Acute Migraine Treatment in Adults

There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office‐based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti‐inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID–triptan combinations, dihydroergotamine, non‐opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti‐emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence‐based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication overuse is eliminated or avoided. Migraine treatment is complex, and treatment must be individualized and tailored to the patient's clinical features. Clinicians should make full use of available medications and formulations in an organized approach.     

Management of Pediatric Migraine Headache in the Emergency Room and Infusion Center

Migraine is a common disorder that starts at an early age and takes a variable pattern from intermittent to chronic headache with several exacerbations throughout a lifetime. Children and adolescents are significantly affected. If an acute headache is not aborted by outpatient migraine therapy, it often causes severe disability, preventing the child from attending school and social events. Treating the acute severe headache aggressively helps prevent prolonged disability as well as possible chronification. Multiple medications are available, mostly for the outpatient management of an attack and include the use of over‐the‐counter anti‐inflammatory medications as well as prescribed medications in the triptan group. These therapies do sometime fail and the exacerbation can last from days to weeks. If the headache lasts 72 hours or longer it will fall in the category of status migrainosus. Status migrainosus is described as a severe disabling headache lasting 72 hours or more by the ICHD3 criteria. Disability is a major issue in children and adolescents and aggressive acute measures are to be taken to control it as soon as possible. Early aggressive intravenous therapy can be very effective in breaking the attack and allowing the child to be quickly back to normal functioning. This article reviews what is available for the treatment of pediatric primary headaches in the emergency room.     

Botulinum toxins in the treatment of migraine and tension-type headaches

Botulinum toxins are promising preventive treatments for patients with moderate to severe episodic and chronic migraine and chronic daily headache. The recommended indications for botulinum toxins as preventive therapy lend themselves to the following patient types: those who demonstrate a lack of improvement from preventive (prophylactic) pharmacotherapy; those who experience severe and intolerable adverse events from preventive medications; those who refuse to use daily medications; those who have contraindications to acute migraine therapy, and elderly patients with chronic migraine. Both open-label and double-blind placebo-controlled studies using fixed-site, "follow the pain." or a combination approach have demonstrated significant reduction in migraine frequency, severity, and duration, as well as decreased use of acute medications. The most prominent reductions have been noted in those with reportedly the most severe migraine headaches. Large, well-designed, double-blind, placebo-controlled studies are recommended to further clarify optimum dosage and location of injection, reduce treatment frequency and duration, and address other primary headache disorders that may benefit from this therapy.     

Utility of topiramate for the treatment of patients with chronic migraine in the presence or absence of acute medication overuse

Chronic migraine has been linked to the excessive use of acute headache medications. Medication overuse (MO) is commonly considered the most significant risk factor for the progression of migraine from an episodic to a chronic condition. Managing MO is a challenge. Discontinuation of the acute medication can result in withdrawal headache, nausea, vomiting and sleep disturbances. This review summarizes the results from two similarly designed, randomized, placebo-controlled, multicentre studies of chronic migraine conducted in the USA and European Union. Both studies demonstrate the efficacy and safety of the migraine preventive medication, topiramate, for the treatment of chronic migraine in patient populations both with and without MO. These studies may have important implications for the future of chronic migraine management, suggesting that detoxification prior to initiating prophylactic therapy may not be required in all patients if MO is present.     

Oral transmucosal fentanyl citrate for the treatment of migraine headache pain in outpatients: a case series

BACKGROUND: Migraine headache pain that does not respond to traditional antimigraine medications frequently requires treatment in the emergency department (ED) with parenteral opioids. Rapid onset of pain relief in an outpatient setting for migraine headache is the primary objective of patients and clinicians. Oral transmucosal fentanyl citrate (OTFC; ACTIQ) is a novel opioid product designed to deliver rapid analgesia to patients who experience breakthrough pain (BTP). OBJECTIVE: To evaluate the effectiveness, tolerability, and patient satisfaction with OTFC for the outpatient treatment of acute, refractory migraine headache pain. PATIENTS AND METHODS: Twenty patients with recurrent acute, refractory migraine headaches who had been referred to this headache clinic are reported in this case series. All patients had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. Patients were prescribed OTFC (400 microg) as rescue treatment for moderate or severe migraine headache pain as outpatients. Patients were instructed to self-administer OTFC at home and complete a diary recording: pain intensity (11-point scale; 10 = worst pain imaginable to 0 = no pain) before and 15, 30, 60, and 120 minutes after OTFC; satisfaction with the effectiveness of OTFC (selecting 1 of 7 categories ranging from "very dissatisfied" through "very satisfied") rated at 120 minutes; and adverse events. RESULTS: Eighteen patients (13 female) experienced a migraine and self-administered OTFC. OTFC successfully treated migraine episodes in all 18 outpatients; no patient went to an ED. OTFC rapidly reduced pain intensity, with significant improvement at 15 minutes that was sustained and provided progressively more pain relief at 30, 60, and 120 minutes (all P <.01). Mean (SEM) pain intensity significantly declined from 8.83 (0.35) pretreatment to 2.28 (0.67) at 120 minutes, an average reduction of 75% (P <.01). Patients' satisfaction ratings with OTFC were overwhelmingly positive, with 94% being satisfied and more than half (56%) being "very satisfied." Three (17%) patients experienced nausea, two (11%) somnolence, and one (6%) each itching, vomiting, and dry mouth. All adverse events were mild or moderate in severity. CONCLUSIONS: OTFC rapidly and significantly relieved acute, refractory migraine pain in outpatients, prevented the need for an ED visit, and was associated with high patient satisfaction ratings. The rapid onset of migraine headache pain relief in this case series is consistent with the analgesic effect reported with the use of OTFC in patients with BTP. OTFC was well tolerated in these patients who had a history of tolerating parenteral opioids in the ED when experiencing refractory migraine pain and had been treated with outpatient opioid therapies in attempts to manage their migraine pain. OTFC may be effective for outpatient treatment of acute, refractory migraine headache pain. Further controlled studies are warranted.     

Establishing principles for migraine management in primary care

Published guidelines for the management of migraine in primary care were evaluated by an international advisory board of headache specialists, to establish evidence-based principles of migraine management that could be recommended for international use. Twelve principles of migraine management were identified, covering screening, diagnosis, management and treatments: Almost all headaches are benign/primary and can be managed by all practising clinicians. Use questions/a questionnaire to assess the impact on daily living and everyday activities, for diagnostic screening and to aid management decisions. Share migraine management between the clinician and the patient. Provide individualised care for migraine and encourage patients to manage their migraine. Follow up patients, preferably with migraine calendars or diaries. Regularly re-evaluate the success of therapy using specific outcome measures and monitor the use of acute and prophylactic medications regularly. Adapt migraine management to changes that occur in the illness and its presentation over the years. Provide acute medication to all migraine patients and recommend it is taken at the appropriate time, during the attack. Provide rescue medication/symptomatic treatment for when the initial therapy fails. Offer to prescribe prophylactic medications, as well as lifestyle changes, to patients who have four or more migraine attacks per month or who are resistant to acute medications. Consider concurrent co-morbidities in the choice of appropriate prophylactic medication. Work with the patient to achieve comfort with mutually agreed upon treatment and ensure that it is practical for their lifestyle and headache presentation. Using these principles, practising clinicians can screen and diagnose their headache patients effectively and manage their migraine patients over the long-term natural history of the migraine process. In this way, the majority of migraine patients can be well treated in primary care, ensuring a structured and individualised approach to headache management, and conserving valuable healthcare resources.     

Medication overuse headache

Medication overuse headache may complicate any type of headache and occurs in young people, adults, and even elderly patients.Overuse of acute medications may change intermittent or self-limited headaches into chronic daily headache. Migraineurs seem particularly prone to analgesic rebound headache/ transformed migraine/chronic migraine. Prophylactic therapies are often ineffective in the setting of medication overuse. Recognition of this condition allows appropriate clinical intervention that includes cessation of the offending medications.     

Providing Care for Patients with Chronic Migraine: Diagnosis,Treatment, and Management

Chronic migraine, a subtype of migraine defined as ≥ 15 headache days per month for ≥ 3 months, in which ≥ 8 days per month meet criteria for migraine with or without aura or respond to migraine‐specific treatment, is a disabling, underdiagnosed, and undertreated disorder associated with significant disability, poor health‐related quality of life, and high economic burden. The keys to caring for chronic migraine patients include: (1) making a proper diagnosis; (2) identifying and eliminating exacerbating factors; (3) assessing for medication overuse (patients with chronic headache often overuse acute medications); and (4) continued management. Communication between patient and physician about treatment goals is important. The patient management guidelines presented in this article should help physicians improve treatment success and proactively address common comorbidities among their patients with chronic migraine.     

Neuromodulators for migraine prevention

Migraine is a debilitating condition characterized by a cycle of painful headaches and headache-related symptoms interspersed with periods of worry, distress, and apprehension. The negative impact of migraine on patient functioning, workplace productivity, and other daily activities has been demonstrated through the use of a variety of clinician- and patient-reported assessment tools, including the Migraine-Specific Questionnaire and the Migraine Disability Assessment questionnaire. In addition to considering the frequency and severity of migraine, clinicians need to encourage more open dialogue with their patients about the impact of this disorder on daily activities and productivity. Only then can the most appropriate course of treatment be determined. Appropriately prescribed acute and preventive therapies should break the cycle of migraine and improve the daily activities of patients with this chronic condition. Divalproex sodium and topiramate are neuromodulators that are approved by the US Food and Drug Administration (FDA) for the prophylaxis (prevention) of migraine headache in adults. Non-FDA-approved neuromodulators sometimes used in the management of migraine headache include gabapentin, lamotrigine, levetiracetam, and zonisamide. All medications need to be titrated, and treatment-related adverse events need to be managed appropriately. Preventive medications should be taken for at least 2-3 months to ascertain their therapeutic effect.     

Managing chronic headaches in the clinic

Chronic daily headache (CDH), which is often linked to a history of migraine, tension-type headache and the abuse of headache medications, and cluster headache are the best known of the chronic headaches. These headaches may not be well recognised or well treated in primary care. This article outlines the development of management algorithms for these headache subtypes, designed for use by the primary care physician with an interest in headache. Principles of care for chronic headaches include implementation of screening procedures, differential diagnosis, tailoring of management to the individual's needs, proactive follow-up and a team approach to care. These principles can be customised to the headache subtype by the selection of appropriate therapies. The optimal treatments for CDH include physical therapy to the neck if there is any stiffness there, withdrawal of abused medications and treatment of any subsequent withdrawal symptoms and headache prophylaxis, together with the provision of acute medications as rescue therapy. Optimal treatments for cluster headache include short- and long-term prophylaxis to prevent the headaches developing and acute medications for use as rescue. If treatment is ineffective, alternative medications can be provided at follow-up, with the possibility of referral for refractory patients.     

Practice and Economics Cost Considerations in Headache Treatment Part 2: Acute Migraine Treatment

Today's physician has many useful medication options available for acute migraine treatment. There is a wide cost range among these drugs and today's health care environment demands that cost be factored into the decision process. Effective migraine abortive treatment decreases the costs of repeat dosing and disability. Early use of migraine abortive medication can increase its rapidity of action and effectiveness. Adjunctive medication such as metoclopramide ($0.10) is inexpensive and may improve the effectiveness of the primary abortive medication.
Over-the-counter medications such as aspirin ($0.02/325 mg), Excadrin· ($0.09/tablet), ibuprofen ($0.04/200 mg), or naproxen sodium ($0.09/220 mg) are inexpensive and effective. "Triple therapy" combining metoclopramide, a nonsteroidal ant-inflammatory agent, and an ergotamine preparation may improve tolerance and effectiveness of the ergot. Locally compounded dihydroergotamine nasal spray is inexpensive ($0.78/1 mg spray). The cost of using oral sumatriptan can be almost halved by prescribing half of a 50-mg tablet.
Emergency department services are expensive. Huge cost savings occur through self-controlled administration of oral, rectal, or even intramuscular narcotic medications. Oral narcotic agents such as hydromorphone ($0.42/4 mg) and meperidine ($0.92/200 mg) are generally used in inadequate doses to be effective for severe migraine. Guidelines are given for more effective use of these agents.
Sophisticated comparative studies are needed to evaluate, not only the direct costs of medications, but all costs of treatment of an acute migraine attack, as well as Indirect costs to the patient, family, and society.     

Prophylaxis for chronic daily headache and chronic migraine with neuronal stabilizing agents

Approaches to acute and prophylactic migraine and headache treatment are evolving as our understanding of some of the underlying pathophysiology improves. This article focuses on the emerging use of medications originally introduced for the treatment of seizures (anticonvulsants) as primary therapy for eradicating or reducing migraine and chronic daily headaches. A more accurate term for their pharmacologic mechanisms, if they are used to treat headaches and pain disorders, is neuromodulating or neuronal stabilizing agents. This term refers to their many cellular actions to reduce pain transmission supraspinally, in the spinal cord, and in the brainstem.     

Opioid Treatment of Migraine: Risk Factors and Behavioral Issues

Migraine can impact every aspect of a person’s functioning. Psychological comorbidities, cognitive constructs, and behavioral responses to pain greatly impact the perception of migraine pain, treatment efficacy and outcome, and overall quality of life and functioning. Current considerations for migraine treatment emphasize the utility of the biopsychosocial model in understanding and treating migraine, noting both the importance of addressing psychological factors such as cognitive beliefs as well as psychiatric comorbidities. The guidelines for migraine treatment implicate opioid therapy as a second or third tier treatment. Guidelines and recommendations for the safe use of opioid medications among patients with chronic pain emphasize the importance of screening prior to prescribing opioid medications. Chronic opioid therapy has been shown to further levels of disability, decrease quality of life, and correlate to psychiatric comorbidities, concerns that are already present in migraine patients. While opioid treatment provides an alternative for persons with contraindications for alternative migraine treatments, it is critical that opioids be used sparingly and exclusively in conjunction with comprehensive assessment and integration of psychological treatment.     

The medical management of migraine

Migraine is a common, chronic neurologic disorder that affects 11% of the adult population in Western countries. In this article, we review the current approaches to the pharmacologic treatment of migraine. Once migraine is diagnosed, and illness severity has been assessed, clinicians and patients should work together to develop a treatment plan based on the patient needs and preferences. The goals of the treatment plan usually include reducing attack frequency, intensity, and duration; minimizing headache-related disability; improving health-related quality of life; and avoiding headache escalation and medication misuse. Medical treatments for migraine can be divided into preventive drugs, which are taken on a daily basis regardless of whether headache is present, and acute drugs taken to treat individual attacks as they arise. Acute treatments are further divided into nonspecific and migraine-specific treatments. The US Headache Consortium Guidelines recommend stratified care based on the level of disability to help physicians individualize treatment. Simple analgesics are appropriate as first-line acute treatments for less disabled patients; if simple analgesics are unsuccessful, treatment is escalated. For those with high disability levels, migraine-specific acute therapies, such as the triptans, are recommended as the initial treatment, with preventive drugs in selected patients. A variety of behavioral interventions are helpful. The clinicians have in their armamentariums an ever-expanding variety of medications. With experience, clinicians can match individual patient needs with the specific characteristics of a drug to optimize therapeutic benefit.     

Chronic Migraine With Apparent Loss of Response to Onabotulinum Toxin Type A Due to Local Nitroglycerin Treatment for an Anal Fissure: A Case Report

Many patients with chronic migraine are difficult to treat. We present a patient with chronic migraine with good response to onabotulinum toxin type A whose headaches worsened in clear temporal relationship to local treatment with glyceryl trinitrate for an anal fissure. Our case shows that the use, even at distance, of nitric oxide donors can be a precipitating factor for migraineurs and should be always inquired in chronic migraine patients. In addition, the presence of frequent headaches should always be ruled out before prescribing such medications.     

Renal papillary necrosis following emergency department treatment of migraine

New medications have lessened the need for narcotic medications in the acute treatment of migraine. Some of these new medications include parenteral dihydroergotamine (DHE), sumatriptan, and ketorolac. Treatment failures still occur, though, and some cases necessitate adding a second agent to one that has been ineffective. We report a case of a 46-year-old man who suffered renal papillary necrosis 12 days after receiving parenteral DHE, sumatriptan, and ketorolac for treatment of a severe migraine headache. There were no signs of an adverse drug reaction at the time of his emergency department visit. The case illustrates a potential hazard of this combination in the acute treatment of migraine.     

Screening and behavioral management: obesity and weight management

Individuals with migraine headaches who are obese or overweight may be at elevated risk for experiencing more frequent migraines and for developing chronic migraine. This makes it imperative that clinicians consider including weight management as part of a migraine treatment plan in situations where the patient is overweight or obese. Weight loss and weight maintenance therapy should employ a combination of behavioral strategies, in particular nutritional education, dietary intervention, and exercise counseling, as a first line intervention. Weight loss medications are considered a secondary treatment; however, when weight loss medications are used, it is vital to monitor the influence of the medication on headache. Similarly, a clinician considering migraine prophylaxis needs to consider whether the pharmacologic agent being considered influences weight gain or loss.     

Pharmacological synergy: the next frontier on therapeutic advancement for migraine

The burden of migraine significantly impacts the individual sufferer, their families, the workplace, and society. The World Health Organization has identified migraine as an urgent public health priority and has initiated a global initiative to reduce the burden of migraine. Underlying the World Health Organization initiative is the need to discover means of optimizing migraine treatments and make them accessible to the broader portion of the world population. Development of acute migraine medications over the past several decades has largely centered on engineering highly specific receptor molecules that alter migraine pathophysiological mechanisms to abort or reverse the acute attack of migraine. The first product of this line of discovery was sumatriptan and heralded as a landmark therapeutic breakthrough. Sumatriptan is a 5-HT-1B/D receptor agonist considered to activate receptors involved in the pathophysiology specific to migraine. Large-scale regulatory/clinical studies demonstrated statistical superiority for sumatriptan over placebo in reduction or elimination of headache, nausea, photophobia, and phonophobia. Since the introduction of sumatriptan, 6 other triptan products have been released in the United States as acute treatments for migraine, all having the same mechanism of action and similar efficacy. Despite their utility as migraine abortive medications, the triptans do not successfully treat all attacks of migraine or necessarily treat all migraine associated symptoms. In fact, in less than 25% of attacks do subjects obtain and maintain a migraine-free response to treatment for at least beyond 24 hours. A wide range of non-triptan medications also have demonstrated efficacy in acute migraine. These include non-steroidal anti-inflammatory drugs (NSAIDs), opioids, phenothiazines, and valproic acid to name a few. Given the distinctly different mechanisms of actions of these various medications, it is likely that several unique pathophysiological mechanisms are involved in terminating acute episodes of migraine. Clinicians now capitalize on this observation and use migraine medication in combination with another to improve patient outcomes, for example, using an antiemetic with an opioid or a triptan and NSAIDs. More recently, the Food and Drug Adminstration has approved a combination product containing 85mg of sumatriptan plus 500mg of naproxen sodium for acute treatment of migraine. Clinical trials conducted prior to approval demonstrated that the combination of sumatriptan and naproxen was more effective as a migraine abortive than either of its components but that each component and the combination were more effective than placebo. Exactly how sumatriptan and naproxen interact to create therapeutic synergism is unknown though its mere occurrence suggests that models assisting medical understanding and prediction of pharmacological synergism may improve clinical outcome over products acting through a single receptor mechanism. Migraine is a syndrome, meaning it is defined by observed symptoms rather than known pathophysiology. Multiple pathogenic mechanisms are likely involved in generating this diverse array of symptoms understood as the migraine symptom complex. Sumatriptan and naproxen have independent mechanisms of action and target distinct aspects of the vascular and inflammatory processes hypothesized to underlie migraine. Sumatriptan acts on the 5-HT(1B) and 5-HT(1D) receptors, whereas naproxen inhibits the COX-1 and COX-2 enzymes. Sumatriptan has vasoconstricting effects as well as effects on neurogenic inflammation by decreasing the release of substance P and calcitonin gene-related peptide. In contrast, naproxen affects prostaglandins and other inflammatory mediators. Because sumatriptan and naproxen both relieve migraine yet interact with different cellular targets within the migraine pathway, it is reasonable to assume there is a unique synergy between these medications that improves treatment outcomes. Clinical trials supported this contention by demonstrating the combination of sumatriptan/naproxen alleviated migraine pain quickly (primarily based on the sumatriptan mechanism of action), and sustained the response longer (primarily based on the naproxen mechanism of action) than is possible when either drug is given alone. The working hypothesis is that when sumatriptan and naproxen are given at the same time, they affect different mechanisms of the migraine pathway and produce an enhanced therapeutic effect. The purpose of this article is to apply statistical analyses to data from phase II and phase III studies of the combination of sumatriptan and naproxen to determine if this enhanced therapeutic effect is synergistic. This methodology of accessing synergy can be used in the development of future combination migraine treatments to improve treatment outcomes.