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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.

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.

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.

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.

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.

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.

Background

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.

Discussion

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.

Conclusion

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.

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.

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.

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.

Methods

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.

Results

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.

Conclusions

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.

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.

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.

Introduction:

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.

Methods:

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.

Results:

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.

Limitations:

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.

Discussion:

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.

Chronic migraine management almost always requires daily oral preventative medication with potential adverse effects. Daily oral preventative therapy may also not be effective in terminating chronic migraine. Chronic central sensitisation caused by repetitive migraine attacks in a young person may lower the threshold for future migraine episodes leading to an intractable and debilitating disease course. The objective was to determine if short–term parenteral dihydroergotamine, dexamethasone and hydroxyzine can terminate chronic migraine and be followed by a continuous respite or conversion to a more benign episodic form without the need for daily oral preventative medication (“carry–over effect”). We treated ten patients, seven adolescents and three adults, with parenteral dihydroergotamine, dexamethasone and hydroxyzine given once a week for a maximum of three weeks. No oral preventative daily medication was administered. The setting was a private practice. Chronic migraine was terminated in all 7 adolescents. Their post–treatment course was converted to a more benign episodic migraine course and no adolescent required daily oral migraine preventative therapy for significantly long carry–over post–treatment observational periods. None of the three adult chronic migraine cases could be terminated satisfactorily as they all required daily oral preventative therapy. In the adolescent group only, this strategy terminated chronic migraine and resulted in a significant carry–over effect that appeared to favourably modify the long–term course without the need for daily pharmacological, potentially toxic, preventive therapy. Although this is a very small study, which requires confirmation by a larger controlled study, our data suggest a significant carryover effect in the young migraineur by administering short–term parenteral dihydroergotamine, dexamethasone and hydroxyzine.

The objective of this study is to analyse our experience in the treatment of refractory chronic migraine (CM) with onabotulinumtoxinA (BTA) and specifically in its effects over disabling attacks. Patients with CM and inadequate response or intolerance to oral preventatives were treated with pericranial injections of 100 U of TBA every 3 months. The dose was increased up to 200 U in case of no response. The patients kept a headache diary. In addition, we specifically asked on the effect of BTA on the frequency of disabling attacks, consumption of triptans and visits to Emergency for the treatment of severe attacks. This series comprises a total of 35 patients (3 males), aged 24–68 years. All except three met IHS criteria for analgesic overuse. The number of sessions with BTA ranged from 2 to 15 (median 4) and nine (26%) responded (reduction of >50% in headache days). However, the frequency of severe attacks was reduced to an average of 46%. Oral triptan consumption (29 patients) was reduced by 50% (from an average of 22 to 11 tablets/month). Those six patients who used subcutaneous sumatriptan reduced its consumption to a mean of 69% (from 4.5 to 1.5 injections per month). Emergency visits went from an average of 3 to 0.4 per trimester (−83%). Six patients complained of mild adverse events, transient local cervical pain being the most common. Although our data must be taken with caution as this is an open trial, in clinical practice treatment of refractory CM with BTA reduces the frequency of disabling attacks, the consumption of triptans and the need of visits to Emergency, which makes this treatment a profitable option both clinically and pharmacoeconomically.

The objective of this study is to analyse our experience in the treatment of refractory chronic migraine (CM) with onabotulinumtoxinA (BTA) and specifically in its effects over disabling attacks. Patients with CM and inadequate response or intolerance to oral preventatives were treated with pericranial injections of 100 U of TBA every 3 months. The dose was increased up to 200 U in case of no response. The patients kept a headache diary. In addition, we specifically asked on the effect of BTA on the frequency of disabling attacks, consumption of triptans and visits to Emergency for the treatment of severe attacks. This series comprises a total of 35 patients (3 males), aged 24–68 years. All except three met IHS criteria for analgesic overuse. The number of sessions with BTA ranged from 2 to 15 (median 4) and nine (26%) responded (reduction of >50% in headache days). However, the frequency of severe attacks was reduced to an average of 46%. Oral triptan consumption (29 patients) was reduced by 50% (from an average of 22 to 11 tablets/month). Those six patients who used subcutaneous sumatriptan reduced its consumption to a mean of 69% (from 4.5 to 1.5 injections per month). Emergency visits went from an average of 3 to 0.4 per trimester (−83%). Six patients complained of mild adverse events, transient local cervical pain being the most common. Although our data must be taken with caution as this is an open trial, in clinical practice treatment of refractory CM with BTA reduces the frequency of disabling attacks, the consumption of triptans and the need of visits to Emergency, which makes this treatment a profitable option both clinically and pharmacoeconomically.

Background:

In the clinical trial setting, oral rizatriptan 10 mg has greater efficacy than other oral triptans in freedom from migraine headache pain 2 h after dosing.

Objective:

The study objective is to compare the effectiveness of rizatriptan 10 mg and other oral triptans for acute migraine attack in a naturalistic setting.

Methods:

A total of 673 patients took rizatriptan 10 mg or their usual-care oral triptans for two migraine attacks in a sequential, cross-over manner and recorded outcomes using a diary and a stopwatch. Mean and median times to pain relief (PR) and pain freedom (PF) for rizatriptan and other oral triptans were compared. The effect of rizatriptan on times to PR and PF, adjusting for potential confounding factors (treatment sequence, treatment order and use of rescue medication), was computed via a Cox proportional hazard model.

Results:

Significantly, more patients taking rizatriptan achieved both PR and PF within 2 h after dosing than other oral triptans. Times to PR and PF were shorter with rizatriptan than with other oral triptans (median time to PR: 45 vs. 52 min, p < 0.0001; median time to PF: 100 vs. 124 min, p < 0.0001). The adjusted proportional hazard ratios (rizatriptan vs. other oral triptans) for times to PR and PF were 1.32 (95% CI: 1.22–1.44) and 1.27 (95% CI: 1.16–1.39) respectively.

Conclusion:

The times to PR and PF in a ‘naturalistic’ setting were significantly shorter for patients treating a migraine attack with rizatriptan 10 mg than with other oral triptans.

Migraine is a common primary headache disorder often associated with significant disability. While many individuals are able to limit therapy to acute treatment of attacks, others need medication to reduce the attack frequency and/or severity. Evidence-based guidelines exist regarding indications and goals for migraine preventive treatment. The specific prophylactic approach needs to be individualized taking into account multiple variables. Medications used in this task vary widely in proven efficacy and presumed mechanisms of action. This review’s goal is to discuss the issues that guide the decision-making process in migraine preventive treatment.

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.

Background

Migraine affects approximately 20% of the population. Conventional care for migraine is suboptimal; overuse of medications for the treatment of episodic migraines is a risk factor for developing chronic daily headache. The study of non-pharmaceutical approaches for prevention of migraine headaches is therefore warranted. Craniosacral therapy (CST) is a popular non-pharmacological approach to the treatment or prevention of migraine headaches for which there is limited evidence of safety and efficacy. In this paper, we describe an ongoing feasibility study to assess the safety and efficacy of CST in the treatment of migraine, using a rigorous and innovative randomized controlled study design involving low-strength static magnets (LSSM) as an attention control intervention.

Methods

The trial is designed to test the hypothesis that, compared to those receiving usual care plus a treatment with low-strength static magnets (attention-control complementary therapy), subjects receiving usual medical care plus CST will demonstrate significant improvement in: quality-of-life as measured by the Headache Impact Test (HIT-6); reduced frequency of migraine; and a perception of clinical benefit. Criteria for inclusion are either gender, age > 11, English or Spanish speaking, meeting the International Classification of Headache Disorders (ICHD) criteria for migraine with or without aura, a headache frequency of 5 to 15 per month over at least two years. After an 8 week baseline phase, eligible subjects are randomized to either CST or an attention control intervention, low strength static magnets (LSSM). To evaluate possible therapist bias, videotaped encounters are analyzed to assess for any systematic group differences in interactions with subjects.

Results

169 individuals have been screened for eligibility, of which 109 were eligible for the study. Five did not qualify during the baseline phase because of inadequate headache frequency. Nineteen have withdrawn from the study after giving consent.

Conclusion

This report endorses the feasibility of undertaking a rigorous randomized clinical trial of CST for migraine using a standardized CST protocol and an innovative control protocol developed for the study. Subjects are able and willing to complete detailed headache diaries during an 8-week baseline period, with few dropouts during the study period, indicating the acceptability of both interventions.

Trial Registration

ClinicalTrials.gov NCT00665236

Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers.

Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers.

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.

PROBLEM ADDRESSED: Headache is a common clinical disorder. Nearly 50% of patients with headaches use prescription medications, and 90% regularly use nonprescription drugs. Medication-induced headaches (MIH) are chronic daily headaches caused by overuse of medicine. OBJECTIVES: To summarize the diagnostic criteria for MIH, to determine the investigations necessary to confirm the diagnosis and exclude other possible diagnoses, and to establish recommendations for managing MIH. MAIN FINDINGS: Diagnosis of MIH is based on patient's history and the clinical characteristics of the headache. Treatment includes patient education and support, withdrawal of offending medications, relief of withdrawal symptoms, and specific treatment of residual headache. When migraine and other causes of headache are adequately addressed, patients will not seek additional pain relief. CONCLUSION: Medication-induced headache is preventable. The key to prevention is appropriate drug therapy to relieve the primary headache. All patients with MIH can be treated and most cured.

Migraine is a common neurological disorder often treated with triptans. Triptan overuse can lead to increased frequency of headache in some patients, a phenomenon termed medication overuse headache. Previous preclinical studies have demonstrated that repeated or sustained triptan administration for several days can elicit persistent neural adaptations in trigeminal ganglion cells innervating the dura, prominently characterized by increased labelling of neuronal profiles for calcitonin gene related peptide. Additionally, triptan administration elicited a behavioural syndrome of enhanced sensitivity to surrogate triggers of migraine that was maintained for weeks following discontinuation of drug, a phenomenon termed ‘triptan-induced latent sensitization’. Here, we demonstrate that triptan administration elicits a long-lasting increase in identified rat trigeminal dural afferents labelled for neuronal nitric oxide synthase in the trigeminal ganglion. Cutaneous allodynia observed during the period of triptan administration was reversed by NXN-323, a selective inhibitor of neuronal nitric oxide synthase. Additionally, neuronal nitric oxide synthase inhibition prevented environmental stress-induced hypersensitivity in the post-triptan administration period. Co-administration of NXN-323 with sumatriptan over several days prevented the expression of allodynia and enhanced sensitivity to stress observed following latent sensitization, but not the triptan-induced increased labelling of neuronal nitric oxide synthase in dural afferents. Triptan administration thus promotes increased expression of neuronal nitric oxide synthase in dural afferents, which is critical for enhanced sensitivity to environmental stress. These data provide a biological basis for increased frequency of headache following triptans and highlight the potential clinical utility of neuronal nitric oxide synthase inhibition in preventing or treating medication overuse headache.