence from many countries indicates that more than half of people with headache on 15 or more days/month have 8.2 Medication-overuse headache. Clinical evidence shows that the majority of patients with this disorder improve after discontinuation of the overused medication, as does their responsiveness to preventative treatment. Simple advice on the causes and consequences of 8.2 Medication-overuse headache is an essential part of its management and can be provided with success in primary care. […] The behaviour of some patients with 8.2 Medication-overuse headache is similar to that seen with other drug addictions, and the Severity of Dependence Scale (SDS) score is a significant predictor of medication overuse among headache patients.

• #77 Medication-overuse headache: a widely recognized entity amidst ongoing debate | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0875-x

  Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. […] The underlying consensus for the entity of medication-overuse headache (MOH) consists of a deterioration of a pre-existing headache syndrome whilst overusing one or several types of acute painkilling treatments. […] Debates on the pathophysiological mechanisms, definitions of overuse and the nosology of MOH are ongoing. […] A complete understanding of the pathophysiology of MOH currently does not exist. […] Although the clinical aspects of MOH seem to be ambivalent, there is evidence for specific neurobiological aspects in MOH-models. […] Research shows that central sensitization has a major role in the pathophysiology of MOH. […] The serotonergic modulating system is presumably affected by chronic analgesic use, resulting in neuronal hyperexcitability, enhanced CSD and trigeminal nociception, caused by increased expression of pro-nociceptive serotonin 2A (5HT-2A) receptor binding sites and a decrease in the production of serotonin in the CNS.

• #78 Medication-overuse headache: a widely recognized entity amidst ongoing debate | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0875-x

  Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. […] The underlying consensus for the entity of medication-overuse headache (MOH) consists of a deterioration of a pre-existing headache syndrome whilst overusing one or several types of acute painkilling treatments. […] Debates on the pathophysiological mechanisms, definitions of overuse and the nosology of MOH are ongoing. […] A complete understanding of the pathophysiology of MOH currently does not exist. […] Although the clinical aspects of MOH seem to be ambivalent, there is evidence for specific neurobiological aspects in MOH-models. […] Research shows that central sensitization has a major role in the pathophysiology of MOH. […] The serotonergic modulating system is presumably affected by chronic analgesic use, resulting in neuronal hyperexcitability, enhanced CSD and trigeminal nociception, caused by increased expression of pro-nociceptive serotonin 2A (5HT-2A) receptor binding sites and a decrease in the production of serotonin in the CNS.

• #79

• #80 Medication-Overuse Headache: Update on Management

  https://www.mdpi.com/2075-1729/14/9/1146

  Increased central sensitization of trigeminal nociceptive pathways: Animal experiments provide evidence of structural and functional alterations following chronic analgesic use including the upregulation of neuropeptides involved in the transmission of pain (CGRP, substance P, and nitric oxide synthase) in trigeminal ganglia; the expansion of receptive fields, and the decreased nociceptive threshold of central trigeminal neurons. […] Increased peripheral trigeminal sensitization: Peripheral trigeminal sensitization of nociceptors in perivascular areas may play a role in MOH. […] Increased cortical excitability: Cortical excitability is associated with the cortical spreading depression (CSD) that accompanies migraine aura and leads to the increased sensitivity of the trigeminal pain pathway.

• #81 Medication-overuse headache: a widely recognized entity amidst ongoing debate | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-018-0875-x

  Medication overuse in primary headache disorders is a worldwide phenomenon and has a role in the chronification of headache disorders. […] The underlying consensus for the entity of medication-overuse headache (MOH) consists of a deterioration of a pre-existing headache syndrome whilst overusing one or several types of acute painkilling treatments. […] Debates on the pathophysiological mechanisms, definitions of overuse and the nosology of MOH are ongoing. […] A complete understanding of the pathophysiology of MOH currently does not exist. […] Although the clinical aspects of MOH seem to be ambivalent, there is evidence for specific neurobiological aspects in MOH-models. […] Research shows that central sensitization has a major role in the pathophysiology of MOH. […] The serotonergic modulating system is presumably affected by chronic analgesic use, resulting in neuronal hyperexcitability, enhanced CSD and trigeminal nociception, caused by increased expression of pro-nociceptive serotonin 2A (5HT-2A) receptor binding sites and a decrease in the production of serotonin in the CNS.

• #82 Medication-overuse headache: a narrative review | The Journal of Headache and Pain | Full Text

  https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-024-01755-w

  The mesocorticolimbic dopamine circuit, which is known to be altered in addiction, was studied in MOH patients by focusing on the ventromedial prefrontal cortex and substantia nigra/ ventral tegmental area complex, showing a dysfunction compared to controls and chronic migraine patients without medication overuse. […] The development of gepants, CGRP receptor antagonists, for the preventive treatment of migraine offers an important advance since if these medicines, useful also for acute treatment do not cause MOH, this would be a crucial advance.

• #83 A Descriptive Review of Medication-Overuse Headache: From Pathophysiology to the Comorbidities

  https://www.mdpi.com/2076-3425/13/10/1408

  Medication-overuse headache (MOH) is a secondary headache that is classified by the third edition of the International Classification of Headache Disorders as a group of headaches attributable to the administration or discontinuation of various substances. MOH occurs more than 15 days per month in patients with preexisting headaches. It occurs as a result of regular (at least 3 consecutive months) overuse (10 or 15 days, depending on the type of medication) of drugs used as acute or symptomatic headache therapy. […] The pathophysiology of medication-overuse headaches (MOHs) is not fully understood. In addition to factors related to previous headaches, psychological factors, personality traits, and a genetic predisposition play important roles. Genes involved in complex processes of endogenous pain modulation, drug metabolism, and the serotonin and dopamine systems have been linked to the development of MOH. Excessive use of analgesics leads to facilitation of supraspinal pain transmission.

• #84 Frontiers | Medication overuse headache: a review of current evidence and management strategies

  https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2023.1194134/full

  MOH is linked to biochemical, structural, and functional changes in the brain. Among patients with MOH, psychiatric comorbidities are very prevalent. This association could be indicative of a potential causal role. Examples include abnormal personality traits, especially neuroticism, as well as OCD, depression, anxiety, and sleep disorders like insomnia. […] The primary treatment for a drug overuse headache is medication withdrawal. Simple counseling is sometimes all that is necessary to manage MOH. Rescue and bridging medicines are useful depending on the severity of withdrawal symptoms; nevertheless, reuse of overused medication should be avoided. […] MOH prevention requires prophylaxis and lifestyle adjustments, with topiramate being the sole drug with moderate evidence for preventive therapy. MOH is a preventable and treatable condition that requires awareness, education, and cooperation between patients and health professionals.

• #85 Addressing Medication Overuse Headache (MOH) in Clinical Practice – Association of Migraine Disorders

  https://www.migrainedisorders.org/medication-overuse-headache-in-clinical-practice/

  Medication overuse headache is characterized by: […] – Escalating frequency of headache attacks […] – Progressive use of acute therapies resulting in chronic headache intractable to treatment […] Medication overuse headache is a significant risk factor for the chronification of migraine. […] Recognizing risk factors for migraine progression will allow clinicians to suggest protective interventions against migraine progression and decrease the likelihood of medication overuse headache. […] Identifying and appropriately treating MOH would help patients receive therapies they need. […] However, the authors recommend the use of preventive medication at the time of withdrawal to treat medication overuse headache. When preventive therapy was initiated at the time of withdrawal, 74.2% of patients reverted to episodic migraine and 96.8% of patients had no evidence of MOH. […] Encouraging clinicians to create a culture of prevention is a crucial step in reducing the burden of medication overuse headache.

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