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1.  Preventing chronicity of migraine 
The Journal of Headache and Pain  2005;6(4):331-333.
Chronic migraine and transformed migraine are conditions with a progression from episodic to chronic headache, a disabling stage. During attack, cutaneous allodynia frequently occurs: it reflects sensitisation of the central neurons of the trigeminovascular system. Early triptan therapy (prior to the development of central sensitisation) may protect from the chronicisation of migraine. In addition, early recognition of non–headache changes in neurologic function between episodes of headache offers a sensitive indicator of headache transformation. Attack frequency is the stronger predictor for migraine progression: prophylactic agents could be administered to patients with a high number of attacks. Medication overuse is the most important iatrogenic risk factor for the acceleration of disease and it must be prevented; other important risk factors are female sex, obesity and stressful life events.
PMCID: PMC3452012  PMID: 16362703
Chronic migraine; Central sensitisation; Disease progression; Risk factor; Medication overuse
2.  Menstrual migraine 
The Journal of Headache and Pain  2001;2(Suppl 1):s117-s119.
An association between migraine and menstruation can be ascertained by use of a diary for a minimum of three cycles. The pathophysiological and clinical peculiarities of menstrual migraine indicate that its management should differ from that of non–menstrual migraine. NSAIDS or migraine-specific medications (e.g. triptans) are often effective for the acute management of menstrual migraine. Preventive treatment is indicated when the attacks are long–lasting, severe and disabling and do not respond to acute treatments. Short–term prophylaxis (at the time of headache vulnerability) employs standard drugs such as magnesium, ergotamine or NSAIDs; triptans are currently being evaluated for short–term prophylaxis. If severe menstrual migraine attacks cannot be controlled by these, hormone therapy (percutaneous or transdermal estrogen) may be indicated. Antiestrogen agents (danazol, tamoxifen) are indicated only in rare resistant cases.
PMCID: PMC3451824
Menstruation; Migraine; Therapy; Sex hormones
3.  Recent advances in the pharmacological management of migraine 
Pharmacological treatment of migraine includes acute and, in some patients, preventive medications. Here, the most relevant recent advances in migraine management are reviewed. Regarding acute treatment, new data indicate that early treatment of migraine attacks should be recommended to those patients who do not show a clear response when pain is already moderate or severe. It has also been shown that, in terms of efficacy, the combination of a nonsteroidal anti-inflammatory drug plus a triptan is superior to monotherapy. In the immediate future it seems that a new class, the antagonists of calcitonin gene-related peptide, will offer at least the same efficacy as that of potent triptans, but a much better tolerability and no vascular contraindications. Concerning migraine prevention, news has been concentrated on the management of chronic migraine, with the appearance of guidelines for clinical trials in chronic migraine and the demonstration that it is a treatable entity, even in the presence of overuse criteria.
PMCID: PMC2924709  PMID: 20948742
4.  Acute treatment of headache 
The Journal of Headache and Pain  2006;7(5):355-359.
Effective acute treatment of headache begins with making an accurate diagnosis and ruling out secondary causes of headache. Once a primary headache is diagnosed, it is important to choose the right combination of behavioural therapy and acute care (abortive and symptomatic) therapy for each patient. Some patients may need preventive medication on a daily basis. If patients overuse acute medications and develop medication overuse headache (previously called analgesic rebound headache), they often seek medical attention due to the chronicity and/or intensity of their pain and resultant disability. For acute care of migraine, physicians should choose a triptan they know and expect to work. They should prescribe the dose and route of administration that will provide the most rapid and complete response to all the associated symptoms of migraine, in addition to the pain. The effectiveness of the 7 available triptans in early, double-blind, controlled trials is more similar than different. How and when to give them will be discussed. Treatment of cluster headache will be presented briefly.
PMCID: PMC3468178  PMID: 17058043
Headache; Treatment; Acute care
5.  Update on Medication-overuse Headache 
Medication-overuse headache (MOH) is a syndrome that can develop in migraineurs after overuse of antimigraine drugs, including opiates and triptans especially. MOH manifests as increased frequency and intensity of migraine attacks and enhanced sensitivity to stimuli that elicit migraine episodes. Although the mechanisms underlying MOH remain unknown, it is hypothesized that repeated use of antimigraine drugs could elicit increased headache attacks as a consequence of neuronal plasticity that may increase responsiveness to migraine triggers. Preclinical studies show that exposure to either opiates or triptans can induce pronociceptive neuroadaptive changes in the orofacial division of the trigeminal ganglia that persist even after discontinuation of the drug treatment. Additionally, medications can elicit increased descending facilitatory influences that may amplify evoked inputs from trigeminal afferents leading to behavioral hypersensitivity reminiscent of cutaneous allodynia observed clinically. Importantly, enhanced descending facilitation may manifest as an inhibition of diffuse noxious inhibitory control. Persistent, pronociceptive adaptations in nociceptors as well as within descending modulatory pathways thus may jointly contribute to the development of MOH.
PMCID: PMC3780979  PMID: 21058047
Migraine; Medication-overuse headache; Opiates; Triptans; Neuroadaptive changes
6.  Chronic migraine plus medication overuse headache: two entities or not? 
The Journal of Headache and Pain  2011;12(6):593-601.
Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.
PMCID: PMC3208042  PMID: 21938457
Chronic migraine; Refractory chronic migraine; Medication overuse headache; Detoxification; Rehabilitation; OnabotulinumtoxinA
7.  Chronic migraine plus medication overuse headache: two entities or not? 
The Journal of Headache and Pain  2011;12(6):593-601.
Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA.
PMCID: PMC3208042  PMID: 21938457
Chronic migraine; Refractory chronic migraine; Medication overuse headache; Detoxification; Rehabilitation; OnabotulinumtoxinA
8.  A review of the use of frovatriptan in the treatment of menstrually related migraine 
Menstrual migraine (MM) is a highly prevalent condition associated with considerable disability. Migraine attacks occur exclusively around the menstrual period in approximately 10% of women with migraine, that is, pure menstrual migraine, while at least 50% of them also experience migraine at other times of the month, that is, menstrually related migraine (MRM). The therapeutic approach to patients with MRM is based on treatment of the attack, or prophylactic strategies. Triptans are recommended as first-line treatments for moderate to severe migraine attacks, including MM. Frovatriptan is one of the newest triptans. Its high affinity for 5-HT1B/1D receptors and long half-life contribute to its distinctive clinical effect, characterized by a more sustained and prolonged effect than other triptans. Indeed, frovatriptan proved to be effective in treating the acute attack, but was particularly effective in the short-term preventive therapy of MM. In addition, frovatriptan is one of the safest triptans, with the lowest risk of treatment-emergent adverse events. Following extensive evidence from randomized pharmacological trials, frovatriptan has now gained a grade A recommendation from the guidelines for short-term prophylaxis of MM. Recent post-hoc analyses of direct comparative trials also suggest that frovatriptan might have an important role in the acute treatment of MRM. In these studies, frovatriptan showed pain relief and pain-free rates similar to those of zolmitriptan, rizatriptan, and almotriptan, but with significantly lower recurrence rates. More well-designed, randomized, prospective studies, specifically enrolling women with MM, will be needed in the near future to confirm the efficacy of frovatriptan in this migraine subtype.
PMCID: PMC3582308  PMID: 23483096
frovatriptan; menstrual migraine; menstrually related migraine
9.  Acute migraine: Current treatment and emerging therapies 
Migraine is a common disabling primary headache disorder. Despite the need for a perfect treatment of this debilitating condition, the ideal “cure” eludes us. In 1992, the first triptan was released in the US for use in acute migraine. Triptans are more specific for the serotonin receptor 5-hydroxy triptamine (5-HT) 1 than previously prescribed drugs, such as ergotamines, with fewer side effects. This was an important first step in specific acute migraine therapy. Today however, triptans continue to be underutilized. There remains a concern, among practitioners and patients, about possible cardiovascular safety issues, despite the lack of strong evidence of serious adverse events. In fact, triptans now have a safe track record over more than a decade of use. Other perceived downfalls to use, include cost and variable efficacy. The more we learn about the clinical features and pathophysiology of migraine, the closer we are to finding a satisfactory monotherapy. Until then, recognizing that mixed mechanisms underlie migraine symptoms, rational polytherapy can be useful. Research on the roles of serotonin, calcitonin gene related peptide, glutamine and N-methyl-D-aspartate in the trigeminovascular system holds promise for those searching for the perfect migraine headache cure.
PMCID: PMC2386351  PMID: 18488069
migraine; pathophysiology; acute; treatment
10.  Impact of a public sensitization campaign on migraine management in France 
The Journal of Headache and Pain  2009;10(4):241-247.
Migraine is a common and frequently disabling condition. Nevertheless, many migraine sufferers do not consult for migraine, are not medically followed up and self-treat the attacks. “Tour de France of migraine” consisted of free-access conferences held in six large towns in France following a wide public information campaign. This sensitization campaign aimed at providing participants with educational information on migraine disease and on current therapies. Headache sufferers were then invited to respond to two consecutive questionnaires delivered at the end of the conferences and 3 months later to assess the influence of the information delivered on their migraine management. Tour de France of migraine recruited mainly severe migraine sufferers, most of whom had already consulted and were medically followed up. However, migraine management was often suboptimal in these subjects since most of them found their acute treatment of attacks ineffective and only few of them received a prophylactic treatment. Three months after the conferences, more than half of respondents had consulted for headaches. There was a significant improvement in migraine-related disability, as reflected by a significant decrease in mean Headache Impact Test 6-item score, which might have been related to the higher proportion of subjects receiving a prophylactic treatment of migraine. The Tour de France of migraine campaign revealed the difficulty in sensitizing migraine sufferers towards the necessity of being medically followed up. Mainly patients with severe migraine attended the conferences and derived clinical benefit from the educational program. Other strategies should be developed to reach a wider population of migraine sufferers.
PMCID: PMC3451749  PMID: 19484351
Migraine; Medical follow-up; Burden of migraine; Patient education
11.  Acute treatment of migraine. Breaking the paradigm of monotherapy 
BMC Neurology  2004;4:4.
Migraine is a highly prevalent disorder. The disability provoked by its attacks results in suffering as well as considerable economic and social losses. The objective of migraine acute treatment is to restore the patient to normal function as quickly and consistently as possible. There are numerous drugs available for this purpose and despite recent advances in the understanding of the mechanisms and different biological systems involved in migraine attacks, with the development of specific 5-HT agonists known as triptans, current options for acute migraine still stand below the ideal.
Monotherapeutic approaches are the rule but up to one third of all patients discontinue their medications due to lack of efficacy, headache recurrence, cost and/or side effects. In addition, a rationale has been suggested for the development of polytherapeutic approaches, simultaneously aiming at some of the biological systems involved. This paper reviews the fundamentals for this changing approach as well as the evidence of its better efficacy.
As a conclusion, most of the patients with a past history of not responding (no pain-free at 2 hours and/or no sustained pain-free at 24 hours) in at least 5 previous attacks should undergo a combination therapy suiting to their individual profile, which must include analgesics or non-steroidal anti-inflammatory agents plus a triptan or a gastro kinetic drug. The three-drug regimen may also be considered. In addition, changing the right moment to take it and the choice for formulations other than oral has also to be determined individually and clearly posted to the patient.
PMCID: PMC341456  PMID: 15005810
migraine; acute treatment; polytherapy; changing approach
12.  Optimal management of severe nausea and vomiting in migraine: improving patient outcomes 
Migraine is a common and potentially disabling disorder for patients, with wide-reaching implications for health care services, society, and the economy. Nausea and vomiting during migraine attacks are common symptoms that affect at least 60% of patients suffering from migraines. These symptoms are often more disabling than the headache itself, causing a great burden on the patient’s life. Nausea and vomiting may delay the use of oral abortive medication or interfere with oral drug absorption. Therefore, they can hinder significantly the management and treatment of migraine (which is usually given orally). The main treatment of pain-associated symptoms of migraine (such as nausea and vomiting) is to stop the migraine attack itself as soon as possible, with the effective drugs at the effective doses, seeking if necessary alternative routes of administration. In some cases, intravenous antiemetic drugs are able to relieve a migraine attack and associated symptoms like nausea and vomiting. We performed an exhaustive PubMed search of the English literature to find studies about management of migraine and its associated symptoms. Search terms were migraine, nausea, and vomiting. We did not limit our search to a specific time period. We focused on clinical efficacy and tolerance of the various drugs and procedures based on data from human studies. We included the best available studies for each discussed drug or procedure. These ranged from randomized controlled trials for some treatments to small case series for others. Recently updated books and manuals on neurology and headache were also consulted. We herein review the efficacy of the different approaches in order to manage nausea and vomiting for migraine patents.
PMCID: PMC3798203  PMID: 24143125
migraine; nausea; vomiting; management; treatment
13.  The use of combination therapies in the acute management of migraine 
Background and objectives
Migraine is a highly prevalent neurological disorder with multiple peripheral and central mechanisms. Targeting a single mechanism for treating individual attacks as well as for performing the prophylaxis has been shown to be only partially effective. Recently, the role of combining agents for acute migraine treatment has gained attention and the combination of a triptan plus a non-steroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This review focuses on the fundamentals of treating migraine attacks with two or more agents, and emphasizes the characteristics of the recently approved fixed combination sumatriptan–naproxen.
A PubMed search using the terms “migraine”, “treatment”, “acute”, “triptans”, “non-steroidal anti-inflammatory drugs”, “sumatriptan”, “naproxen”, and “combination” was used. In addition, abstracts presented in the major meetings of the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated.
Although most of the few studies encountered were not controlled, there is a clear trend for better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50 mg and 85 mg) with 500 mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the use of each agent alone. The differences in the endpoints 24-hour pain-relief response as well as pain-free and pain-relief parameters at 2-hour time-point are the most noticeable efficacy measures. Tolerability was not different between studied drugs.
Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over monotherapy with each one these options. Recently issued FDA approval for marketing the combination (sumatriptan 50 mg–naproxen 500 mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.
PMCID: PMC2671814  PMID: 19412476
migraine; acute treatment; sumatriptan; naproxen; combination
14.  Strategies of care for acute treatment of migraine 
The clinical questions posed by the advent of acute migraine-specific treatment (triptans) are on which patient to use specific treatment for migraine, and when in the attack to treat patients. Three strategies have been proposed for selecting treatment for acute migraine, and these strategies were studied in The Disability in Strategies of Care (DISC) study: step care across attacks, step care within attacks, and stratified care. Stratified care, which matches treatment to level of disability is superior to the other two strategies. A recent prospective study suggests that triptans should be used during the mild phase of pain for optimal benefit. Thus, patients with time loss from episodic migraine are optimal candidates for triptan therapy from the beginning, and treating early in attacks, without delay, optimizes the likelihood of pain relief and reducing that time loss and disability.
PMCID: PMC3613230
Key words Migraine; Disability; Stratified care; Step care; Triptans
15.  Preventive treatment in migraine and the new US guidelines 
Migraine headaches are among the most common headache disorders seen in various practices. The prevalence of migraine headaches is 18% in women and 6% in men. While millions of Americans suffer from migraine headaches, roughly 3%–13% of identified migraine patients are on preventive therapy, while an estimated 38% actually need a preventive agent. The challenge among physicians is not only when to start a daily preventive agent but which preventive agent to choose. Circumstances warranting prevention have been described in the past, and in 2012, a new set of guidelines with an evidence review on preventive medications was published. A second set of guidelines provided evidence on nonsteroidal anti-inflammatory drugs, herbs, minerals, and vitamins for prevention of episodic migraine. This article describes the updated US guidelines for the prevention of migraines and also outlines the major studies from which these guidelines were derived.
PMCID: PMC3663475  PMID: 23717045
US guidelines; Canadian guidelines; classification; preventive medication
16.  Topiramate in the prevention and treatment of migraine: efficacy, safety and patient preference 
Migraine is a very common disorder characterized by the combination of typical headache with associated autonomic symptoms and/or the presence of aura. Considerable advances have been made in recent years to understand the pathophysiology of migraine, which has led to improved treatment options for the acute migraine attack as well as migraine prophylaxis. Unfortunately, preventive treatment is often insufficient to decrease migraine frequency substantially or is not well tolerated. Topiramate is an antipileptic drug with a complex mode of action which has proven its efficacy and safety in the prophylactic treatment of episodic migraine in a number of randomized controlled clinical trials. Topiramate is also effective in treating patients with chronic migraine. It has little pharmacological interaction with other drugs and is generally well tolerated by patients.
PMCID: PMC2951059  PMID: 20169042
migraine; antiepileptic drugs; topiramate
17.  Migraine management: How do the adult and paediatric migraines differ? 
Migraine is one of the common causes of severe and recurring headache. It may be difficult to manage in primary care settings, where it is under diagnosed and medically treated. Migraine can occur in children as well as in adults and it is three times more common in women than in men. Migraine in children is different from adults in various ways. Migraine management depends on the various factors like duration and severity of pain, associated symptoms, degree of disability, and initial response to treatment. The therapy of children and adolescents with migraines includes treatment modalities for acute attacks, prophylactic medications when the attacks are frequent, and biobehavioural modes of treatment to aid long-term management of the disorder. The long lasting outcome of childhood headaches and progression into adult headaches remains largely unknown. However, it has been suggested that adult migraine may represent a progressive disorder. In children, the progressive nature is uncertain and further investigations into longitudinal outcome and phenotypic changes in childhood headaches have yet to be recognized. Even though paediatric and adult migraines seem to be slightly different from one another, but not enough to categorize either as sole.
PMCID: PMC3745030  PMID: 23960771
Adult; Headache; Migraine; Paediatrics
18.  Prophylaxis of migraine: general principles and patient acceptance 
Migraine is a chronic neurological condition with episodic exacerbations. Migraine is highly prevalent, and associated with significant pain, disability, and diminished quality of life. Migraine management is an important health care issue. Migraine management includes avoidance of trigger factors, lifestyle modifications, non-pharmacological therapies, and medications. Pharmacological treatment is traditionally divided into acute or symptomatic treatment, and preventive treatment or prophylaxis. Many migraine patients can be treated using only acute treatment. Patients with severe and/or frequent migraines require long-term preventive therapy. Prophylaxis requires daily administration of anti-migraine compounds with potential adverse events or contraindications, and may also interfere with other concurrent conditions and treatments. These problems may induce patients to reject the idea of a preventive treatment, leading to poor patient adherence. This paper reviews the main factors influencing patient acceptance of anti-migraine prophylaxis, providing practical suggestions to enhance patient willingness to accept pharmacological anti-migraine preventive therapy. We also provide information about the main clinical characteristics of migraine, and their negative consequences. The circumstances warranting prophylaxis in migraine patients as well as the main characteristics of the compounds currently used in migraine prophylaxis will also be briefly discussed, focusing on those aspects which can enhance patient acceptance and adherence.
PMCID: PMC2646645  PMID: 19337456
migraine; prophylaxis; preventive therapy; acceptance; adherence
19.  Comparison of the effects of dietary factors in the management and prophylaxis of migraine 
Journal of pain research  2010;3:125-130.
Migraine is defined as a disorder characterized by intermittent headache episodes, accompanied with nausea, photophobia and/or phonophobia. Pharmacological therapy is in accordance with the severity of pain and may include acute, prophylactic and most commonly both approaches. The aim of the acute therapy is stopping or alleviating the attack or progression of the pain and, in case of a migraine attack that has started, lessening the pain. Preventive therapy aims to reduce attack frequency and severity. This study was designed to evaluate the effect of dietary factors in the management and prophylaxis of migraine in cases diagnosed as having migraine disorder according to the 2003-IHS criteria. Fifty consecutive Turkish patients (13 men, 37 women) with diagnosis of migraine were randomly divided into two groups for treatment protocols with the written approval of the ethics committee. The cases in the first group (K) were treated with metoprolol, vitamin B2 (riboflavin), and naproxen sodium just at the aura or at the beginning of the attacks. The cases in the second group (D) were also supplied with a comprehensive dietary list arranged by our algology clinic in addition to the same medication protocol. There were no demographic differences between the cases (P > 0.05). VAS scores were lower in group D than group K (P < 0.01), and also the migraine attack frequencies and monthly amounts of analgesic consumed amounts were also statistically significantly less. It was concluded that beta-blocker and riboflavin therapy supplemented with a convenient diet with appropriate alternatives in patients with migraine disorder was associated with statistically significant decreases in headache frequency, intensity, duration and medication intake.
PMCID: PMC3004646  PMID: 21197315
migraine; food intake; trigger
20.  Triptans in prevention of menstrual migraine: a systematic review with meta-analysis 
Randomized clinical trials (RCT) assessing the efficacy and tolerability of triptans compared with placebo as short-term prophylaxis of menstrual migraine (MM) were systematically reviewed in this study. Triptans, which interfere with the pathogenesis of migraine and are effective in relieving associated neurovegetative symptoms, have been extensively proposed for prevention of menstrual migraine attacks. We searched Cochrane CENTRAL, MEDLINE and EMBASE for randomized, double-blind, placebo-controlled trials on triptans for MM until 1 Oct, 2012. A total of six RCTs were identified. Two authors independently assessed trial’s quality and extracted data. Numbers of participants free from MM per perimenstrual period (PMP), requiring rescue medication, suffering from headache-associated symptoms and experiencing adverse events in treatment and control groups were used to calculate relative risk (RR) and number needed to treat (NNT) with their corresponding 95% confidence interval (CI). A total of 633 participants received frovatriptan 2.5 mg QD, 584 received frovatriptan 2.5 mg BID, 392 received naratriptan 1 mg BID, 70 received naratriptan 2.5 mg BID, 80 received zolmitriptan 2.5 mg BID, 83 received zolmitriptan 2.5 mg TID and 1104 received placebo. Overall, triptans is an effective, short-term, prophylactic treatment of choice for MM. Considering MM frequency, severity and adverse events, frovatriptan 2.5 mg BID and zolmitriptan 2.5 mg TID tend to be the preferred regimens.
PMCID: PMC3620011  PMID: 23565873
Meta-analysis; Systematic review; Frovatriptan; Naratriptan; Zolmitriptan; Menstruation; Migraine; Prophylaxis
21.  Pharmacological treatment of attacks in juvenile migraine 
The Journal of Headache and Pain  2004;5(Suppl 2):s62-s66.
Although migraine is a common complaint in childhood and adolescence, there is a lack of controlled clinical studies regarding treatment. In the young patient, the pharmacological approach should be preceded by setting up non-pharmacological measures which include behavioural intervention. The sole use of symptomatic therapies should be limited to patients who complain of up to four partially or totally disabling attacks, or those who suffer from headache for more than 4 days per month. The therapeutic armamentarium includes non-specific symptomatic drugs, such as analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), as well as anti-emetics and specific drugs, such as the triptans. Analgesics and NSAIDs are the most frequently used drugs in childhood and adolescence for the symptomatic treatment of migraine attacks of slight or moderate intensity. The first-choice drug for those under 12 years of age is acetaminophen. Among NSAIDs, two double-blind, randomized, placebo-controlled studies were conducted for ibuprofen, supporting its efficacy. In the past, ergot derivatives played an important role in the treatment of spontaneous migraine attacks, particularly in adults, but after the triptan revolution their role was strongly confined to a small number of patients. Although they are considered first-choice drugs for moderate and severe migraine attacks in adults, triptans are still under study in migraine patients under 18 years of age. The Health Ministry rules do not approve their use in patients under 18 years. They can only be given legally if the therapeutic plan for their use is previously approved by the Ethics Committee and after informed consent from the patient/parents. Promising results have been obtained, particularly for sumatriptan in nasal spray formulation as well as for zolmitriptan and rizatriptan, showing a high tolerability and safety profile.
PMCID: PMC3451584
Migraine; Analgesics; Triptans
22.  Sumatriptan transdermal iontophoretic patch (NP101-Zelrix™): review of pharmacology, clinical efficacy, and safety in the acute treatment of migraine 
Migraine is a chronic, painful, and often disabling primary headache disorder, typically presenting with recurrent attacks that may be accompanied by a variety of neurological, gastrointestinal, and autonomic symptoms. Gastrointestinal symptoms in association with migraine including, nausea, vomiting, and gastroparesis, affect a large proportion of migraine sufferers. These symptoms may result in delays or inconsistencies in the absorption of oral treatments. Hence, the necessity for an innovative, non-invasive, parenteral delivery formulation for quick and effective treatment of migraine attacks is evident. Iontophoresis utilizes minimal amounts of electrical potential to support the fast transfer of ionized medication transdermally and into the general circulation. Two pharmacokinetic clinical trials have shown that iontophoretic delivery of sumatriptan through the skin produces quick and reproducible therapeutic plasma concentrations. A randomized, double-blind, multicenter, phase III study demonstrated superior efficacy versus placebo and excellent tolerability, with no triptan-related adverse events. The proportion of patients that were pain-free at 2 h post-treatment was 18% for the sumatriptan patch vs 9% for placebo (P = 0.0092; number needed to treat = 11.1). Upon approval from the Food and Drug Administration and other regulatory authorities, the iontophoretic transdermal delivery of sumatriptan will be a good choice for patients experiencing poor absorption of oral medication often associated with migraine and/or for those with intolerable triptan-related adverse events.
PMCID: PMC3460671  PMID: 23055737
iontophoretic patch; migraine; migraine treatment; sumatriptan; transdermal patch
23.  Evidence-based guideline update: Pharmacologic treatment for episodic migraine prevention in adults 
Neurology  2012;78(17):1337-1345.
To provide updated evidence-based recommendations for the preventive treatment of migraine headache. The clinical question addressed was: What pharmacologic therapies are proven effective for migraine prevention?
The authors analyzed published studies from June 1999 to May 2009 using a structured review process to classify the evidence relative to the efficacy of various medications available in the United States for migraine prevention.
Results and Recommendations:
The author panel reviewed 284 abstracts, which ultimately yielded 29 Class I or Class II articles that are reviewed herein. Divalproex sodium, sodium valproate, topiramate, metoprolol, propranolol, and timolol are effective for migraine prevention and should be offered to patients with migraine to reduce migraine attack frequency and severity (Level A). Frovatriptan is effective for prevention of menstrual migraine (Level A). Lamotrigine is ineffective for migraine prevention (Level A).
PMCID: PMC3335452  PMID: 22529202
24.  Cephalalgiaphobia: a possible specific phobia of illness 
Psychiatric comorbidity, mainly anxiety and depression, are common in chronic migraine (CM). Phobias are reported by half of CM patients. Phobic avoidance associated with fear of headache or migraine attack has never been adequately described. We describe 12 migraine patients with particular phobic-avoidant behaviours related to their headache attacks, which we classified as a specific illness phobia, coined as cephalalgiaphobia. All patients were women, mean age 42, and all had a migraine diagnosis (11 CM, all overused acute medications). Patients had either a phobia of a headache attack during a pain-free state or a phobia of pain worsening during mild headache episodes. Patients overused acute medication as phobic avoidance. It is a significant problem, associated with distress and impairment, interfering with medical care. Cephalalgiaphobia is a possible specific phobia of illness, possibly linked to progression of migraine to CM and to acute medication overuse headache.
PMCID: PMC3476114  PMID: 17361383
Phobia; Migraine; Anxiety disorders; Illness phobia; Comorbidity
25.  Patient outcome in migraine prophylaxis: the role of psychopharmacological agents 
Migraine is a serious illness that needs correct treatment for acute attacks and, in addition, a treatment prophylaxis, since patients with migraine suffer during acute attacks and also between attacks.
A systematic review of the most relevant clinical trials of migraine headache and its epidemiology, pathophysiology, comorbidity, and prophylactic treatment (medical and nonmedical) was carried out using “Medline” and “PsychINFO” from 1973 to 2009. Approximately 110 trials met our inclusion criteria and were included in the current review.
The most effective pharmacological treatment for migraine prophylaxis is propranolol and anticonvulsants such as topiramate, valproic acid, and amitriptyline. Nonmedical treatments such as acupuncture, biofeedback, and melatonin have also been proposed. Peripheral neurostimulation has been suggested for the treatment of chronic daily headache that does not respond to prophylaxis and for the treatment of drug-resistant primary headache. The majority of the pharmacological agents available today have limited efficacy and may cause adverse effects incompatible with long-term use.
The review was limited by the highly variable and often insufficient reporting of the complex outcome data and by the fact that migraine prophylaxis trials typically use headache diaries to monitor the course of the disease. The results of the different studies were also presented in different ways, making comparison of the results difficult.
An adequate prophylaxis is crucial in reducing disability and preventing the evolution of the problem into a chronic progressive illness. The implications of the present findings were discussed.
PMCID: PMC3417910  PMID: 22915957
migraine; prophylaxis; pharmacological agents; nonmedical treatments; outcome

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