Dilemma regarding acute medication during a migraine attack - “Yes, it will be fine; I’ll have a cup of coffee”

Objective The aim of this study was to explore patients’ experiences and management of pain in connection with a migraine attack in episodic migraine. Design, setting and subjects This qualitative study used a semi-structured interview format based on functional behavioural analysis as commonly used in cognitive behavioural therapy. We interviewed eight participants and analysed their responses using systematic text condensation. Results Participants’ descriptions of their experiences and management of pain from episodic migraine were sorted into three description First physical sensations, Automatic reactions and Acts according to the interpretation. Conclusion From a biopsychosocial perspective, a migraine attack is much more complex than just an experience of pain. The purely biological pain prompts a number of automatic reactions leading to strategies for pain management.

MIGRAINE PATHOPHYSIOLOGY

Clinical Guidelines19 November 2002Pharmacologic Management of Acute Attacks of Migraine and Prevention of Migraine HeadacheFREEVincenza Snow, MD, Kevin Weiss, MD, Eric M. Wall, MD, MPH, and Christel Mottur-Pilson, PhD, for the American Academy of Family Physicians and the American College of Physicians–American Society of Internal Medicine*Vincenza Snow, MDFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., Kevin Weiss, MDFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., Eric M. Wall, MD, MPHFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., and Christel Mottur-Pilson, PhDFrom American Academy of Family Physicians, Leawood, Kansas; Hines Veterans Affairs Medical Center and Northwestern University Feinberg School of Medicine, Chicago, Illinois; and American College of Physicians–American Society of Internal Medicine, Philadelphia, Pennsylvania., for the American Academy of Family Physicians and the American College of Physicians–American Society of Internal Medicine*Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-137-10-200211190-00014 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Migraine headache is a common disorder seen in primary care. It affects 18% of women and 6.5% of men in the United States, almost half of whom are undiagnosed or undertreated (1, 2). These guidelines, developed by the American Academy of Family Physicians and the American College of Physicians–American Society of Internal Medicine, with assistance from the American Headache Society, are based on two previously published papers (3, 4). The papers, titled "Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management of Acute Attacks," by Matchar and colleagues (3), and "Evidence-Based Guidelines for Migraine Headache in the Primary Care Setting: Pharmacological Management for Prevention of Migraine," by Ramadan and coworkers (4), can be found at www.aan.com/professionals/practice/guidelines.cfm. 1 The target audience for this guideline is primary care physicians. The guideline applies to patients with acute migraine attacks, with or without aura, and patients with migraine who are candidates for preventive drug therapy. Although these guidelines are all based on the articles by Matchar and Ramadan and colleagues, the recommendations may differ because different thresholds of evidence were needed for making a positive recommendation. Table 1 compares the AAFP/ACP–ASIM guideline and the U.S. Headache Consortium Guideline.Table 1. Summary of U.S. Headache Consortium Recommendations Compared with AAFP/ACP–ASIM RecommendationsThroughout the text, asterisks indicate drugs that are currently not available in the United States.DiagnosisHeadache has many potential causes. Most headaches are caused by the primary headache disorders, which include migraine, cluster, and tension-type headaches. Secondary headaches, which are those with underlying pathologic causes, are far less common. Migraine is a chronic condition with recurrent acute attacks whose characteristics vary among patients and often among attacks within a single patient. Migraine is a syndrome with a wide variety of neurologic and non-neurologic manifestations. The International Headache Society (6) has developed diagnostic criteria for migraine with and without aura (Appendix Table 1). This classification system serves to diagnose headache syndromes, not patients. Thus, one patient could have more than one type of headache disorder. For example, it is not uncommon for migraine patients to also have episodic tension-type headaches.Management of Acute AttacksEffective long-term management of patients with migraine is challenging because of the complexity of the condition. Experts suggest several goals for successful treatment of acute attacks of migraine. These include treating attacks rapidly and consistently to avoid headache recurrence, to restore the patient's ability to function, and to minimize the use of backup and rescue medications.Clinicians need to educate people with migraine about their condition and its treatment and encourage them to participate in their own management. The physician must help the patient establish realistic expectations by discussing therapeutic options and their benefits and harms. Patient input can provide the best guide to treatment selection and helps the physician to better understand and accommodate patient treatment goals. Developing an effective acute migraine management strategy can be complex, and an engaged patient is more likely to negotiate this process successfully. Encouraging patients to identify and avoid triggers (Table 2) and to be actively involved in their own management by tracking their own progress may be especially useful.Table 2. Some Commonly Reported Triggers of Migraine HeadacheOnce a diagnosis of migraine is established, patients and their health care providers should decide together how to treat acute attacks and whether the patient is a candidate for preventive medications. A wide range of acute treatments with varying efficacies is currently in use (Appendix Table 2). A comprehensive review of the scientific literature, especially the data from randomized, controlled trials, provides a list of treatments that have demonstrated efficacy in the management of acute migraine headache. It also provides a clear understanding of the adverse events associated with various agents.The Headache Consortium's review of the evidence on antiemetics, barbiturate hypnotics, ergot alkaloids and derivatives, nonsteroidal anti-inflammatory drugs (NSAIDs), combination analgesics and nonopiate analgesics, opiate analgesics, triptans, and other agents found good evidence of the efficacy of only a few agents in the treatment of acute migraine (3).Available AgentsNSAIDsTheir demonstrated efficacy and favorable tolerability make NSAIDs a first-line treatment choice for all migraine attacks, including severe attacks that have responded to NSAIDs in the past. Among the NSAIDs, the most consistent evidence exists for aspirin (8-10), ibuprofen (11, 12), naproxen sodium (13, 14), tolfenamic acid* (8, 15), and the combination agent acetaminophen plus aspirin plus caffeine for the acute treatment of migraine (16). The evidence shows that acetaminophen alone is ineffective (17).Serotonin1B/1D Agonists (Triptans)There is good evidence for the effectiveness of the oral triptans naratriptan (18, 19), rizatriptan (20-23), sumatriptan (24-31), and zolmitriptan (32-34). In addition, there is good evidence for the effectiveness of subcutaneous (35-38) and intranasal (39-41) sumatriptan, making it an option for patients with nausea and vomiting. Adverse effects of the triptans include chest symptoms, but postmarketing data indicate that true ischemic events are rare. Triptans are contraindicated in patients with risk for heart disease, basilar or hemiplegic migraine, or uncontrolled hypertension. Subcutaneous sumatriptan is associated with a very rapid onset of action, and oral naratriptan is associated with a slower onset of action.ErgotaminesThere is good evidence for the efficacy and safety of intranasal dihydroergotamine (DHE) as monotherapy for acute migraine attacks (42-46). Placebo-controlled studies of intravenous DHE did not clearly establish its efficacy in the acute treatment of migraine (47, 48). The evidence was inconsistent to support efficacy of ergotamine or ergotamine–caffeine, and the studies documented frequent adverse events.OpioidsIt is well recognized that opiates are good analgesics, but there is good evidence only for the efficacy of butorphanol nasal spray (49, 50). Although opioids are commonly used, surprisingly few studies of opioid use in headache pain document whether overuse and the development of dependence are as frequent as clinically perceived. Until further data are available, these drugs may be better reserved for use when other medications cannot be used, when sedation effects are not a concern, or the risk for abuse has been addressed.Other AgentsFair evidence suggests that the antiemetic metoclopramide, given intravenously, may be an appropriate choice as monotherapy for acute attacks (51-53), particularly in patients with nausea and vomiting when the sedating side effect may also be useful. Isometheptene and isometheptene combinations obtained only borderline significance in relieving headache pain (17, 54, 55). Other agents used in practice, such as intravenous corticosteroids and intranasal lidocaine, are not effective.Choice of TreatmentSince patient responses to these therapies are not always predictable, individualized management is important. The choice of treatment should be based on, among other characteristics, the frequency and severity of attacks; the presence and degree of temporary disability; and the profile of associated symptoms, such as nausea and vomiting. The patient's history of, response to, and tolerance for specific medications must also be considered. Coexisting conditions (such as heart disease, pregnancy, and uncontrolled hypertension) may limit treatment choices.No studies document the effectiveness of specific treatment schedules, but experts suggest that acute therapy should be limited to no more than two times per week to guard against medication-overuse headache (or drug-induced headache). Medication-overuse headache is thought to result from frequent use of acute medication and has a pattern of increasing headache frequency, often resulting in daily headaches. In patients with suspected medication overuse or patients at risk for medication overuse, preventive migraine therapy should be considered.Although some use the term rebound headache interchangeably with the term medication-overuse headache, rebound headache is a distinct entity. Rebound headache is associated with withdrawal of analgesics or abortive migraine medication. There is no uniform agreement about which agents can cause rebound headache, although ergotamine (not DHE); opiates; triptans; and simple and mixed analgesics containing butalbital, caffeine, or isometheptene are generally thought to do so. There is less uniform opinion about other antimigraine agents.Another clinical consideration is the use of a self-administered rescue medication for patients with severe migraine attack that is not responding to (or failing) other treatments. A rescue medication is an agent such as an opioid or a butalbital-containing compound that the patient can use at home when other treatments have failed. Although rescue medications often do not completely eliminate pain and allow patients to return to normal activities, they permit the patient to achieve relief without the discomfort and expense of a visit to the physician's office or emergency department. A cooperative arrangement between provider and patient may extend to the use of rescue medication in appropriate situations.Summary of Treatment of Acute MigraineA body of evidence now points to effective first- and second-line agents for acute treatment of migraine. Beyond the choice of agent lies the choice of management strategy. Recently, interest and research in step care versus stratified care have increased. Step care refers to the initial use of safe, effective, and inexpensive medications as first-line agents in acute attacks of any severity. If the initial agent fails, a second-line, more expensive, migraine-specific medication is then used. The stratified care model initially stratifies migraine attacks by severity, advocating migraine-specific agents for moderate to severe attacks, regardless of previous response to or an unknown response to other agents. Which approach is more effective is still an open question (56).Management of Migraine with Preventive TherapyOnce patients and their health care providers decide how to treat acute attacks, use of preventive medications should be considered. Generally accepted indications for migraine prevention include 1) two or more attacks per month that produce disability lasting 3 or more days per month; 2) contraindication to, or failure of, acute treatments; 3) the use of abortive medication more than twice per week; and 4) the presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction. Other factors to consider are adverse events with acute therapies, patient preference, and the cost of both acute and preventive therapies. (The U.S. Headache Consortium also produced a document on behavioral and other nonpharmacologic therapies for headache prevention, which can be found at www.aan.com/professionals/practice/guidelines.cfm.)A wide range of preventive treatments with varying efficacies is currently in use (Appendix Table 3). A comprehensive review of the scientific literature, especially the data from randomized, controlled trials, provides a list of treatments that have demonstrated efficacy in the prevention of migraine headache. It also provides a clear understanding of the adverse events associated with various agents. The Headache Consortium's review of the evidence on α2-agonists, anticonvulsants, antidepressants, β-blockers, calcium-channel blockers, NSAIDs, serotonergic agents (ergot derivatives, methysergide, and others), hormone therapy, feverfew, magnesium, and riboflavin found that there was good evidence of the efficacy of only a few agents in migraine prevention. A summary of these results follows.Available Agentsβ-BlockersEvidence consistently showed the efficacy of propranolol, 80 to 240 mg/d (57-63), and timolol, 20 to 30 mg/d (63-65), for the prevention of migraine. One trial comparing propranolol and amitriptyline suggested that propranolol is more efficacious in patients with migraine alone; amitriptyline was superior for patients with mixed migraine and tension-type headache (66). There is limited evidence of a moderate effect for atenolol (67, 68), metoprolol (69-71), and nadolol (72-74). β-Blockers with intrinsic sympathomimetic activity (acebutolol, alprenolol, oxprenolol, pindolol) seem to be ineffective for the prevention of migraine. Adverse effects reported most commonly with β-blockers were fatigue, depression, nausea, dizziness, and insomnia. These symptoms appear to be fairly well tolerated and seldom caused premature withdrawal from trials.AntidepressantsAmitriptyline has been more frequently studied than the other antidepressants and is the only one with consistent support for efficacy in migraine prevention (75-77). The dosages that were most efficacious in the clinical trials ranged from 30 to 150 mg/d. Drowsiness, weight gain, and anticholinergic symptoms were frequently reported with the tricyclic antidepressants studied, including amitriptyline. There is no evidence for the use of nortriptyline, protriptyline, doxepin, clomipramine, or imipramine. There is limited evidence of a modest effect for fluoxetine at dosages ranging from 20 mg every other day to 40 mg per day (78, 79). There is no evidence from controlled trials for the use of fluvoxamine, paroxetine, sertraline, phenelzine, bupropion, mirtazapine, trazodone, or venlafaxine.AnticonvulsantsFor the anticonvulsants, there is good evidence for the efficacy of divalproex sodium (80-82) and sodium valproate (83, 84). Adverse events with these therapies are not uncommon and include weight gain, hair loss, tremor, and teratogenic potential, such as neural tube defects. These agents may be especially useful in patients with prolonged or atypical migraine aura. Carbamazepine and vigabatrin* have been shown to be ineffective, and there is limited evidence for moderate efficacy of gabapentin (85).NSAIDsA meta-analysis (4) of five of seven placebo-controlled trials of naproxen or naproxen sodium showed a modest effect on headache prevention (62, 86-92). Similar trends were observed in single placebo-controlled trials of flurbiprofen, indobufen*, ketoprofen, lornoxicam*, and mefenamic acid and in two trials of tolfenamic acid*. Placebo-controlled trials of aspirin, aspirin plus dipyridamole, fenoprofen, and indomethacin were inconclusive. There is no evidence for the use of ibuprofen or nabumetone in the prevention of migraine.Side effect rates for naproxen were not significantly higher than those seen with placebo. The most commonly reported adverse events with all NSAIDs were gastrointestinal symptoms, including nausea, vomiting, gastritis, and blood in the stool. In the trials reviewed, such symptoms were reported by 3% to 45% of participants (86).Serotonergic AgentsOf these agents, time-released DHE* had the strongest support, with consistently positive findings in four placebo-controlled trials (93-96). Evidence is insufficient for the efficacy of ergotamine or ergotamine plus caffeine plus butalbital plus belladonna alkaloids or methylergonovine for migraine prevention. Limited information was reported on adverse events associated with these agents. The most commonly reported events for all the ergot alkaloids were gastrointestinal symptoms.There is strong evidence for the efficacy of methysergide (97-100), a semisynthetic ergot alkaloid. However, there are reports of retroperitoneal and retropleural fibrosis associated with long-term, mostly uninterrupted administration. The manufacturer suggests that methysergide therapy be discontinued for 3 to 4 weeks after each 6-month course of treatment. Other adverse events most commonly reported included gastrointestinal symptoms and leg symptoms (restlessness or pain).Other serotonergic agents that have been evaluated for the prevention of migraine include pizotifen*, lisuride*, oxitriptan*, iprazochrome*, and tropisetron*. Only lisuride (101-104) and pizotifen (87, 99, 105-110) have consistent evidence that supports their efficacy in the prevention of migraine. Published data on adverse events associated with lisuride are limited, and pizotifen is often associated with weight gain and drowsiness.Calcium-Channel BlockersThe evidence for nifedipine, nimodipine, cyclandelate*, and verapamil is poor quality and difficult to interpret, suggesting only a modest effect (see reference 4 for study references). There is no evidence for the use of diltiazem in the prevention of migraine. Symptoms reported with these agents included dizziness, edema, flushing, and constipation.Flunarizine*, 10 mg/d, has proven efficacy in the prevention of migraine and is commonly used in countries where it is available (111-115). Adverse events reported with flunarizine include sedation, weight gain, and abdominal pain. Depression and extrapyramidal symptoms can be observed, particularly in elderly persons.α2-AgonistsThere is good evidence for the lack of efficacy of the α2-agonist clonidine in the prevention of migraine (116-120). Limited evidence shows moderate efficacy of guanfacine (121).Hormone Therapy, Feverfew, Magnesium, and RiboflavinThere is fair evidence for modest efficacy of these agents in certain circumstances, but more trials need to be done. Most of the existing trials had small sample sizes, had self-referred or special patient samples, or had other methodologic flaws (see reference 4 for more details and references).Summary of Preventive TherapyTo alleviate the suffering of many patients with migraine, clinicians need to be aware of the commonly accepted indications for preventive therapy and initiate effective therapy in those patients. Although many agents are available for the preventive treatment of migraine, only a few have proven efficacy. Once an agent has been chosen, clinicians should initiate therapy with a low dose and titrate the dose slowly up until clinical benefits are achieved in the absence of adverse events or until limited by adverse events. Because a clinical benefit may take as long as 2 to 3 months to manifest, each treatment should be given an adequate trial. Once preventive treatment is under way, interfering medications, such as overused acute medications such as ergotamine, should be avoided. After a period of stability, clinicians should consider tapering or discontinuing treatment. Patient and clinician need to engage in an ongoing dialogue in which patient expectations and goals for therapy are taken into account when agents are chosen, titrated, or discontinued.RecommendationsRecommendation 1: For most migraine sufferers, nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line therapy.To date, the most consistent evidence exists for aspirin, ibuprofen, naproxen sodium, tolfenamic acid*, and the combination agent acetaminophen plus aspirin plus caffeine. There is no evidence for the use of acetaminophen alone.Recommendation 2: In patients whose migraine attack has not responded to NSAIDs, use migraine-specific agents (triptans, DHE).There is good evidence for the following triptans: oral naratriptan, rizatriptan, and zolmitriptan; oral and subcutaneous sumatriptan; and DHE nasal spray. Few data in the literature demonstrate which triptans are more effective. Oral opiate combinations and butorphanol may be considered in acute migraine when sedation side effects are not a concern and the risk for abuse has been addressed.Recommendation 3: Select a nonoral route of administration for patients whose migraines present early with nausea or vomiting as a significant component of the symptom complex. Treat nausea and vomiting with an antiemetic.Evidence is limited, but in some patients, concomitant treatment with an antiemetic and an oral migraine medication may be appropriate. Antiemetics should not be restricted to patients who are vomiting or likely to vomit. Nausea itself is one of the most aversive and disabling symptoms of a migraine attack and should be treated appropriately.Recommendation 4: Migraine sufferers should be evaluated for use of preventive therapy.Generally accepted indications for migraine prevention include 1) two or more attacks per month that produce disability lasting 3 or more days per month; 2) contraindication to, or failure of, acute treatments; 3) use of abortive medication more than twice per week; or 4) the presence of uncommon migraine conditions, including hemiplegic migraine, migraine with prolonged aura, or migrainous infarction.Recommendation 5: Recommended first-line agents for the prevention of migraine headache are propranolol (80 to 240 mg/d), timolol (20 to 30 mg/d), amitriptyline (30 to 150 mg/d), divalproex sodium (500 to 1500 mg/d), and sodium valproate (800 to 1500 mg/d).Medications with proven efficacy but limited published data on adverse events or frequent or severe adverse events include flunarizine*, lisuride*, pizotifen*, time-released and migraine sufferers about the of acute attacks and preventive therapy and engage them in the of a management should be on a is strong about the need for people with migraine. The physician must help the patient establish realistic expectations by discussing therapeutic options and their benefits and such as medication-overuse headache. Encouraging patients to be actively involved in their own management by tracking their own progress daily for example, may be especially useful. should attack frequency, severity, and resulting disability; response to type of and adverse effects of medication. Patient input can provide the best guide to treatment Table 1. International Headache Society Table 2. Summary of the Evidence for Acute Table Summary of the Evidence for Preventive M. and of migraine in the United data from the American Migraine Migraine diagnosis and results from the American Migraine Matchar guidelines for migraine headache in the primary care management of acute at www.aan.com/professionals/practice/guidelines.cfm. Ramadan guidelines for migraine headache in the primary care management for prevention of migraine. at www.aan.com/professionals/practice/guidelines.cfm. Matchar guidelines for migraine of and at www.aan.com/professionals/practice/guidelines.cfm. and diagnostic criteria for headache disorders, and pain. Headache of the International Headache and diagnosis of Headache in Clinical Medical acid is as effective as ergotamine migraine of an acetaminophen mg combination versus aspirin mg and in acute migraine and aspirin versus aspirin or for migraine a Treatment of acute migraine ibuprofen and A study of ibuprofen versus in the treatment of acute migraine a migraine naproxen sodium ergotamine plus caffeine. M. sodium in the treatment of migraine. metoclopramide, caffeine and their combinations in the treatment of migraine and safety of aspirin, and caffeine in migraine headache randomized, placebo-controlled Treatment of migraine with and a trial. is effective and well tolerated in the acute treatment of migraine. of a is effective and well tolerated in the acute treatment of migraine. of a The study of in migraine. sumatriptan in the acute treatment of migraine. A study of rizatriptan in the acute treatment of migraine.

Previous studies have reported health utilities for migraine patients as generally measured between migraine attacks, but health utility data for within a migraine attack are unavailable. We evaluated within-attack health utilities among acute migraine patients experiencing different grades of headache severity. We examined data for 330 20-65-year-old adults, in good physical health, who had 1-6 moderate/severe migraine attacks per month in the 2 months prior to the screening visit. Data were collected from a multicenter, double-blind study of a treatment for acute migraine in the United States. The EQ-5D system was used to measure generic health status at baseline and 24 h post-treatment within an acute migraine attack, and patients were also asked to rate their pain level at these time points (no, mild, moderate, or severe pain). The D1 time-trade-off scoring algorithm for the U.S. population was applied. Confidence intervals were estimated by bootstrap methods. The study population was 88% women and 78% white ethnicity, with 60% of subjects over age 40. The disutility of mild migraine pain was estimated to be 0.140 (95% CI: 0.0848, 0.1940), with a disutility for moderate migraine pain of 0.186 (95% CI: 0.1645, 0.2053) and for severe migraine pain of 0.493 (95% CI: 0.4100, 0.5654). Within-attack disutilities estimated for migraine in this study are much greater than those reported for migraine when evaluated as a chronic health condition (e.g., valuations collected at random time points). These data can be of value in adapting results from clinical trials of migraine interventions to cost-utility policy analyses.

ABSTRACT:Objectives:To provide an overview of the objectives and target population of the guideline, and to review the general principles of acute pharmacological migraine therapy.Methods:A general literature review and several consensus groups were used to formulate an expert consensus for the general use of acute migraine medications.Results:The objective of the guideline is to assist the physician in choosing an appropriate acute migraine medication for an individual with migraine, and thereby to reduce migraine-related disability. The target population includes adults with episodic migraine (patients with migraine headache < 15 days/month). This guideline is intended primarily for physicians who treat patients with migraine. Other health professionals may also find this guideline helpful. Acute migraine therapy should be considered for the great majority of patients with migraine. A specific acute medication is chosen based on evidence for efficacy, tolerability, migraine attack severity, patient preference, and on the presence of co-existing disorders. General principles of acute migraine therapy include that the response of a patient to any given medication cannot be predicted with certainty, and that treatment early in the attack is generally more effective than treatment later once the migraine attack is fully developed. A suitable treatment approach (stratified or stepped approaches) and drug formulation (injection, tablet, wafer, powdered formulation, or nasal spray) should be chosen based on patient clinical features. Excessively frequent use of acute medications (medication overuse) should be avoided. Two or more acute medications can be combined if necessary.Conclusions:This guideline provides evidence-based advice on the use of acute medications for migraine, and should provide useful guidance for acute migraine therapy to both health professionals and patients.

There is no question that significant vascular changes may occur during a migraine attack. The question is whether these vascular phenomena are a cause or a consequence of migraine pathophysiology and migraine symptoms. While the simplistic appeal of the ‘vascular hypothesis’ of migraine has had remarkable staying power, studies of the clinical features of migraine, and its physiological and pharmacological mechanisms, have provided strong evidence that effectively refutes a primary role for the vasculature in migraine pathogenesis. It is important to start with the concept of migraine as not merely a headache, but rather a multi-faceted clinical phenomenon that can occur over hours to days. Diverse prodromal symptoms including yawning, mood change, neck pain and polyuria, among others, are common, and electronic diary studies have shown that these symptoms may occur up to several hours before the onset of headache (1). Aura symptoms include both positive and negative visual phenomena, and characteristic sensory or language dysfunction. Nausea, light and sound sensitivity, mechanical allodynia, vertigo and fatigue commonly occur before, during, or after headache. These symptoms indicate elaborate changes in brain chemistry and physiology – there is no reasonable explanation of these symptoms based on a primary vascular mechanism. Regarding migraine headache, the ‘vascular hypothesis’ is centered on the premise that migraine pain is caused by vasodilation. A variety of imaging and pharmacological studies, however, have directly challenged this concept. Pioneering blood flow studies performed by Olesen and colleagues (2) found that a migraine attack may include both hypoand hyperperfusion phases. These studies found that the headache component of the attack begins during the hypoperfusion phase and continues into the hyperperfusion phase, but the hyperperfusion may continue long after the headache has ended. Put simply, there is no correlation between blood flow changes and headache. Recent magnetic resonance angiography (MRA) studies have similarly shown no correlation between changes in vascular caliber and headache in either evoked or spontaneous migraine. Schoonman et al. (3) found that while nitroglycerin did evoke some cerebral and meningeal vasodilation, migraine headache did not occur until after the caliber of vessels had returned to baseline. Nagata et al. (4) reported that spontaneous migraine was not associated with any dilation of the middle meningeal artery as measured by MRA. Rahmann and colleagues (5) showed that vasoactive intestinal peptide is a potent dilator of cerebral vessels, yet does not cause headache. Conversely, sildenafil is known to evoke headache and migraine, but does not cause cerebral vasodilation or alteration in cerebrovascular function (6). Taken together, these studies clearly indicate that vasodilation is neither necessary nor sufficient to cause migraine headache. It has also long been assumed that the pulsating quality of migraine pain is a reflection of vascular pulsation. Recent studies by Ahn (7), however, call this assumption into question, suggesting that in most patients the rate of migraine pain pulsation is in fact slower than the arterial pulse rate. In some patients, the rates of pain pulsation were similar to the arterial pulse, but the two rates were observed to come in and out of phase over time. These studies raise the possibility that pain pulsation could be driven by a mechanism involving neural oscillations rather than by perception of the arterial pulse. Multiple acute and preventive medications such as caffeine, ergotamines, triptans, beta-blockers and

This pilot study explored the potential for 2 recognized acute migraine medications, 85 mg of sumatriptan plus 500 mg of naproxen sodium in a combination tablet (SumaRT/Nap) and 500 mg of naproxen sodium, to treat and modify the disease progression of migraine. In other words, can these medications both abort an acute attack of migraine and reduce the number of future migraine attacks? Patients suffering with moderate to severe attacks of migraine desire acute treatment. As migraine frequency increases, so does the need for more frequent relief of acute attacks. This may lead to medication overuse and potentially medication overuse headache (MOH). Ideally, acute medication would have the ability to abort an attack of migraine and reduce the likelihood of future attacks. The primary endpoint of this study was a reduction in migraine headache days from baseline through month 3 of the study. Subjects were randomized 1:1 to treat 14 or fewer migraines per month with SumaRT/Nap (Group A) or naproxen sodium (Group B) for 3 months. Subjects in group A utilized SumaRT/Nap were encouraged, but not required, to treat migraine headache within 1 hour of onset of headache when the pain was mild. They could re-treat if needed after 2 hours. Subjects in group B utilized the same treatment strategy with 500 mg of naproxen sodium. Tablets of study medication were identical for both groups. Subjects recorded headache days, migraine attacks, duration of attacks, treatment, and treatment results daily on paper diaries. Subjects took the Migraine Disability Assessment Test (MIDAS) at randomization and 3 months later at the end of study. Naproxen sodium was associated with a statistically significant reduction in migraine headache days at month 3 compared to baseline (P = .0002). SumaRT/Nap was also associated with a reduction of migraine headache days, but this decrease did not reach statistical significance (P = .2). In addition, subjects in the naproxen sodium group had a statistically significant reduction of migraine attacks in all 3 months of the study compared to baseline. A greater than 50% reduction in the number of migraine headache days at month 3 occurred in 43% (6/14) of subjects in group B compared to 17% (3/18) of subjects in group A. Consistent with large regulatory studies comparing the efficacy of SumaRT/Nap with naproxen sodium, SumaRT/Nap in this study was statistically superior to naproxen sodium at 2 hours in reducing headache severity during months 2 and 3. There was a reduction of acute medication used from baseline to month 3 and improvement in MIDAS scores for both groups. Naproxen sodium, when used as a sole acute treatment early in attacks, appears to reduce the frequency of headache days and migraine attacks for a select number of subjects over a 3-month period. SumaRT/Nap is more effective at 2-hour headache reduction than naproxen sodium alone, but has less impact on reducing attack frequency or the number of headache days. Both treatments were well tolerated, and there was no convincing evidence that either medication led to MOH.

Migraine is often associated with health consequences including impaired quality of life, and the cost of treating migraine headaches places a significant financial burden on patients who suffer from migraines. Nonsteroidal anti-inflammatory drugs (NSAIDs) and triptans are commonly used for the treatment of acute migraine attacks. Aspirin is widely accepted as a treatment option for migraine pain relief and could provide an alternative not only for treatment of moderate migraine attacks, but also for severe migraine attacks. The efficacy and safety of 1,000 mg effervescent aspirin (eASA) was evaluated in comparison to 50 mg sumatriptan and placebo in an individual patient data meta-analysis of three randomized, placebo-controlled, single- dose migraine trials. Pain-relief at 2 h, pain-free at 2 h and sustained pain-free up to 24 h were calculated. For eASA, the response rates were 51.5 % (95 % CI: 46.6-56.5 %), 27.1 % (95 % CI: 22.6-31.4 %), and 23.5 % (95 % CI: 19.3-27.7 %). For sumatriptan, the response rates were 46.6 % (95% CI: 40.0-53.2 %), 29% (95 % CI: 23.0-34.9 %), and 22.2 % (95 % CI: 16.7-27.6 %). The corresponding rates for placebo were 33.9 % (95% CI: 29.1-38.6 %), 15.1 % (95 % CI: 11.5-18.7 %), and 14.6 % (95 % CI: 11.0-18.1 %). The treatment effect of eASA and sumatriptan were significantly different from placebo (p < 0.001), but differences between eASA and sumatriptan were not significant. The remission of accompanying symptoms and the subgroup analyses of patients with moderate or severe migraine pain at baseline revealed no significant differences between eASA and sumatriptan. Safety was evaluated based on the frequency of reported adverse events, and treatment with eASA was associated with lower incidence of adverse events than was with sumatriptan. This individual patient data meta-analysis provided evidence that eASA 1,000 mg is as effective as sumatriptan 50mg for the treatment of acute migraine attacks and has a better side effect profile. This is also true for patients with moderate as well as severe headache at baseline. Patients therefore should be advised to use eASA first for migraine attacks and use a triptan in case of no response.

To determine whether treatment of migraine with almotriptan, when pain intensity is mild, improves 1- and 2-hour pain-free and sustained pain-free rates compared with treatment when pain intensity is moderate or severe. This was a post hoc analysis derived from an open-label, multicenter, long-term study of the safety, tolerability, and efficacy of almotriptan 12.5 mg. Patients who met International Headache Society criteria for migraine with or without aura were eligible. Patients were instructed to take a single dose of almotriptan 12.5 mg at the onset of a migraine attack. Rescue medication could be taken if migraine pain had not disappeared at 2 hours. A second dose of almotriptan 12.5 mg could be taken if head pain recurred within 24 hours of the initial dose. Patients reported the intensity of pain at baseline and at 1 and 2 hours postmedication using a 4-point scale: no pain, mild, moderate, or severe pain. They also reported recurrence of pain (return of moderate or severe pain within 2 to 24 hours of taking the study medication) and use of rescue medication. Rescue medication consisted of supplemental analgesics taken for pain relief at 2 to 24 hours postdose. Ergotamines and other 5-HT1B/1D agonists were excluded as rescue medications. Based on these patient-reported end points, sustained pain-free rates, defined as pain-free at 2 hours with no recurrence from 2 to 24 hours and no use of rescue medication, were calculated. A higher proportion of migraine attacks of mild intensity were pain-free at 1 hour (35.3%) compared with attacks of moderate or severe intensity (7.5%) (P <.001). Two-hour pain-free rates also were significantly higher with mild intensity pain (76.9%) compared to moderate or severe intensity (43.9%) (P <.001). In addition, recurrence rates and use of rescue medication were reduced when attacks were treated during mild pain. Recurrence was 12.9% for mild pain versus 25.0% for moderate or severe pain (P <.001), and use of rescue medication was 9.4% for mild pain versus 17.2% for moderate or severe pain (P <.001). Sustained pain-free rates were nearly twice as high when attacks were treated during mild intensity pain (66.6%) compared with attacks treated during moderate or severe pain (36.6%) (P <.001). Treatment with almotriptan 12.5 mg during migraine attacks of mild pain intensity improves 1- and 2-hour pain-free and sustained pain-free responses.

REVIEW QUESTION / OBKECTIVE The qualitative objective of this systematic review is to identify and synthesize the best available evidence on experiences of acute non-surgical pain, including pain management, of children (between four to 18 years) when they present to a healthcare facility for treatment. The specific objectives are to identify: Children’s experiences of their acute, non-surgical pain, including pain management Children’s expectations of others in managing their acute, non-surgical pain including, but not limited to parents and nurses INCLUSION CRITERIA Types of participants This review will consider studies that include children aged four to 18 years who present to a healthcare facility for treatment of their acute (less than three months), non-surgical pain caused by any injury or medical condition. Children younger than four years typically have not developed linguistic skills that enable them to articulate their experiences. Phenomena of interest This review will consider studies that explore children’s experiences of acute, non-surgical pain and their expectations of other people in managing their pain, including, but not limited to, parents and nurses. Studies focusing on children with postoperative pain or those reporting on children with chronic pain will be excluded. Context Any healthcare facility, including, but not limited to, general practitioners, hospitals, emergency departments and outpatient clinics will be considered.

Eptinezumab is an intravenous anti-calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) approved for the prevention of episodic and chronic migraine. We aimed to explore the earliest changes in migraine pain intensity and associated symptoms during the first 30 min of eptinezumab infusion in a real-world setting, particularly when an acute migraine attack was ongoing. The BE-FREE study is an ongoing Italian observational, multicenter, independent, real-world, and prospective study. We enrolled patients affected with episodic migraine (EM) and chronic migraine (CM) who were experiencing an ongoing migraine attack. Eptinezumab was administered within 1-12 h of the onset of the qualifying migraine attack. Data collected included monthly migraine days (MMDs), headache pain intensity, the number of monthly acute medications, and the use of concomitant or past standard preventive treatments (SPTs). The Numerical Rating Scale (NRS), associated symptoms, and pain freedom (PF) were recorded before infusion (T0) and at intervals of 10 (T10), 20 (T20), and 30 (T30) min during infusion. We enrolled 31 patients (87% female), with a mean age of 43.1 years (SD 2.7); of these, 68% had CM. NRS scores significantly reduced at T10 (p = 0.011) and T20 (p = 0.004). Photophobia was less frequent at T10 (p = 0.045), phonophobia at T20 (p = 0.014), and osmophobia at T30 (p = 0.046) compared with T0. PF was reported by 6.5% of patients at T10, 19.4% at T20, 29.0% at T30, and 19.4% at T60, T90, and T120. The BE-FREE study results, representing the first real-world evidence, demonstrate the rapid effect of eptinezumab during the first 30 min of infusion in patients experiencing an ongoing migraine attack.

Pre-emptive/early intervention with triptans in migraine: hope, hype and hazard

Clinicians’ Practices In Pain Assessment And Management For Elderly With Heart Failure

Cephalic and extracephalic allodynia are recognized as a common sign of sensory sensitization during migraine episodes. However, the occurrence of body pain in migraine has not been thoroughly explored. Here we report three patients presenting with spontaneous body pain in association with migraine attacks. A 41-year-old woman experienced face and limb pain along with migraine headaches; it started before, during or after headache, was usually ipsilateral to head pain, and could last from minutes to days. A 39-year-old woman had pain in her right limbs, back and neck for 30-60 min prior to right-sided migraine headaches. A 30-year-old woman perceived pain in her left upper limb for 24-48 h prior to left-sided migraine headaches. All patients had allodynia to mechanical stimuli over the painful areas. Spontaneous body pain may be associated with migraine attacks. Together with allodynia, this might be a consequence of central sensitization.

To prospectively assess 1) the incidence and duration of postdural puncture headache (PDPH) in migraineurs and healthy subjects; 2) the associated risk factors; and 3) the risk of getting a migraine attack shortly before or after lumbar puncture (LP). As part of an extensive biochemical migraine research program, we assessed the occurrence, duration, and characteristics of PDPH in 160 migraineurs and 53 age- and sex-matched healthy controls. In addition, we evaluated potential risk factors for PDPH as well as the risk of developing a migraine attack before or after LP. In total, 64 of 199 subjects (32.2%) developed PDPH. Young age, low body mass index, severe headache immediately after LP, and sitting sampling position, but not being a migraineur, increased the risk of PDPH (all p < 0.05). Duration of PDPH was prolonged by history of depression, sitting sampling position, high perceived stress during the LP procedure, and multiple LP efforts (all p < 0.05). Migraine attacks were less likely to occur before or shortly after LP. Migraineurs are not at increased risk of developing PDPH. PDPH duration is similar in migraineurs and age- and sex-matched controls. LP does not trigger migraine attacks, and the stress of an upcoming LP might even have a protective effect against onset of migraine attacks.