Symptomatic Medication Overuse Research Articles

Reversion of chronic to episodic migraine in working age and botulinum toxin-resistant patients treated with fremanezumab: A real-life study.

The objectives of this real-life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non-steroidal anti-inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre-treatment in MHDs (28.0vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non-converters than in converters, as was the percentage of patients with anxiety. High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion.

Medication-overuse headache-a review of different treatment strategies.

Medication-overuse headache (MOH) can develop from primary headaches. MOH is usually the result of overuse of symptomatic medications. It is a noteworthy personal and societal burden. The identification and treatment of patients at risk for MOH is an essential component of MOH management. Medication overuse can be modifiable and can advance from episodic to chronic migraine. Treatment for MOH is complex, and experts in the field have varied views on the most appropriate strategy for MOH treatment. The objective of this review is to give a comprehensive synopsis of the literature for the management of MOH. Treatment strategies, such as detoxification and prevention, are the debatable issues. Medication withdrawal is the foundation for management. The available literature suggested abrupt withdrawal with preventive approaches for early management. Bridging therapy could be useful to get relief from withdrawal symptoms. Multidisciplinary choices proved beneficial in supporting withdrawal and preventing relapse. Worldwide, the termination of overused medications has been observed as a standard treatment strategy; however, patient-specific approaches should be taken.

Medication Overuse Headache, Chronic Migraine and Monoclonal Antibodies Anti-CGRP: A Real-World Study.

Medication overuse headache (MOH) in chronic migraineurs may be a cause or consequence of the overuse of symptomatic medications for headache attacks. It is highly prevalent in tertiary centers. We compared the efficacy of 3 anti-CGRP monoclonal antibodies with traditional pharmacological agents in patients with chronic migraine (CM) and MOH. A randomized, cross-sectional, prospective, and open trial with real-world comparison groups was carried out. The sample consisted of 100 consecutive patients having CM and MOH. Eighty-eight patients (65 women and 23 men) were included in the study and divided into 4 groups: those having used erenumab (19.3%), galcanezumab (29.6%), fremanezumab (25%) and conventional medications, and the control group (26.1%). Ages ranged from 18 to 78 years (mean, 44.1 ± 13.6 years). In the 6 months of follow-up, there was a significant reduction in the number of headache days in the 3 groups when compared with the control (P < 0.0001). The small number of patients included in each group and the open design do not allow definitive conclusions, but the use of anti-CGRP monoclonal antibodies in patients with CM and MOH may result in lessening the number of headache days when compared with conventional treatment with drugs.

Monoclonal antibodies for chronic migraine and medication overuse headache: A real-world study.

Medication-overuse headache is highly prevalent in tertiary care centers. It may be a cause or consequence of the overuse of symptomatic medications for migraine attacks. We aimed to compare the efficacy of anti-CGRP monoclonal antibodies (mAbs) added to conventional pharmacological treatments in patients with chronic migraine (CM) and medication overuse headache (MOH). A cross-sectional, prospective, randomized, open study with real-world comparison groups of patients was carried out. The sample consisted of 200 patients with CM and MOH, who received the same approach to withdraw overused medications, started preventative treatment, and either did or did not receive mAbs. A total of 172 patients (126 women and 46 men) were included in the study and divided into two groups: group one consisting of 58 patients (control) and group two of 114 patients who used mAbs added to conventional pharmacological agents. The mean age was 44.1 ± 13.6 years, ranging from 18 to 78 years. In the 3 months follow-up after starting the treatment, both groups presented headache frequency reduction, but those with monoclonal antibodies had a significantly higher reduction in the number of headache days and symptomatic medication intake when compared to the control (p < 0.0001). The addition of an anti-CGRP monoclonal antibody to the treatment for medication overuse headaches in chronic migraineurs may result in decreasing headache frequency and symptomatic medication use when compared to conventional treatments with drugs.

Medication overuse headache: Updating of the French recommendations regarding the treatment strategies.

Regular and frequent use of analgesics and acute antimigraine drugs can increase the frequency of headache, and induce the transition from episodic to chronic migraine or medication-overuse headache (MOH). The one-year prevalence of this condition is between 1% and 2% in Europe, provoking substantial burden. MOH is more prevalent in people with comorbid depression, anxiety, and other chronic pain conditions. This paper aims at presenting an updating of French recommendations regarding treatments strategies. Prior French recommendations, published in 2014, were written in French. A literature search in the major medical databases including the terms "medication overuse headache", "symptomatic medication overuse", published between 2010 and 2020 was carried out. Three main strategies can be recommended and conducted in parallel: education and explanations about the negative consequences of overusing acute antimigraine drugs, discontinuation of the overused medication, and finally, preventive drug therapy and non-pharmacological prevention. Medication overuse headache remains a debated problem and evidence for the most effective treatment strategy is needed.

Chronic Migraine with Medication Overuse: Clinical Pattern and Evolution from a Retrospective Cohort in Seville, Spain

Chronic migraine (CM) with medication overuse (MO) develops in patients with a pre-existing primary headache after a regular overuse of symptomatic medication. In these patients, headache crisis may occur together with other painful pathologies which can increase the frequency and intensity of the pain episodes. Such comorbidities need to be assessed as they influence the clinical evolution of the patients. A cohort of 102 patients (89 women and 13 men) with a diagnosis of chronic migraine (CM) with medication overuse (MO) was retrospectively analysed. Patients enrolled in the study were actively followed up 23 months in the Neurology Service of the University Hospital Virgen del Rocio in Seville, Spain. We observed that most of the patients overused multiple symptomatic drugs (34.3%) and NSAIDs (26.5%). In this cohort, the most effective treatments were topiramate and the combination of multiple prophylactic drugs with an effectiveness of 41.6% and 53.8%, respectively, at the end of the study. We observed the ratio of patients reducing their headache crisis was significantly higher among patients abandoning their medication overuse. Detoxification, or withdrawal of medication overuse, is linked to the reduction of the frequency and intensity of 50% or more of the headache crisis in these patients.

Trigeminal ganglion transcriptome analysis in 2 rat models of medication-overuse headache reveals coherent and widespread induction of pronociceptive gene expression patterns.

We attempted to gather information on the pathogenesis of medication-overuse headache, as well as on the neurochemical mechanisms through which symptomatic medication overuse concurs to headache chronification. Transcriptional profiles were therefore evaluated as an index of the homeostasis of the trigeminovascular system in the trigeminal ganglion of female rats exposed for 1 month to daily oral doses of eletriptan or indomethacin. We report that both drug treatments change trigeminal ganglion gene expression to a similar extend. Of note, qualitative transcriptomic analysis shows that eletriptan and indomethacin prompt nearly identical, increased expression of genes coding for proteins involved in migraine pathogenesis and central pain sensitization such as neuropeptides, their cognate receptors, prostanoid, and nitric oxide-synthesizing enzymes, as well as TRP channels. These genes, however, were not affected in thoracic dorsal root ganglia. Of note, lowering of orofacial nociceptive thresholds, as well as forepaw hyperalgesia occurred in both indomethacin- and eletriptan-treated rats. Our study reveals that chronic rat exposure to 2 acute headache medications with completely different mechanisms of action prompts pain sensitization with highly similar induction of pronociceptive genes selectively within the trigeminal ganglion. Data further our understanding of medication-overuse headache pathogenesis and provide hints for specific mechanism-based treatment options.

Neurobiology of chronicization.

In the past few years, research on chronicization of headache has focussed primarily on migraine, even though there are other types of primary headache that over time can turn into chronic forms. Only a minority of migraine sufferers will develop a chronic condition, with attacks that are likely to vary in their clinical features. As a result, in chronic migraine the specific diagnostic criteria for this headache type do not always exhibit the typical features of migraine. Among the factors that play a major role in favouring chronicization are a high frequency of migraine attacks since the beginning, overuse of symptomatic medication and onset of depression or arterial hypertension. Several neurophysiology, biochemistry and functional neuroimaging studies suggest that chronic migraine may be associated with structural, functional and metabolic changes in the brain, especially involving the brainstem.

Your Loved One Has Migraines.

Your Loved One Has Migraines.

The use of onabotulinum toxin A (Botox(®)) in the treatment of chronic migraine at the Parma Headache Centre: a prospective observational study.

Chronic migraine is a debilitating headache, whose treatment is often complicated by the concomitant overuse of symptomatic medication and by the poor efficacy of standard prophylactic treatments. The PREEMPT studies have demonstrated the efficacy and tolerability of onabotulinum toxin A (Botox(®)) in the treatment of this headache type. Data about its use in clinical practice are still scarce. Our study evaluated all subjects with chronic migraine who were treated with onabotulinum toxin A between February 2014 and November 2015 at the Parma Headache Centre. Botox was injected according to the PREEMPT paradigm every 3months. The data about variations in the number of headache days and in symptomatic medication intake before and after the Botox injections were collected from the patients' headache diaries. The study also evaluated tolerability to treatment, disability, and depressive symptoms. Of the 52 treated subjects, 14 received Botox treatment for at least 9months and showed a significant decrease in the median number of headache days (from 19 to 14.5, p=0.011) and in the median number of days of symptomatic medications intake and symptomatic drugs. Overall, the treatment was well tolerated. The average MIDAS and BDI-II scores after 9months were reduced, though not significantly. The treatment with Botox proved effective and well tolerated in our clinical practice. Further studies on larger patient samples will help shed light on the persistence of the drug's effect at long term and identify the predictive factors of response to treatment.

P010. OnabotulinumtoxinA for treatment of chronic migraine: results after 1 year of treatment.

OnabotulinumtoxinA (OnabotA) was approved for treatment of chronic migraine (CM) following the PREEMPT trials[1, 2], and was licensed in Italy in February 2013. Thus, in December 2013 we began to offer OnabotA to patients with CM who did not respond to other preventive therapy (mostly topiramate, beta blockers, amitriptyline and calcium channel antagonists). Demographic and migraine characteristics of patients were recorded, and changes in monthly migraine days and headache intensity (the latter variable was evaluated only after the first session of treatment), as well as, the number of symptomatic medications intake, were assessed. From December 2013, 40 patients (9 males, 31 females) were treated with at least four therapeutic sessions. Their mean age (± SD) at treatment onset was 51.3±12.6 years (range: 27-80). All the patients fulfilled the ICHD-III criteria for CM[3] and 28 (70%) were receiving other preventive therapy. In 34 of these patients (85%) overuse of symptomatic medications was observed at the onset of treatment. After obtaining an informed consent, we administered OnabotA according to the PREEMPT protocol (155 UI for a total of 31 injections divided across 7 head/neck muscles), performing no additional injections in the first session (from the second session we also adopted “follow the pain” protocol), and we gave the patients a paper diary to register the headache evolution. After one year of treatment we analyzed the data related to the 40 patients, observing positive results in all the variables considered. In particular, following 1-year treatment there was a reduction from 25.1±6.1 to 19.8±9.1 in the mean (± SD) number of monthly migraine days (reduction of 21%, p < 0.0001). The intake of symptomatic medications was reduced of about 12%, but the difference was not statistically significant. Most (78%) of the patients (n = 23) who had accurately registered the data reported that the greatest clinical benefit of OnabotA was the reduction in the headache intensity. Finally, no severe adverse event was observed, and mild pain in the injection site was the most reported experience. No patient discontinued the treatment because of side effects. We can conclude that the use of OnabotA according to the PREEMPT paradigm is an effective and well-tolerated treatment in patients with chronic migraine in a real-life setting. Written informed consent to publication was obtained from the patient(s).

O041. GRIA3 (glutamate receptor, ionotropic, ampa 3) gene polymorphism influences cortical response to somatosensory stimulation in medication-overuse headache (MOH) patients

Medication-overuse headache (MOH) is a secondary form of chronic headache developed by migraineurs after prolonged symptomatic medication overuse. Bio-behavioural sensitization is a key mechanism in MOH pathophysiology, as evidenced by cortical somatosensory evoked potentials (SSEPs) studies. While episodic migraineurs, recorded between attacks, showed lower initial SSEP amplitudes and lack of habitation during stimulus repetition, in MOH patients the SSEPs were initially higher and further increased during stimulus repetition, resulting in a persistent sensitisation proportional to the duration of the headache chronification phase. The central sensitization seems to be strongly dependent by glutamate. Amongst various gene polymorphisms in the glutamatergic system, only the Glutamate Receptor Ionotropic AMPA 3 (GRIA3) was previously associated with migraine. The aim of our study was to verify whether GRIA3 rs3761555 single nucleotide polymorphism (SNP) could influence processes of central sensitization of MOH patients.

Dependency-like behaviors and pain coping styles in subjects with chronic migraine and medication overuse: results from a 1-year follow-up study.

BackgroundEven after successful detoxification, 20-40% of subjects presenting chronic migraine with symptomatic medication overuse (CMwMO) relapse into medication overuse within one year. In this restrospective analysis on subjects referred to our center for detoxification, we investigated whether personality traits, dependency-like behaviors and pain coping styles predicted those who relapsed into medication overuse within the 12 months following the detoxification and those who did not.Methods63 patients with CMwMO were assessed for personality traits, mood and anxiety, pain coping styles and dependency-like behaviors prior-to and one year after a detoxification program.ResultsOf the 42 subjects who attended 1-year follow-up interviews, 11 relapsed into medication overuse despite a temporary benefit from detoxification and did not show clinical or psychological improvement, instead reporting increased anxiety and unmodified perpetuation of severe dependency-like behaviors. In contrast, subjects who did not relapse into medication overuse had clinical improvements that generalized to untreated domains, including decreased depressive symptoms and dependency-like behaviors, although showing unmodified low internal control over pain.ConclusionsSubjects who did not fall into medication overuse throughout the 12 months following the detoxification showed improved clinical, affective and dependence-related outcomes, but not pain coping strategies. Conversely, subjects who relapsed within one year into CMwMO continued to experience significant disability, pain intensity, and dependency-like behaviors. We believe that the persistence of maladaptive pain coping strategies and residual symptomatology increase the risk for recurrent relapses, against which pharmacological interventions are only partially effective. Further studies investigating predictors of relapse are needed to inform multi-disciplinary interventions for CMwMO.

Headache in the elderly: a series of 262 patients

IntroductionAlthough headache prevalence decreases in patients older than 65, headaches are a common complaint and their different clinical and therapeutic features must be understood. This article analyses the clinical characteristics of elderly patients treated in an outpatient headache unit. MethodsWe collected demographic and clinical data from patients treated in a tertiary hospital headache unit between January 2008 and May 2013. Headaches were codified according to the International Classification of Headache Disorders, 2nd edition (ICHD-2). ResultsOf a total of 1868 patients treated, 262 patients (14%, 189 women and 73 men) were older than 65 years. Ninety-nine (68 women, 31 men, 5.3% of the total) were over 75. Headaches began after the age of 65 in only 136 patients (51.9%). The 362 headaches were codified as follows: 23.8% as Group 1 (migraine) and 28.7% as Group 2 (tension-type headache). We diagnosed 58 (16%) secondary headaches; 26 (7.2%) were classified as Group 13 (cranial neuralgias) and 23 (6.4%) in Group 14 (other headaches). Symptomatic medication overuse was detected in 38 patients (14.5%). We also identified headaches considered typical in the elderly, including chronic migraine (41 cases), hypnic headache (6), occipital neuralgia (4), SUNCT (2), cervicogenic headache (1), primary cough headache (1), and giant cell arteritis (2). ConclusionsElderly patients were frequently treated in our outpatient headache unit. Tension-type headache was the most common diagnosis in this population. Geriatric headache syndromes such as hypnic headache or occipital neuralgia were also represented in our series.

Cefaleas en la persona mayor: características de una serie de 262 pacientes

IntroductionAlthough headache prevalence decreases in patients older than 65, headaches are a common complaint and their different clinical and therapeutic features must be understood. This article analyses the clinical characteristics of elderly patients treated in an outpatient headache unit. MethodsWe collected demographic and clinical data from patients treated in a tertiary hospital headache unit between January 2008 and May 2013. Headaches were codified according to the International Classification of Headache Disorders, 2nd edition (ICHD-2). ResultsOf a total of 1868 patients treated, 262 patients (14%, 189 women and 73 men) were older than 65 years. Ninety-nine (68 women, 31 men, 5.3% of the total) were over 75. Headaches began after the age of 65 in only 136 patients (51.9%). The 362 headaches were codified as follows: 23.8% as Group 1 (Migraine) and 28.7% as Group 2 (Tension-type headache). We diagnosed 58 (16%) secondary headaches; 26 (7.2%) were classified as Group 13 (Cranial neuralgias) and 23 (6.4%) in Group 14 (Other headaches). Symptomatic medication overuse was detected in 38 patients (14.5%). We also identified headaches considered typical in the elderly, including chronic migraine (41 cases), hypnic headache (6), occipital neuralgia (4), SUNCT (2), cervicogenic headache (1), primary cough headache (1), and giant cell arteritis (2). ConclusionsElderly patients were frequently treated in our outpatient headache unit. Tension-type headache was the most common diagnosis in this population. Geriatric headache syndromes such as hypnic headache or occipital neuralgia were also represented in our series.

Obsessive–compulsive aspects as predictors of poor response to treatments in patients with chronic migraine and medication overuse

Patients with chronic migraine (CM) and medication overuse (MO) have a high frequency of psychiatric comorbidity or psychopathological traits, the presence of which may have important implications for the course of the CM and the MO, both for response to treatment and possible relapses. Overuse of symptomatic drugs is regarded as one of the most important risk factor for the transformation of episodic migraine into CM and drug-seeking tendency due to fear of headache in chronic migraine patients shares with obsessive-compulsive disorder (OCD) the compulsive quality of the behavior. Aim of this study was to review the clinical history of a sample of CM patients with MO in which an obsessive-compulsive trait was identified, performing a comparison with a sample of patients without obsessive-compulsive trait. We selected 14 patients with positivity to Spectrum Project OBS (obsessive-compulsive disorder) questionnaire and other 14 patients with negativity to the same tool from among a sample of patients who were enrolled in a previous study on the psychopathological profile of patients suffering from CM with MO. According to data obtained from the clinical records referring to the previous 5 years, patients with OBS questionnaire positivity showed a worse clinical course and a tendency to early relapse in MO after symptomatic medication withdrawal. Our results show that the comorbidity of OCD should be always evaluated in patients with CM and MO as it may play a relevant role--particularly if not treated--among the risk factors favoring the progression of episodic migraine to the chronic form, and/or the tendency to a pathological behavior that prompts the overuse of symptomatic medications.

Epidemiological classification and social impact of chronic headache

The current prevalent opinion is that a diagnosis of chronic headache should be established in patients who have had a form of primary headache other than cluster headache on at least 15 days a month for at least 3 months. Chronic headache so defined includes four different subtypes: hemicrania continua and new daily persistent headache--two rare forms currently included in the group "Other primary headaches" of the 2004 International Classification of Headache Disorders, second edition (ICHD-II)--chronic tension-type headache, and chronic migraine. Regarding the latter, which has been better known lately as transformed migraine, the current revised diagnostic criteria establish that migraine must be present on at least 8 of the at least 15 days of headache per month and that there must not be any overuse of symptomatic medication. Chronic headache affects about 3-5% of the general population and results in a variety of negative repercussions both on individuals and on society at large.

Chronic Migraine With Medication Overuse Pre–Post Withdrawal of Symptomatic Medication: Clinical Results and fMRI Correlations

Chronic migraine with symptomatic medication overuse (CMwMO) is a common and often debilitating clinical condition. Withdrawal of the offending drug(s) is considered the first step in management. Functional magnetic resonance imaging (fMRI) may be a useful technique for obtaining information on particular neuronal changes in the pain network involved in this condition. To identify specific fMRI patterns in patients suffering from CMwMO before and after withdrawal intervention. We collected fMRI data from a group of patients suffering from CMwMO, evaluating those patients prior to and 6 months following withdrawal. We applied stimuli at sites far removed from where the headaches were experienced. Moreover, pre-intervention fMRI data from the headache patients were compared with those obtained from headache-free and otherwise healthy controls. Before withdrawal, the right supramarginal gyrus, the right inferior and superior parietal cortex were hypoactive. Activity recovered to almost normal 6 months after withdrawal of the offending medications. The hypoactivation we detected in the lateral pain system indicate that there exists a modification of the pain network in CMwMO and that these changes are reversible with therapy.

Proposal for a new classification of chronic headache

Since the publication of the second edition of the International Classification of Headache Disorders (ICHD-2) in 2004, a fiery debate has been raging about chronic daily headache in general and about chronic migraine and medication overuse headache in particular. Based on a number of considerations and observations on the current state of knowledge, a proposal is advanced that suggests a few changes to ICHD-2, namely: (1) differentiation of migraine without aura at the second-digit level into infrequent, frequent and very frequent, based on frequency of attacks. (2) Inclusion of transformed migraine among the complications of migraine; this entry should be coded to 1.5.1 replacing chronic migraine and the only diagnostic criterion that needs to be changed over those already listed in the revised ICHD-2 (ICHD-2R) is its temporal pattern (more than 20 days/month for 1 year or more and never with more than 5 headache-free consecutive days). (3) Differentiation of transformed migraine at the fourth-digit level depending on the presence or absence of symptomatic medication overuse (i.e. use for more than 20 days/month) regardless of whether overuse played any role in the worsening of the headache. (4) Switching of medication overuse headache to the Appendix with other diagnostic criteria to be defined.

Occipital Nerve Blocks: Effect of Symptomatic Medication

To explore the effect of symptomatic medication overuse (SMO) and headache type on occipital nerve block (ONB) efficacy. We conducted a chart review of all of the ONBs performed in our clinic over a 2-year period. Of 108 ONBs with follow-up data, ONB failed in 22% of injections overall. Of the other 78%, the mean decrease in head pain was 83%, and the benefit lasted a mean of 6.6 weeks. Failure rate without SMO was 16% overall, and with SMO was 44% overall (P < .000). In those who did respond, overall magnitude and duration of response did not differ between those with and those without SMO. Without SMO, ONB failure rate was 0% for postconcussive syndrome, 14% for occipital neuralgia, 11% for non-intractable migraine, and 39% for intractable migraine. With SMO, failure rate increased by 24% (P = .14) in occipital neuralgia, by 36% (P = .08) for all migraine, and by 52% (P = .04) for non-intractable migraine. SMO tripled the risk of ONB failure, possibly because medication overuse headache does not respond to ONB. SMO increased ONB failure rate more in migraineurs than in those with occipital neuralgia, possibly because migraineurs are particularly susceptible to medication overuse headache. This effect was much more pronounced in non-intractable migraineurs than in intractable migraineurs.