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.     

Medical therapy for menstrual migraine

A menstrual migraine occurs in approximately 7-10 % of women suffering from migraine. The migraine occurs from 2 days before until 3 days after the end of the menstrual period. The choice of treatment depends on the duration of the attack, which ranges from 3 to 7 days. An attack of up to 3 days duration should be treated with acetylsalicylic acid, ergotamine tartrate or naproxen, each in combination with an antiemetic (domperidone, metoclopramide). If there is no response, sumatriptan can be administered orally (25-100 mg) or subcutaneously (6 mg). In the attacks continue for more than 3 days, short-term prophylaxis with naproxen or the application of an estrogen-containing patch is indicated. Neither ovulation inhibitors nor traditional migraine prophylaxis has an influence on menstrual migraine. Patients should keep a headache diary. Short-term prophylaxis with ergotamine tartrate or tamoxifen is obsolete.     

Ergotamine vs. metoclopramide vs. their combination in acute migraine attacks

The effect of ergotamine tartrate was compared with that of the antiemetic agent metoclopramide and with those of two combinations in a double-blind trial of 24 adult female patients with migraine. The following combinations of the drugs were used in oral administration in a total of 176 acute migraine attacks: (a) Ergotamine 1 mg, (b) Metoclopramide 20 mg, (c) Ergotamine 1 mg + metoclopramide 20 mg, (d) Ergotamine 2 mg + metoclopramide 20 mg. The duration of attacks was significantly shorter on both of the combinations compared with the single drugs. The intensity of the pain was somewhat weaker and the appearance of nausea and vomiting somewhat but not significantly less during the combination treatments. In their overall opinion the patients favored the 2 mg + 20 mg combination significantly more than the others. Both ergotamine and metoclopramide are efficient in acute migraine attacks. Their combination seems to enhance the therapeutic response in some respects.     

An instrument to assess patient perceptions of satisfaction with acute migraine treatment (EXPERT Study)

(Headache 2011;51:590‐601) Objective.— The objective of the nationwide EXPERT survey carried out in France in 2005 was to compare satisfaction with treatment with treatment effectiveness in migraine patients consulting general practitioners (GPs) for migraine, and to establish an instrument to easily evaluate the adequacy of acute treatment of migraine. Background.— Many migraine patients feel satisfied with their current acute treatment of migraine whereas objective evaluation reveals poor treatment effectiveness. Methods.— A total of 2108 GPs included 11,274 migraine patients. Satisfaction with treatment was evaluated using a 4‐point verbal scale and a 10‐cm visual analog scale (VAS). Treatment effectiveness was assessed by the 4‐item questionnaire designed by the French Medico‐Economic Evaluation Service (ANAES) and the French Society for the Study of Migraine Headache (SFEMC). Results.— In total, 5224 patients (49.8%) stated that they were satisfied with their treatment. Mean VAS score was 5.1. Only 17% of patients (1789/10,539) gave positive responses at the 4 questions of the ANAES/SFEMC questionnaire. VAS score was high for patients satisfied with their treatment and with good treatment effectiveness. Two VAS thresholds were determined using receiver operating characteristic curves that allowed easy identification, with high sensitivity and specificity, of patients satisfied/dissatisfied with their current treatment and with good/poor treatment effectiveness. Based on EXPERT data, this instrument showed that only 16% of patients using triptans (597/3719) were dissatisfied and reported poor treatment effectiveness, whereas treatment was inadequate for 63% of those using aspirin or nonsteroidal anti‐inflammatory drugs (1882/2992), 74% of those using paracetamol or other analgesics (2229/2998), and 53% of those using ergotamine (253/474). Conclusions.— The new instrument should allow easy identification in general practice of the patients receiving an effective or ineffective acute treatment of migraine and thus facilitate the implementation of treatment guidelines for migraine.     

Abortive Migraine Therapy With Oral Naproxen Sodium Plus Metoclopramide Plus Ergotamine Tartrate With Caffeine

The oral tablet combination, (550 mgs. of naproxen sodium plus 10 mgs. of metoclopramide plus 1 mg. of ergotamine tartrate plus 100 mgs. of caffeine), was retrospectively studied in 63 patients who used it to abort migraine headaches. On the average, 84% of the headaches were totally aborted; minor side effects occurred in 40% of the patients, and 87% of the patients considered the combination superior to all prior treatments.     

Bioavailability and antimigraine efficacy of effervescent ergotamine

SYNOPSIS
In about 20% of migraine patients treatment with enterally administrated ergotamine tartrate proves unsuccessful. One of the causes for this might be a poor systemic availability of the drug from the ordinary solid tablets. The present study aimed to investigate the bioavailability and the therapeutic value of ergotamine tartrate in effervescent form.
In twenty volunteers the plasma ergotamine levels were measured by using a radioimmunoassay after oral administration of 2.0 mg ergotamine tartrate combined with 50.0 mg caffeine in effervescent form. Measurable plasma drug levels were found in 14 (70%) of the subjects and the mean maximum plasma ergotamine level of 0.45 ng/ml was achieved at 30 minutes.
In the clinical part of the study 25 migraine patients treated their migraine attacks with effervescent ergotamine. The therapeutic value of it was considered as good by 9, moderate by 11 and poor by 5 of the patients. Among 18 of them the therapeutic effect seemed to be equal to their earlier ergotamine medications. The results indicate that the plasma pharmacokinetics of ergotamine tartrate in effervescent form is similar to and possibly faster on the absorptive phase than that reported earlier after enteral administration. In patients who do not gain benefit from the usual ergotamine tablets or suppositories, effervescent ergotamine would appear to be an alternative worth consideration.     

Recognition and therapeutic management of migraine in 2004, in France: results of FRAMIG 3, a French nationwide population-based survey

OBJECTIVE: To evaluate the proportion of migraineurs who are self-aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self-awareness of migraine, and to assess the influence of these factors on migraine attacks. BACKGROUND: New recommendations for migraine diagnosis and medical management were released in 2003 by the French medicoeconomic evaluation service (ANAES). In addition, the revised classification of headache disorders recently issued by the International Headache Society includes probable migraine as a form of migraine. However, strict and probable migraine now appear to be part of the same spectrum of disease. METHODS: Subjects with migraine (strict or probable) according to the revised classification were identified by a postal questionnaire from a large representative sample of the French adult population. Migraine-related disability was assessed using the MIDAS questionnaire, anxiety and depression by the Hospital Anxiety and Depression scale (HADS), and health-related quality of life (HRQoL) by the 8 concepts of the Short-Form 12 (SF-12) questionnaire. Migraine management was assessed according to the use of recommended or nonrecommended treatments, and treatment efficacy according to the set of 4 questions designed by the ANAES. RESULTS: Of the 10,532 subjects interviewed, 1,179 subjects (21.3%) were identified as migraineurs. Sixty percent of all migraine subjects were not self-aware that they had migraine. Medical consultation, duration of migraine history, severe intensity of attacks, impact on daily living, and female gender promoted self-awareness of migraine. On the other hand, HRQoL and anxiety and depression scores were not different between subjects self-aware or not self-aware of migraine. Only 20% of all migraine subjects were medically followed-up. Quality of the first medical consultation appears determinant for continued consulting. Subjects self-aware of migraine more frequently used recommended acute treatments of migraine, which proved more effective than nonrecommended treatments as assessed according to the ANAES set of questions. CONCLUSIONS: Migraine medical diagnosis and follow-up remain low in France. Careful medical consultation is a prime factor for migraine subject self-awareness of migraine, continued consultation, and use of recommended medications for the treatment of migraine attacks.     

Acute migraine attack therapy: comparison of naproxen sodium and an ergotamine tartrate compound

The efficacy of safety of naproxen sodium and ergotamine tartrate were compared for the treatment of acute migraine attack in a randomized, parallel trial with 114 participating patients. At the start of symptoms, patients took either three tablets of naproxen sodium (275 mg each) or one of an ergotamine combination (containing 2 mg ergotamine tartrate, 91.5 mg caffeine, and 50 mg cyclizine chlorhydrate). Patients were followed for three months or until six attacks were monitored, whichever came first. Both medications substantially shortened the duration of migraine attacks and reduced the severity of symptoms. When the test medications were taken within 2 h of onset of attack, naproxen sodium was statistically significantly more effective than the ergotamine combination in reducing the severity of headache pain, nausea, and lightheadedness. The ergotamine combination was associated with significantly more vomiting, need for rescue medication, and side effects than was naproxen sodium. Four patients required discontinuation of the ergotamine combination and one of naproxen sodium. Both patients and investigators rated tolerance for naproxen sodium as superior to tolerance for the ergotamine combination. Naproxen sodium seems to be an effective and safe treatment for migraine attacks.     

The influence of ergotamine abuse on psychological and cognitive functioning

Migraine patients abusing ergotamine often have chronic daily headaches associated with tiredness, sleep and memory disturbances, and reduced general well-being. We quantified psychological and cognitive functioning in 12 migraine patients with and 12 without ergotamine abuse (> or = 5 days/week for > or = 6 months) and 12 healthy controls. Psychological functioning assessed by Symptom Checklist-90 (SCL-90) and Profile Of Mood State (POMS), was impaired in ergotamine abusers compared to healthy controls. Cognitive functioning divided into four domains: attention (critical flicker frequency analysis and mental control subscale of the Wechsler Memory Scale (WMS), speed of information processing (reaction time tasks and lexical decision tasks), memory (four subscales of the WMS) and cognitive flexibility (trailmaking test and WMS digits backwards), was impaired in ergotamine abusers in speed of information processing and cognitive flexibility. These differences disappeared after correction for total SCL-90 scores. In conclusion, ergotamine abuse is associated with high psychological distress but not with structural impaired cognitive functioning.     

Ergotamine Dependency- a Review

SYNOPSIS
Ergotamine tartrate has been recognized as the drug of first choice for the treatment of acute attacks of migraine. This paper draws attention to a common but poorly delineated state of addiction that can develop when ergotamine tartrate usage exceeds two or three days per week. This syndrome is characterized by a self-sustaining, rhythmic headache/medication cycle, with daily or almost daily migraine headaches and the irresistible and predictable use of ergotamine tartrate as the only means of alleviating the headache attacks. This report further delineates the clinical features, criteria for recognition, and treatment alternatives for this syndrome. In order to avoid this condition, usage should be restricted to 2 days per week.     

Favorable outcome of early treatment of new onset child and adolescent migraine-implications for disease modification

There is evidence that the prevalence of migraine in children and adolescents may be increasing. Current theories of migraine pathophysiology in adults suggest activation of central cortical and brainstem pathways in conjunction with the peripheral trigeminovascular system, which ultimately results in release of neuropeptides, facilitation of central pain pathways, neurogenic inflammation surrounding peripheral vessels, and vasodilatation. Although several risk factors for frequent episodic, chronic, and refractory migraine have been identified, the causes of migraine progression are not known. Migraine pathophysiology has not been fully evaluated in children. In this review, we will first discuss the evidence that early therapeutic interventions in the child or adolescent new onset migraineur, may halt or limit progression and disability. We will then review the evidence suggesting that many adults with chronic or refractory migraine developed their migraine as children or adolescents and may not have been treated adequately with migraine-specific therapy. Finally, we will show that early, appropriate and optimal treatment of migraine during childhood and adolescence may result in disease modification and prevent progression of this disease.     

Transformed migraine and medication overuse in a tertiary headache centre--clinical characteristics and treatment outcomes

Studies suggest that a substantial proportion of headache sufferers presenting to headache clinics may overuse acute medications. In some cases, overuse may be responsible for the development or maintenance of a chronic daily headache (CDH) syndrome. The objectives of this study are to evaluate patterns of analgesic overuse in patients consulting a headache centre and to compare the outcomes in a group of patients who discontinued medication overuse to those of a group who continued the overuse, in patients with similar age, sex and psychological profile. We reviewed charts of 456 patients with transformed migraine (TM) and acute medication overuse defined by one of the following criteria: 1. Simple analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically considered overuse > 1 tablet per day for > 5 days per week. Patients who were able to undergo detoxification and did not overuse medication (based on the above definition) after one year of follow-up were considered to have successful detoxification (Group 1). Patients who were not able to discontinue offending agents, or returned to a pattern of medication overuse within one year were considered to have unsuccessful detoxification (Group 2). We compared the following outcomes after one year of follow-up: Number of days with headache per month; Intensity of headache; Duration of headache; Headache score (frequency x intensity). The majority of patients overused more than one type of medication. Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight (10.5%) subjects took >10 tablets per day. Considering patients seen in the last 5 years, we found the following overused substances: Butalbital containing combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%; Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%; Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%) were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The comparison between groups 1 and 2 after one year of follow-up showed a decrease in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P < 0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and 14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully detoxified subjects in Group 1 returned to an episodic pattern of migraine, compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing guidelines for patients with frequent headaches are urgently needed. Successful detoxification is necessary to ensure improvement in the headache status when treating patients who overuse acute medications.     

Sublingual Flunarizine: a New Effective Management of the Migraine Attack. A Comparison versus Ergotamine

SYNOPSIS
Flunarizine was found to be effective in the acute treatment of isosorbide dinitrate induced migraine attacks, when given in a dosage of 10 mg sublingually.
The present study consists of two parts: in the first preliminary investigation, 7 out of 8 migraine patients who developed a typical migraine attack after isosorbide dinitrate were relieved of pain within about 10 minutes. On the basis of this result a second, randomized controlled open trial was performed, in which the acute efficacy of flunarizine was compared with ergotamine tartrate, 0.25 mg i.m., on 40 migraine patients. Flunarizine was found as effective as ergotamine (75% positive responses in the flunarizine group, 70% in the ergotamine group). The mean latency of the flunarizine effect was significantly lower than that of the ergotamine ( r < 0.001, Student's t test). Moreover sublingual flunarizine was found to be virtually devoid of side effects.     

Placebo-controlled double-blind trial of pirprofen and an ergotamine tartrate compound in migraine attacks

Sixty-one patients, 16 with classic and 45 with common migraine, were treated during three subsequent attacks with pirprofen, a new inhibitor of prostaglandin synthesis; an ergotamine tartrate compound; or placebo, in a randomized, double-blind multicentre study. Pain relief after a single dose and reduction of the attack intensity occurred most often with pirprofen in patients who needed more than one dose. Among them, however, the duration of attack was shortest with ergotamine. Working ability was well preserved with pirprofen, especially among patients with common migraine, and this treatment was ranked highest by the patients. However, no statistically significant differences were found between pirprofen and ergotamine. No serious side effects were observed with pirprofen. This study establishes the usefulness of pirprofen in the treatment of acute migraine.     

Tolfenamic Acid and Ergotamine Abuse

SYNOPSIS
Thirteen migraine patients using ergotamine tartrate on a daily basis for their headaches were found to have developed the so called "ergotamine headache," a dull constant headache always reappearing if the patient did not take their daily doses. They were treated with tolfenamic acid, an inhibitor of prostaglandin synthesis and action, combined with chlordiazepoxide during the acute withdrawal phase after discontinuing their daily habit of taking ergotamine. As a whole, the results of the discontinuation of the use of ergotamine were encouraging in the group of these patients showing a serious medical problem. None of the patients relapsed into ergotamine abuse, and during the subsequent 3–6 months nine of the patients also treated their migraine attacks solely with tolfenamic acid.     

Comparison of pharmacodynamic effects and plasma levels of oral and rectal ergotamine

Plasma levels and the vasoconstrictive effect of 1 mg ergotamine tartrate given as tablets or suppositories were compared. In a crossover study, eight male volunteers received tablets or suppositories containing ergotamine in a drug combination (Anervan) and, as a control, suppositories without ergotamine. Blood sampling and measurement of toe-arm systolic gradients with a strain-gauge technique were done for up to 6 h and again after 24 h and 48 h. Only 29 of 160 blood samples contained detectable (greater than 0.1 ng/ml) amounts of ergotamine, and kinetic comparison could not be performed. Only ergotamine-containing suppositories caused a significant (p less than 0.008) decrease in toe-arm systolic gradient which was significantly different (p less than 0.003) from the effects of ergotamine tablets and control suppositories. Rectal ergotamine is thus more biologically active, for the factor used, than oral ergotamine. We suggest that a rectal dose of 1 mg ergotamine tartrate should be tried as the initial dose in the treatment of migraine attacks.     

The GRIM2005 study of migraine consultation in France II. Psychological factors associated with treatment response to acute headache therapy and satisfaction in migraine

The objective of this analysis was to identify variables associated with treatment response in subjects with migraine. Data were collected from a sample of 10 000 subjects. A battery of questionnaires assessing clinical and psychological variables was completed. Migraine diagnosis was attributed using an algorithm based on the IHS criteria and treatment response using the ANAES criteria. We identified 1534 subjects, of whom 1443 were treated. For 54.2%, at least one ANAES criterion for treatment response was unfulfilled. Non-response was associated with female gender, high HIT-6 impact scores and high HAD psychological distress scores. The strongest associations with non-response were identified for four psychological variables: elevated scores on the CSQ catastrophization subscale and the 'Consequences' and 'Acceptance' dimensions of the Brief COPE, and low scores on the 'Positive Reinterpretation' Brief COPE dimension. In conclusion, many individuals with migraine respond inadequately to treatment. Behavioural interventions aimed at modifying coping strategies may improve outcome.     

Headache currents commentary

What Happens to the Old Headache Medicines? Rapoport AM, MD Old headache medicines never die; they either fade away or come back in disguise. The disguise is often a new route of administration, which may work better, faster, more completely, with fewer adverse events, and/or have certain other advantages. The clinical aspects of 3 of the oldest headache medicines (ergotamine tartrate, dihydroergotamine, and methysergide) will be discussed here. Sumatriptan will then be discussed as the prototype of the newest category of acute care therapy (triptans) for migraine. It will be compared with the older medications, and the new forms being developed will be briefly discussed. Diclofenac potassium for oral solution will be mentioned as the newest drug approved for migraine by the Food and Drug Administration and a possible alternative to triptans in patients with frequent headaches or those with contraindications to vasoconstrictors. Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan – Basic Science in Relation to Migraine Treatment Dahlöf C, Maassen Van Den Brink A. The 5‐hydroxytryptamine (5‐HT) receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5‐HT_1B, 5‐HT_1D, and 5‐HT_1F receptors. Ergotamine, dihydroergotamine and methysergide, as well as the “triptan” sumatriptan, are all agonists for these receptors. The receptor profile and degree of selectivity of these 4 drugs differ, which is reflected by their side effects that limit their use in the acute and prophylactic treatment of migraine. The acute antimigraine efficacy of these remedies is very much dependent on the formulation used where, in general, parenteral formulations are more effective in relieving the symptoms of a migraine attack.     

Characteristic and overlapping features of migraine and tension-type headache

OBJECTIVE: This epidemiological survey was conducted to investigate comprehensive characteristic and overlapping features of migraine and tension-type headache (TTH) disorders classified based on International Classification of Headache Disorders-II. METHODS: The stratified cohort of this study was composed of 2504 schoolchildren aged 10 to 17 years. A 38-item questionnaire inquiring all characteristic features of primary headache syndromes mandatory for classification was applied to selected 483 children with recurrent headache in the last 6 months. RESULTS: Migraine was diagnosed in 227 (47.0%) of 483 children and TTH in 154 (31.9%). Out of 125 children with definite migraine, 73 (58.4%) reported tension-type symptoms and 94 (68.1%) of 138 children with definite TTH reported migraine-type symptoms. Pressing pain (21%) and lack of aggravation of pain by physical activity (34%) were the major tension-type features in patients with migraine. Throbbing quality (43%) and aggravation by physical activity (30%) determined the main migraine-type features in patients with TTH. CONCLUSION: The frequent co-occurrence of migraine and TTH symptoms suggests the presence of a common pathogenesis.