Update on the Pharmacological Treatment of Chronic Migraine.

Chronic migraine (CM) is a common and disabling disorder that remains underdiagnosed and poorly treated. Significant unmet therapeutic needs add to the burden of this disorder; even when CM is recognized, effective treatment options are limited and randomized controlled trials supporting the use of various preventive medications are sparse. In this review, we discuss the available options for CM treatment. Currently the only FDA-approved treatment for CM prevention is onabotulinumtoxinA. Two double-blind studies have demonstrated the efficacy of topiramate for CM prevention, but it is not FDA-approved for this indication. Treatments in development for migraine will also be reviewed. Advancements in the understanding of migraine pathogenesis have identified new targets for both acute and preventive treatment and have engendered the development of targeted and mechanism-based therapies. The need for more effective treatment for CM patients, which has long since been identified, is now being addressed. Several of the emerging treatments for migraine prevention are under investigation specifically for CM or high-frequency episodic migraine.

Risk of medication overuse headache across classes of treatments for acute migraine.

BACKGROUND: The most commonly prescribed medications used to treat migraine acutely are single analgesics, ergots, opioids, and triptans. Due to varying mechanisms of action across drug classes, there is reason to believe that some classes may be less likely than others to elicit Medication Overuse Headache (MOH) than others. We therefore aimed to determine whether certain classes of acute migraine drugs are more likely to elicit MOH than others. METHODS: A comprehensive systematic literature was conducted to identify studies of varying designs that reported on MOH within the considered treatment classes. Only studies that reported MOH according to the International Classification of Headache Disorders (ICHD) were considered. Since no causal comparative design studies were identified; data from prevalence studies and surveys were retrieved. Prevalence-based relative risks between treatment classes were calculated by integrating both medication overuse and medication use from published studies. For each pair wise comparison, pooled relative risks were calculated as the inverse variance weighted average. RESULTS: A total of 29 studies informed the relative risk between treatment classes, all of which reported country-specific data. Five studies reported country-specific medication use data. For triptans versus analgesics the study relative risks generally favored triptans. The pooled relative risk was 0.65 (i.e., relative risk reduction of 35 %). For ergots versus analgesics, a similar trend was observed in favor of ergots with a relative risk of 0.41. For triptans versus ergots, the direction of effect was mixed, and the pooled relative risk was 1.07. Both triptans and ergots appeared favorable when compared to opioids, with pooled relative risks of 0.35 and 0.76, respectively. However, the evidence was limited for these comparisons. Analgesics and opioids also appeared to yield similar risk of MOH (pooled relative risk 1.09). CONCLUSION: Our study suggests that in patients receiving acute migraine treatment, analgesics and opioids are associated with a higher risk of developing MOH compared with other treatments. These findings provide incentive for better monitoring of use of analgesics and opioids for treating acute migraine, and suggest possible clinical preference for use of so-called "migraine-specific" treatments, that is, triptans and ergots.

Assessing and managing medication overuse headache in Australian clinical practice.

More than 3 million Australians are estimated to have migraine disorders, and over a quarter of a million Australians are estimated to have medication overuse headache (MOH). The personal, societal and economic burden of MOH is high. MOH impacts an individual's ability to work or study, care for family or themselves, culminating in poor quality of life. Accurate and timely diagnosis and treatment of MOH are imperative. Withdrawal failures and relapse rates are high in MOH. Treatment of MOH is aimed at ceasing medication overuse and reducing monthly migraine days with the aim of achieving a pattern of well-controlled episodic migraine. Current treatment approaches in routine practice include withdrawal with preventive treatment, withdrawal with optional preventive treatment in the subsequent weeks and preventive treatment without withdrawal. This viewpoint article provides an overview of managing MOH in Australian clinical practice, with a focus on the importance of patient education and the role of preventive treatment in supporting patients as they withdraw from acute migraine medication(s).

Complementary and alternative approaches to the treatment of tension-type headache.

While pharmacotherapy with nonsteroidal anti-inflammatories (NSAIDs) and tricyclic antidepressants comprises the traditional treatment of tension-type headaches (TTH), the use of other therapeutic approaches in combination with medications can increase the success of treatment. Patients with comorbid mood disorders and frequent headaches may particularly benefit from some nonpharmacologic approaches. This review focuses on complementary and alternative approaches to tension-type headache treatment, including psychological therapies, acupuncture, and physical treatments. The current evidence indicates that EMG biofeedback (BFB) is effective in the treatment of TTH, and cognitive behavioral therapy and relaxation training may also be beneficial. Physical therapy and acupuncture may be considered in patients with frequent TTH, but the scientific basis is limited.

Alternative headache treatments: nutraceuticals, behavioral and physical treatments.

There is a growing body of evidence supporting the efficacy of various complementary and alternative medicine approaches in the management of headache disorders. These treatment modalities include nutraceutical, physical and behavioral therapies. Nutraceutical options comprise vitamins and supplements (magnesium, riboflavin, coenzyme Q(10), and alpha lipoic acid) and herbal preparations (feverfew, and butterbur). Although controversial, there are some reports demonstrating the benefit of recreational drugs such as marijuana, lysergic acid diethylamide and psilocybin in headache treatment. Behavioral treatments generally refer to cognitive behavioral therapy and biobehavioral training (biofeedback, relaxation training). Physical treatments in headache management are not as well defined but usually include acupuncture, oxygen therapy, transcutaneous electrical nerve stimulation, occlusal adjustment, cervical manipulation, physical therapy, massage, chiropractic therapy, and osteopathic manipulation. In this review, the available evidence for all these treatments will be discussed.

The Evolution of Medication Overuse Headache: History, Pathophysiology and Clinical Update.

Medication overuse headache (MOH), the development or worsening of chronic headache resulting from frequent and excessive intake of medications used for acute treatment of headache, is a common secondary headache disorder and is associated with significant personal and societal burdens. The plausible physiologic mechanism is that chronic exposure to acute care migraine treatment leads to suppression of endogenous antinociceptive systems, consequently facilitating the trigeminal nociceptive process via up-regulation of the calcitonin gene-related peptide (CGRP) system. Recognizing and preventing its development is an integral aspect of migraine management, as medication overuse is a modifiable risk factor in the progression from episodic to chronic migraine. Over the years, MOH has been difficult to treat and has generated much controversy. Ongoing debates exist over the diagnostic criteria and treatment strategies, particularly regarding the roles of formal detoxification and preventive treatment. The arrival of the anti-CGRP monoclonal antibodies has also challenged our views of MOH and its treatment. This review outlines the evolution of MOH diagnostic criteria, presents the current understanding of MOH pathogenesis and discusses the debates over its development and treatment. Data on the efficacy of anti-CGRP monoclonal antibodies in the setting of medication overuse is also presented. These results indicate that patients with medication overuse, who are treated with these new medications, may not need to be detoxified in order to treat MOH. In light of these developments, it is likely that in the future MOH will be more readily diagnosed and treatment will result in better outcomes.

The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper.

BACKGROUND: In 2006, a US Food and Drug Administration (FDA) alert warned about the potential life-threatening risk of serotonin syndrome when triptans are used in combination with selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephrine reuptake inhibitors (SNRIs). This American Headache Society Position Paper further reviews the available evidence of the potential risk of combining triptans with other serotonergic agents. METHODS: Using the Sternbach Criteria or the Hunter Serotonin Toxicity Criteria, the 29 cases used as the basis for the FDA alert were assessed in addition to a more recently published clinical review of 11 case reports of serotonin syndrome resulting from monotherapy, and one report of combination serotonergic agents. Evidence was evaluated according to the American Academy of Neurology Clinical Practice Guideline Process Manual. RESULTS: Collectively, 40 case reports are available in the literature for subjects receiving either combination or monotherapy of serotonin agonists, all of which are limited to Class IV level of evidence. Of the 29 cases used as the basis for the FDA alert, 10 cases actually met the Sternbach Criteria for diagnosing serotonin syndrome. No cases fulfilled the Hunter Criteria for serotonin toxicity. One case published since the original report does not meet either criteria, and subsequently reported cases involving triptan monotherapy include insufficient details to confirm a diagnosis of serotonin syndrome. RECOMMENDATIONS: With only Class IV evidence available in the literature and available through the FDA registration of adverse events, inadequate data are available to determine the risk of serotonin syndrome with the addition of a triptan to SSRIs/SNRIs or with triptan monotherapy. The currently available evidence does not support limiting the use of triptans with SSRIs or SNRIs, or the use of triptan monotherapy, due to concerns for serotonin syndrome (Level U). However, given the seriousness of serotonin syndrome, caution is certainly warranted and clinicians should be vigilant to serotonin toxicity symptoms and signs to insure prompt treatment. Health care providers should report potential cases to MedWatch and consider submitting them for publication.

Overuse of opioids for acute migraine in an Australian emergency department.

OBJECTIVE: Acute migraine is associated with significant personal, economic and work-related disability. Management guidelines advise the use of simple analgesia, triptans, chlorpromazine and anti-emetics based on severity, with avoidance of opioids. We aimed to determine consistency of prescribing patterns in our ED with national guidelines. METHODS: We performed a retrospective cohort analysis of migraine presentations (ICD-10-AM G439) between 2012 and 2016. Exclusion criteria included migraine without headache, other primary headaches and secondary headaches. Demographic and prescribing data were extracted from medical records. Results have been reported as proportions. RESULTS: Of 4769 headache presentations, the application of exclusion criteria led to a total of 744 patients who received a migraine diagnosis (G439). Most were female (558/744, 75%), young (mean age 36.4 years) and had a self-reported migraine history (558/744, 75%). There were 54 different medications prescribed. Paracetamol was more frequently prescribed (385/744, 52%) than aspirin (134/744, 18%). Opioid prescription occurred in nearly half of all presentations (345/744, 46%). Similar opioid prescriptions were also observed in those with a documented history of migraines (253/558, 45%). A minority of patients received triptans (51/744, 7%). Overall, a quarter of patients (189/744, 25%) received no guideline-recommended medications. CONCLUSION: We observed considerable polypharmacy in ED migraine management with inconsistent prescribing patterns. Recommended medications were infrequently used and opioid use was common. Factors influencing prescribing patterns require further investigation in order to improve rates of guideline recommended treatment.

Complementary and alternative approaches to the treatment of tension-type headache.

Although pharmacotherapy with NSAIDs and tricyclic antidepressants comprises the traditional treatment of tension-type headaches (TTHs), the use of other therapeutic approaches in combination with medications can increase the success of treatment. Patients with comorbid mood disorders and unremitting headaches may particularly benefit from some nonpharmacologic approaches. This review focuses on complementary and alternative approaches to TTH treatment, including psychological therapies, acupuncture, and physical treatments.

Foods and supplements in the management of migraine headaches.

OBJECTIVE: Although a wide range of acute and preventative medications are now available for the treatment of migraine headaches, many patients will not have a significant improvement in the frequency and severity of their headaches unless lifestyle modifications are made. Also, given the myriad side effects of traditional prescription medications, there is an increasing demand for "natural" treatment like vitamins and supplements for common ailments such as headaches. Here, we discuss the role of food triggers in the management of migraines, and review the evidence for supplements in migraine treatment. METHODS: A review of the English language literature on preclinical and clinical studies of any type on food triggers, vitamins, supplements, and migraine headaches was conducted. RESULTS: A detailed nutritional history is helpful in identifying food triggers. Although the data surrounding the role of certain foods and substances in triggering headaches is controversial, certain subsets of patients may be sensitive to phenylethylamine, tyramine, aspartame, monosodium glutamate, nitrates, nitrites, alcohol, and caffeine. The available evidence for the efficacy of certain vitamins and supplements in preventing migraines supports the use of these agents in the migraine treatment. CONCLUSIONS: The identification of food triggers, with the help of food diaries, is an inexpensive way to reduce migraine headaches. We also recommend the use of the following supplements in the preventative treatment of migraines, in decreasing order of preference: magnesium, Petasites hybridus, feverfew, coenzyme Q10, riboflavin, and alpha lipoic acid.

Role of magnesium in the pathogenesis and treatment of migraine.

Magnesium is an important intracellular element that is involved in numerous cellular functions. Deficiencies in magnesium may play an important role in the pathogenesis of migraine headaches by promoting cortical spreading depression, alteration of neurotransmitter release and the hyperaggregation of platelets. Given this multifaceted role of magnesium in migraine, the use of magnesium in both acute and preventive headache treatment has been researched as a potentially simple, inexpensive, safe and well-tolerated option. Studies have shown that preventive treatment with oral magnesium and acute headache treatment with intravenous magnesium may be effective, particularly in certain subsets of patients. In this review, the pathogenesis of migraine will be discussed, with an emphasis on the role of magnesium. Studies on the use of intravenous and oral magnesium in migraine treatment will be discussed and recommendations will be made regarding the use of magnesium in treating migraine headaches.

Drug-induced serotonin syndrome: a review.

Serotonin syndrome, or serotonin toxicity (ST), is a clinical condition that occurs as a result of an iatrogenic drug-induced increase in intrasynaptic serotonin levels primarily resulting in activation of serotonin(2A) receptors in the central nervous system. The severity of symptoms spans a spectrum of toxicity that correlates with the intrasynaptic serotonin concentration. Although numerous drugs have been implicated in ST, life-threatening cases generally occur only when monoamine oxidase inhibitors are combined with either selective or nonselective serotonin re-uptake inhibitors. The triad of clinical features consists of neuromuscular hyperactivity, autonomic hyperactivity and altered mental status, which may present abruptly and progress rapidly. The awareness of ST is crucial not only in avoiding the unintentional lethal combination of therapeutic drugs but also in recognizing the clinical picture when it occurs so that treatment can be promptly initiated. In this review, the pathophysiology, clinical features, implicated drugs, diagnosis and treatment of ST are discussed.

Cluster headache in women.

Cluster headache has long been considered a predominantly male disorder, with much of our knowledge based on studies of men. However, it has become increasingly more recognized in women. Although there are many similarities between men and women in the expression of the disorder, studies over the years have revealed gender differences. This article reviews epidemiologic, clinical, hormonal, and familial differences between male and female cluster patients, examines how they may affect treatment, and suggests studies that may give us a better understanding of the disorder.