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.     

Naproxen Sodium Versus Ergotamine Tartrate in the Treatment of Acute Migraine Attacks

A double-blind parallel study compared the efficacy and safety of naproxen sodium (NPX) and ergotamine tartrate (ERG) as abortive therapy for acute headache in 79 patients with classical or common migraine. The design study was of the double-blind design. Forty-two patients completed the study. Discontinuation of treatment was generally due to lack of efficacy or adverse reactions. NPX was significantly better than ERG in the overall efficacy of treatment rated by the patients (p less than 004). NPX was comparable to ERG in reducing the severity and duration of the headache and its associated symptoms. In classical migraine, NPX was better than ERG in alleviating the severity of headache. Patients in the NPX group tended to use less rescue medication. There was no significant difference in the frequency of side-effects reported by the patients under NPX or ERG. This study demonstrates that NPX is as safe as ERG, and somewhat more effective in acute migraine attacks (although the difference is not statistically significant) and that migrainous patients tend to prefer NPX to ERG in treating their acute migraine headaches.     

How to Apply the AHS Evidence Assessment of the Acute Treatment of Migraine in Adults to your Patient with Migraine

The “Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies” provides levels of evidence for medication efficacy for acute treatment of migraine. The goal of this companion paper is to provide guidance on how to choose between evidence‐based treatment options, and, based on the clinical characteristics of the patient and their migraine attacks, to provide guidance on designing an individualized strategy for managing migraine attacks. The acute pharmacological treatments described in the American Headache Society evidence assessment can be divided into those initially taken by the patient during the headache phase of the migraine attack, those taken by the patient later in the attack when initial treatments fail, and those administered intravenously or intramuscularly in urgent care settings. Medications taken initially by patients in the headache phase include nonspecific analgesics such as acetaminophen and nonsteroidal anti‐inflammatory drugs (NSAIDs), triptans, and dihydroergotamine (DHE). A stratified approach to treatment is advised, with the choice of medication based on the patient's treatment needs, taking into consideration the attack severity, presence of associated symptoms such as nausea and vomiting, and the degree of migraine‐related disability. Individuals with migraine may find reassurance in having a “back‐up plan” in the event of an initial acute treatment failure. For those individuals who had a partial response to the initial acute treatment, a second dose might be indicated. When the initial treatment does not provide meaningful and sustained benefits, a treatment from a different medication class is typically chosen. Depending upon the initial treatment used, this might include NSAIDs, triptans, or DHE. Opioids or acetaminophen in combination with codeine or tramadol can be considered as part of the “back‐up plan,” provided they are used infrequently. When all patient administered treatments have failed and moderate to severe migraine symptoms remain, some individuals seek treatment in urgent care settings. The intravenous administration of antiemetics with or without an intravenous or intramuscular NSAID or DHE, or an intramuscular opioid can be considered. Patients with migraine should be encouraged to treat migraine pain early, and avoid overuse of medications.     

Oral Rizatriptan Versus Oral Sumatriptan: A Direct Comparative Study in the Acute Treatment of Migraine

Rizatriptan is a potent, oral, 5-HT_1B/1D agonist with more rapid absorption and higher bioavailability than oral sumatriptan. It was postulated that this would result in more rapid onset of effect. This randomized, double-blind, triple-dummy, parallel-groups study compared rizatriptan 5 mg, rizatriptan 10 mg, sumatriptan 100 mg, and placebo in 1268 outpatients treating a single migraine attack. Headache relief rates after rizatriptan 10 mg were consistently higher than sumatriptan at all time points up to 2 hours, with significance at 1 hour (37% versus 28%, P =0.010). All active agents were significantly superior to placebo with regard to headache relief and pain freedom at 2 hours ( P ≤0.001). The primary efficacy endpoint of time to pain relief through 2 hours demonstrated that, after adjustment for age imbalance, rizatriptan 10 mg had earlier onset than sumatriptan 100 mg ( P =0.032; hazard ratio 1.21). Rizatriptan 10 mg was also superior to sumatriptan on pain-free response ( P =0.032), reduction in functional disability ( P =0.015), and relief of nausea at 2 hours ( P =0.010). Significantly fewer drug-related clinical adverse events were reported after rizatriptan 10 mg (33%, P =0.014) compared with sumatriptan 100 mg (41%). We conclude that rizatriptan 10 mg has a rapid onset of action and relieves headache and associated symptoms more effectively than sumatriptan 100 mg.     

Remote Electrical Neuromodulation (REN) for the Acute Treatment of Migraine

There is a significant unmet need for novel, effective, and well-tolerated acute migraine treatments. Remote electrical neuromodulation (REN) is a non-pharmacological, non-invasive, acute migraine treatment that stimulates upper arm peripheral nerves to induce conditioned pain modulation – an endogenous analgesic mechanism in which a conditioning stimulation inhibits pain in remote body regions. This review presents the method of action and the clinical data of REN and discusses its potential patient benefits. The clinically meaningful efficacy, together with a very favorable safety profile, suggests that REN may offer a promising alternative for the acute treatment of migraine and could be considered first-line treatment in some patients.     

Dose Range-Finding Studies With Frovatriptan in the Acute Treatment of Migraine

Objective.—To determine the optimum dose of frovatriptan for the acute treatment of migraine.
Background.—Frovatriptan is a new triptan developed for the acute treatment of migraine. The dose-response characteristics and safety of frovatriptan have been investigated across a broad range of doses from 0.5 to 40 mg.
Design.—Two randomized, placebo-controlled, double-blind, parallel-group trials, with a total of 1453 patients, were performed to determine the optimal dose of the 5-HT_1B/1D agonist, frovatriptan, for the acute treatment of migraine. The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg in the low-dose study.
Results.—At 2 hours postdosing for initial moderate or severe headache (International Headache Society grades 2 or 3), there was an approximate two-fold difference in the proportion of patients taking frovatriptan doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours postdose, and 2.5 mg was identified as the lowest effective dose for the relief of migraine and accompanying symptoms. Above 2.5 mg, no dose-response relationship was observed for any efficacy parameters. There was an increase in the incidence of adverse events from 10 mg and above, but the vast majority were rated as mild in severity and did not impact upon tolerability in a significant manner.
Conclusions.—Frovatriptan was well tolerated throughout the dose range of 0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and tolerability for the acute treatment of migraine.     

Efficacy and Safety of 400 and 800 mg Etodolac vs. 1,000 mg Paracetamol in Acute Treatment of Migraine: A Randomized,Double‐blind,Crossover, Multicenter,Phase III Clinical Trial

Aim: We aimed to determine the efficacy and safety of etodolac, in acute migraine attacks in comparison with paracetamol (acetaminophen). Methods: We designed a randomized, double‐blind, crossover phase III clinical trial for patients diagnosed with migraine for at least 1 year, according to ICHD‐II criteria. Two hundred and twenty‐nine adult patients having 2 to 8 attacks monthly from 17 centers were included. The patients were instructed to use 3 attack treatment packages consisting of 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac on 3 migraine attacks of moderate–severe intensity each in a 3‐month treatment period, interchangeably. Results: Any pain medication was used in 1,570 migraine attacks while study treatments were used in 1,047 attacks. The results for 1,000 mg paracetamol, 400 mg etodolac, and 800 mg etodolac were as follows: response of headache at 2 hours 44.9%, 48.3% and 46.1%; pain‐free at 2 hours 19.2%, 19.3% and 24.1%; sustained pain‐free from 2 to 24 hours 34.3%, 38.3% and 41.1%; relapse rates in 2 to 24 hours 7.3%, 14.3% and 9.7%. There were no statistically significant differences between the groups regarding the headache response, pain‐free, sustained pain‐free, and relapse rates. Nausea, vomiting, phonophobia, or photophobia decreased similarly in all groups within 24 hours of treatment administration. Drug‐related adverse events were noted in 8 patients with 1,000 mg paracetamol, in 9 patients with 400 mg etodolac and in 9 patients for 800 mg etodolac during the study. Comment: Our study showed that etodolac is a safe and effective alternative in acute migraine treatment and showed comparable efficacy to paracetamol 1,000 mg. Etodolac may be considered as an alternative option for acute treatment of migraine.     

Comparison of Dihydroergotamine With Metoclopramide Versus Meperidine With Promethazine in the Treatment of Acute Migraine

Migraineurs often seek office-based treatment for acute headache. To compare the efficacy and side effect profile, we entered 27 migraineurs into a prospective, randomized, double-blind study where each patient received either 75 mg meperidine with 25 mg promethazine IM or .5 mg dihydroergotamine with 10 mg metoclopramide IV. After I hour, pain relief was similar in the two groups, but side effects were significantly greater in the meperidine with promethazine regimen group. The dihydroergotamine with metoclopramide regimen is effective, and has minimal side effects, making it an attractive method for office-based treatment of acute migraine.     

Acute Treatment of Basilar‐Type Migraine With Greater Occipital Nerve Blockade

(Headache 2010;50:1057‐1069) Basilar‐type migraine (BTM) precludes use of migraine‐specific medications such as triptans and ergots based on concerns originating from the vascular theory of migraine, although data supporting this contraindication are lacking. Availability of effective treatments for acute BTM is limited. We report a case of BTM aborted with greater occipital nerve (GON) blockade given in the setting of prominent suboccipital tenderness. GON blockade may provide an additional option in acute management of BTM. It may be particularly useful when associated with prominent ipsilateral suboccipital tenderness.     

Acute Confusional Migraine May Be a Presenting Feature of CADASIL

Objective.— Characterize the phenomenon of acute confusional migraine (ACM) among Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients and emphasize the possibility of CADASIL in adults with ACM.
Background.— ACM, well described in children, has rarely been reported in adults. Although 30-60% of CADASIL patients have migraine, acute confusional state during migraine has not been described. We describe 7 patients with ACM that complicated up to 50% of the migraine episodes.
Design/Methods.— Detailed neurologic evaluation was performed in 20 CADASIL patients; International Classification of Headache Disorders 2nd edition criteria were used to diagnose migraine.
Results.— The mean age was 51 years. Fourteen patients reported headache and 11 met the criteria for migraine (mean age of onset 25). Seven patients experienced concomitant confusion, within 3 years of migraine onset. Confusion occurred either abruptly or insidiously, at the onset of aura or headache, lasting for 2-48 hours, and ending abruptly. These episodes were stereotypic, characterized by disorientation with agitation, and retrograde amnesia for the episodes. Patients reported disorientation to time and place, inability to recognize friends and relatives, difficulty with finding directions home, fear of getting lost, inability to analyze traffic lights or tell time. Patients reliably predicted the episodes and felt the need to seek a safe place for protection. Severity of the episodes progressed, but a striking improvement occurred after the first stroke.
Conclusion.— ACM may be a presenting feature and important clue, enabling CADASIL to be recognized up to a decade or earlier than at present. Therefore, a brain MRI and/or testing for Notch3 mutations should be considered in adult patients with ACM.     

Sumatriptan in the Acute Treatment of Migraine Without Aura: Efficacy of 50-mg Dose

We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.     

Tolfenamic Acid Rapid Release Versus Sumatriptan in the Acute Treatment of Migraine: Comparable Effect in a Double-Blind, Randomized, Controlled, Parallel-Group Study

The efficacy and safety of tolfenamic acid and oral sumatriptan in the acute treatment of migraine was studied at five neurological centers in Finland. One hundred forty-one patients experiencing 289 migraine attacks, fulfilling the diagnostic criteria for migraine with or without aura as defined by the International Headache Society, were randomized.
For first attacks, 77% of patients receiving tolfenamic acid experienced a reduction of the initial severe or moderate headache to mild or no headache after 2 hours, as compared to 79% in the sumatriptan group and 29% in the placebo group. No significant difference was found between active treatments ( P =0.85, 95% Cl [−22%, 18%]), however, both active treatments were significantly better than placebo; P =0.001, 95% Cl (26%, 69%) for tolfenamic acid and P =0.001, 95% Cl (28%, 71%) for sumatriptan. For second attacks, results were similar with 70% of patients receiving tolfenamic acid experiencing relief, as compared to 64% in the sumatriptan group and 39% in the placebo group.
No significant differences were observed in accompanying symptoms.
Both drugs were well tolerated with the frequency of adverse events; 30% for tolfenamic acid and 41% for sumatriptan, a nonsignificant difference.
In this study, tolfenamic acid and oral sumatriptan are comparably effective in the acute treatment of migraine. When comparably effective, factors like individual effect, tolerance, and cost of treatment should be considered when prescribing migraine medication.     

Prochlorperazine—Treatment for Acute Confusional Migraine

Acute confusional migraine is a rare migraine variant primarily seen in childhood that lacks standardized diagnostic criteria. Acute symptomatic treatment for this disorder has not been established. We report 2 patients having a total of 6 episodes of acute confusional migraine where the symptoms resolved with prochlorperazine with variable success. Intravenous prochlorperazine was highly effective in 3 out of 4 episodes.     

Acute Treatment of Intractable Migraine With Sphenopalatine Ganglion Electrical Stimulation

Background.— We report preliminary results of a novel acute treatment for intractable migraine. The sphenopalatine ganglion (SPG) has sensorimotor and autonomic components and is involved in migraine pathophysiology.
Methods.— In 11 patients with medically refractory migraine, the sphenopalatine fossa was accessed with a 20-gauge needle using the standard infrazygomatic transcoronoid approach under fluoroscopy. Patients underwent temporary unilateral electric stimulation of the SPG with a Medtronic 3057 test stimulation lead after induction of full-blown migraine. Both sham and active stimulations with different settings were carried out for ≤60 minutes, and then the lead was removed.
Results.— In 11 evaluations, 2 patients were pain-free within 3 minutes of stimulation. Three had pain reduction; 5 had no response; 1 was not stimulated. Five patients had no pain relief. Stimulation settings: mean amplitude of 1.2V, mean pulse rate of 67 Hz, mean pulse width of 462 µs. Lack of headache relief appeared linked to suboptimal lead placement, poor physiologic sensory response to localization stimulation, and diagnosis of medication overuse headache.
Conclusion.— This study suggests a possible role for SPG stimulation in the treatment of refractory migraine headaches.