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

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

Opioids in Headache

Opioid analgesics have long been used to treat head pain of various types. This has been increasing to a significant degree over the past 25 years because of a trend for more liberal use of opioids in non‐malignant pain. Opioid treatment for acute headache, as well as prophylactically for refractory chronic headache, is controversial. There are a number of adverse effects associated with acute and chronic opioid treatment. Tolerance, dependence, and addiction are prominent issues. This article attempts to analyze the benefits and disadvantages for opioids in the management of migraine and other headache disorders, relying on known properties of this class of medication as well as clinical data. It will mainly focus on 2 topics: the use of opioid medication for the acute treatment of migraine attacks and continuous prophylactic use for refractory chronic migraine.     

Treating early versus treating mild: timing of migraine prescription medications among patients with diagnosed migraine

INTRODUCTION: Although research suggests that early treatment of migraine headache when the pain is mild results in better outcomes for patients, many patients delay taking their acute-migraine medication until their headaches are moderate or severe. Understanding when and why patients use their migraine medications is an important first step to improve migraine management. METHODS: A prospective observational study, conducted at a major national retail pharmacy chain with stores across the United States between April 2001 and November 2002, enrolled men and women between 18 and 55 years of age with a physician diagnosis of migraine with or without aura. Baseline data on 690 patients included patient demographics, migraine history, medication use, tendency to avoid or delay treatment of a migraine attack, and reasons for delaying treatment. Reasons for delaying treatment were assessed via a checklist of nine potential reasons. In the follow-up survey completed after treatment of the next migraine attack, patients reported the timing of medication use in relation to pain onset and the severity of the migraine headache at the time they took the medication. RESULTS: Despite the severity of their typical migraine attacks, approximately 49% of the respondents answered, "yes" to the question, "Do you often avoid or delay taking your migraine medications when you start to experience a migraine attack?" The two most common rationales for avoiding or delaying treatment were "wanting to wait and see if it is really a migraine attack" (69%) followed by "only want to take medications if it is a severe attack" (46%). In the follow-up survey, regardless of medication used, about 85% of patients did not treat their next migraine attack until the headache pain was moderate or severe, although 74% treated within 1 hour of pain onset. CONCLUSION: These results suggest that patients with migraine often delay their treatment until they have identified their attack as a migraine. In addition, while many patients treated their follow-up headache early, they did not treat when the pain was mild. This suggests that there is an opportunity for physicians to educate their migraine patients on how to differentiate migraine from other headache types and about when and how to use their acute-migraine medication.     

Is migraine a neuropathic pain syndrome?

The understanding of migraine pathophysiology has evolved from the belief that migraine is a vascular disorder, to evidence that better defines migraine as a neurogenic disorder associated with secondary changes in brain perfusion. There is evidence to suggest that the early phase of migraine pain results from neurogenic infiammation affecting cranial blood vessels and dura. Allodynia, hyperalgesia, and expansion of nociceptive fields occur during most well-established migraine attacks. These clinical features of migraine are evocative of those traditionally associated with neuropathic pain. A hypothesis that defines migraine pain as a unique neuropathic pain disorder can imply the potential for neural plasticity and may provide insight into the mechanisms that underlie the transformation of episodic to chronic forms of migraine. The neuropathic pain model of migraine pathophysiology not only paves the way for mechanism-based treatment strategies that can improve the acute and preventive management of migraine attacks, but also opens the door for the discovery of novel therapeutic targets. It also lends momentum to an understanding of clinically intriguing topics such as opiate-induced hyperalgesia and medication-overuse headache (rebound headache), opioid resistance in the treatment of chronic headache, and disease modification in defending against the potential for migraine transformation.     

Intranasal civamide for the acute treatment of migraine headache

The objective of this study was to investigate the safety and efficacy of intranasal civamide for the acute treatment of migraine headache with or without aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the neurones of the trigeminal plexus of their neurotransmitter content. Applied intranasally, the release of neurotransmitters to meningeal and dural blood vessels should be decreased, along with the resultant vasodilatation, plasma extravasation, and histamine/serotonin release. Subsequent migraine headache pain may also be diminished. Thirty-four patients were enrolled into a double-blind study of intranasal civamide, and randomized to receive a single dose of either 20 microg or 150 microg of civamide, for the treatment of a single migraine headache, with or without aura, of moderate to severe pain. At 2 h post-dose, 55.6% of patients treated with either dose had a decrease in pain severity, with 22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated with either dose had a decrease in pain severity, with 33.0% of patients being pain-free. Adverse events were similar for both dosages, with 91.2% of patients experiencing nasal burning and 44.1% of patients experiencing lacrimation. No systemic side-effects were observed. Based upon the results of this study, intranasal civamide may be effective in the acute treatment of migraine headache. Given civamide's proposed mechanism of action, intranasal civamide should be substantially more effective for prophylaxis than acute treatment of migraine. A study evaluating its efficacy in prophylaxis of migraine is currently planned.     

Monitoring of Acute Migraine Attacks: Placebo Response and Safety Data

In the course of evaluating the safety and efficacy of an investigational compound for acute migraine headaches, a large number of patients received placebo at a single site, offering the opportunity to characterize subjective and clinical physiologic responses of migraine patients to placebo in a controlled environment. In a single-site, double-blind, placebo-controlled study, 67 patients reported to the clinic while suffering a moderate to severe acute migraine headache and received oral placebo. For 6 hours after treatment, a continuous electrocardiogram (ECG) was performed, and headache severity, adverse events, and vital signs were recorded. Patients returned and repeated the procedure when free from pain. A headache was considered to be improved if its severity dropped to "mild" or "none." Twenty-five patients (37%; 95% Cl: 26% to 50%) experienced headache improvement within 2 hours of receiving placebo, and 32 patients (48%: 36% to 60%) improved within 4 hours. There were no clinically important ECG changes during the migraine visit, and there were no clinically relevant differences in vital signs between the migraine and pain-free visits. Thus, a substantial placebo response occurs in migraine headache. Hemodynamic and ECG parameters are unchanged between migraine and pain-free states.     

Aspirin is efficacious for the treatment of acute migraine

BACKGROUND: More than 50% of migraine sufferers rely on over-the-counter medications for the treatment of migraine. Along with other over-the-counter products, aspirin is considered by the US Headache Consortium to be an option for first-line migraine treatment. This study assessed the efficacy and tolerability of aspirin versus placebo for the acute treatment of a single acute attack of migraine. METHODS: This prospective, randomized, double-blind, parallel-group, placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of aspirin for the treatment of acute moderate to severe migraine, with or without aura. Subjects recorded all study evaluations in a diary at baseline and at .5, 1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point ordinal scale from no pain to severe pain. The primary efficacy end point was headache response at 2 hours. Secondary efficacy parameters included reduction of nausea, photophobia and phonophobia, pain intensity difference, and headache recurrence at 24 hours. RESULTS: Of 485 subjects enrolled, 409 took study medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 with placebo). Baseline demographic and migraine characteristics were not significantly different between groups. The 2-hour headache response rate was 52% with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) and continuing throughout the 6-hour evaluation period. Significantly (P<.05), more subjects were pain free from the 1-hour evaluation through the 6-hour evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68 subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24 hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well tolerated, and adverse events were not significantly different between groups. CONCLUSIONS: This study demonstrates that aspirin is safe and effective for treatment of acute migraine in appropriately selected patients.     

Results of a patient survey for an implantable neurostimulator to treat migraine headaches

Migraine attacks are believed to involve activation of the trigeminovascular system and trigeminal-parasympathetic reflex, which is mediated through the sphenopalatine ganglion (SPG). An implantable SPG neurostimulator has been developed to apply on-demand SPG stimulation for the treatment of severe primary headache. The neurostimulator is implanted via an oral incision and placed along the maxilla, with the lead placed at the SPG. The neurostimulator contains no battery and is powered and controlled via a handheld remote controller. The potential interest of patients with high-frequency, high-disability migraine in having a SPG neurostimulator implanted to treat migraine is unknown. We aimed to evaluate patient interest to undergo such an implantation procedure and to participate in a clinical investigation of on-demand SPG stimulation for migraine by conducting a survey at the Ghent University Hospital in 41 migraineurs. Seventy-seven percent (77%) of subjects expressed an interest in participating in a clinical investigation requiring implantation of a SPG neurostimulator when headache frequency and severity were considered and 69% when pain relief experienced with current migraine treatment was considered. Preventive and acute medications were used in 64 and 95% of the subjects, respectively, and provided a reported reduction of headache frequency, duration and pain. However, acute medications were frequently associated with headache recurrence and bothersome side effects. Results indicate that a majority of high-frequency, high-disability migraineurs, many of whom achieve pain relief with their current medications, have an interest in participating in a clinical investigation of an implantable SPG neurostimulator for the treatment of migraine headache.     

Chest Pain A Manifestation of Migraine

Background

Chest pain is an alarming symptom; it justifies many visits to the emergency department (ED). The etiology is often unknown. Chest wall pain in the presence of migraine headache, although not a common occurrence, is intriguing when it resolves with antimigraine treatment.

Objectives

To characterize the manifestations and outcomes and investigate the relationship between chest wall pain and headache as a manifestation of migraine exacerbation.

Methods

Among patients visiting our ED, we identified those individuals whose pain originated in the chest wall in the setting of migraine exacerbation. Patients with clinical indications for specific treatments were dispositioned accordingly. Control of symptoms including chest pain and headache with antimigraine agents was considered the primary outcome. A prospective follow-up via telephone interview and medical records review was performed.

Results

We collected a convenience sample of 33 patients. All manifested migraine headache with an earlier onset than the chest pain, and all had taken medications prior to visiting the ED. Twelve patients reported a higher visual analog scale score for the headache than for the chest pain. Still, chest pain was the main complaint. The chest pain originated at the chest wall. Ten patients received sublingual nitroglycerin or opiates, or both; no pain relief was reported. However, all symptoms resolved with metoclopramide. On follow-up, 6 patients reported recurrence of chest pain with subsequent migraines.

Conclusions

Chest pain can be a complication of migraine. The treatment should be focused on migraine control. Migraine should be included in the differential diagnosis of chest pain.     

Meeting patient expectations in migraine treatment: what are the key endpoints?

Clinical outcomes of migraine treatment are generally based on two major endpoints: acute pain resolution and effects on quality of life (QOL). Resolution of acute pain can be evaluated in a number of ways, each increasingly challenging to achieve; pain relief, pain freedom at 2 h, sustained pain-freedom, and SPF plus no adverse events (SNAE, the most challenging). QOL questionnaires help assess the burden of migraine and identify optimal treatments. Pain resolution and improved QOL form the basis of the ultimate target-meeting patient expectations, to achieve patient satisfaction. To achieve this, it is crucial to choose appropriate endpoints that reflect realistic treatment goals for individual patients. Moreover, SNAE can help discriminate between triptans, with almotriptan having the highest SNAE score. Kaplan-Meier plots are also relevant when evaluating migraine treatments. The use of symptomatic medication may lead to the paradoxical development of medication-overuse headache. In general practice, patients should use simple tools for pain measurement (e.g. headache diary) and a QOL questionnaire. A composite endpoint of pain resolution and QOL restoration would constitute a step forward in migraine management.     

Review of clinical trials using early acute intervention with oral triptans for migraine management

Most of the data on triptan use are from clinical trials in which patients were instructed to wait until migraine headache pain was moderate/severe in intensity. In the real world, patients may hesitate to use a triptan until headache pain is moderate/severe because of the cost of these agents or limited supply allowed by their health service organisation. However, accumulating data indicate that early intervention with an oral triptan when headache pain is still mild may be the most effective acute treatment strategy. Economic analyses also support early triptan intervention in migraine attacks. Tolerability is expected to be particularly important in early intervention, as patients treating mild migraine pain may be more reluctant to risk adverse events. Thus, an agent selected for use as early intervention should have both a demonstrated efficacy in treating mild migraine headache and placebo-like tolerability. This article reviews retrospective and prospective clinical trials which investigated the use of triptans for early acute migraine therapy.     

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

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

fficacy, Safety, and Tolerability of Dihydroergotamine Nasal Spray as Monotherapy in the Treatment of Acute Migraine

Recently, a new nasal spray formulation of dihydroergotamine was developed which facilitates at-home treatment of migraine. We studied the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the acute treatment of classic and common migraine in two, identical, double-blind, randomized, placebo-controlled trials. Of the 229 patients enrolled, 206 (102 dihydroergotamine nasal spray, 104 placebo) were included in the intent-to-treat analyses; 182 treated two headaches and 24 treated one headache. Based on both the patients' and physicians' ratings, dihydroergotamine nasal spray was significantly superior to placebo for reducing the severity of headache pain in both studies, and in relieving nausea in Study 2. The onset of significant efficacy with dihydroergotamine nasal spray compared to that with placebo for both severity of headache pain and relief of nausea occurred at I hour in Study 2 and at 3 hours in Study 1. Dihydroergotamine nasal spray was also significantly superior to placebo for the relief of headache pain in both studies. Based on the physicians' global evaluations of treatment efficacy for headache pain, 71% of the dihydroergotamine-treated patients in Study 2 and 59% of their counterparts in Study 1 were considered to be responders. The dihydroergotamine-treated patients had less newly-occurring vomiting than the placebo-treated patients. The majority of adverse events reported by the dihydroergotamine-treated patients were nasopharyngeal. The results demonstrate the efficacy, safety, and tolerability of dihydroergotamine nasal spray as monotherapy in the treatment of acute migraine attacks.     

A prospective double-blind study of nasal sumatriptan versus IV ketorolac in migraine

We conducted a study to compare the efficacy in migraine headache of nasal sumatriptan and intravenous ketorolac. The study was a prospective, double-blind study done with a convenience sample of 29 patients presenting to the emergency department (ED) with acute migraine. Patients received either 20 mg of nasal sumatriptan or 30 mg of intravenous ketorolac. Patients scored the severity of their headache on a 100-mm visual analog scale (VAS) of pain prior to medication, and again 1 hour after medication. Differences between initial and 1-hour scores were analyzed. Before treatment, no difference existed between the groups in the intensity of headache. One hour after medication, the sumatriptan group had a decrease in pain score of 22.937 mm and the ketorolac group a decrease of 71.462 mm on the VAS. The decrease in pain score with ketorolac was significantly greater than that with sumatriptan (P < 0.001). The study therefore showed that both sumatriptan and ketorolac effectively reduced the pain associated with acute migraine headache, but that intravenous ketorolac produced a greater reduction in pain than did nasal sumatriptan.     

Meta‐Analysis of the Efficacy and Safety of Naproxen Sodium in the Acute Treatment of Migraine

(Headache 2010;50:808‐818) Objective.— To assess the efficacy and safety of naproxen sodium in the treatment of acute migraine attacks. Background.— Non‐steroidal anti‐inflammatory drugs including naproxen sodium have been used in treating migraine attack. A number of clinical trials of naproxen sodium in migraine have been reported. However, it remains to be established whether naproxen sodium unequivocally offers clinical benefits taken into account the desired outcomes in acute migraine therapy as recommended by the International Headache Society. Methods.— Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM review, and the Cochrane Library) up to June 2009 and historical searches of relevant articles. Studies were included in the meta‐analysis if they were (1) double‐blind, randomized, placebo‐controlled trials that evaluated naproxen sodium tablet in moderate or severe migraine attacks in adult patients, and (2) reporting the efficacy in terms of headache relief, pain‐free, relief of migraine‐associated symptoms, sustained headache relief, sustained pain‐free, or headache recurrence. Data extraction and study quality assessment were performed independently by 2 investigators. Disagreements were resolved by a third investigator. Treatment effects and adverse effects were expressed as risk ratio. A random effects model was used when significant heterogeneity existed, otherwise the fixed effects model was performed. Results.— We identified 16 published randomized controlled trials of naproxen in the treatment of migraine. Four trials met the inclusion criteria and were included in the meta‐analysis. Naproxen sodium was more effective than placebo in reducing pain intensity and providing pain‐free within 2 hours in adults with moderate or severe migraine attacks. The pooled risk ratios were 1.58 (95% confidence interval [CI] 1.41‐1.77, P < .00001), and 2.22 (95% CI 1.46‐3.37, P = .0002), respectively, for headache relief at 2 hours and pain‐free at 2 hours. It was also effective in achieving headache relief at 4 hours, relief of migraine‐associated symptoms, sustained headache relief, and sustained pain‐free responses. There was no significant difference in headache recurrence rate between naproxen sodium and placebo. The risk of any adverse event was greater with naproxen sodium than with placebo (pooled risk ratio 1.29, 95% CI 1.04‐1.60, P = .02). The adverse events commonly associated with naproxen sodium were nausea, dizziness, dyspepsia, and abdominal pain. Conclusions.— The available evidence suggests that naproxen sodium is more effective but may cause more adverse events than placebo in the acute treatment of moderate to severe migraine. It is effective in reducing headache intensity, rendering pain‐free at 2 hours and improving migraine‐associated symptoms. However, its effectiveness relative to other active comparators needs to be better defined by appropriate head‐to‐head clinical trials.     

Acute treatment of headache

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.     

Personality Factors in Classical Migraine and Tension Headache

SYNOPSIS
The hypothesis that classical migraine and tension headache sufferers show a "specific headache personality" characterized by traits of obsessionality, neuroticism and repressed hostility was tested. A sample of fifteen classical migraine and fifteen tension headache sufferers selected without reference to treatment, was compared with fifteen non-headache normal subjects and fifteen subjects suffering physical pain but of a non-headache nature.
Personality tests of obsessionality, neuroticism, anxiety and hostility were administered. Analyses of variance revealed that sufferers from headache and non-headache physical pain had higher levels of neuroticism and repressed hostility than the non-headache controls. No evidence for increased incidence of obsessionality was found in any group.
It was concluded that the similarities between headache and non-headache physical pain sufferers found on several of the personality indices suggested that traits frequently reported as characteristic of headache sufferers may be the result of a coping strategy for recurrent pain and not specific to headaches.     

Rescue therapy for acute migraine, part 1: triptans, dihydroergotamine, and magnesium

Objective.— To review and analyze published reports on the acute treatment of migraine headache with triptans, dihydroergotamine (DHE), and magnesium in emergency department, urgent care, and headache clinic settings. Methods.— MEDLINE was searched using the terms “migraine” and “emergency,” and “therapy” or “treatment.” Reports from emergency department and urgent care settings that involved all routes of medication delivery were included. Reports from headache clinic settings were included only if medications were delivered by a parenteral route. Results.— Acute rescue treatment studies involving the triptans were available for injectable and nasal sumatriptan, as well as rizatriptan. Effectiveness varied widely, even when the pain‐free and pain‐relief statistics were evaluated separately. As these medications are known to work best early in the migraine, part of this variability may be attributed to the timing of triptan administration. Multiple studies compared triptans with anti‐emetics, dopamine antagonists, and non‐steroidal anti‐inflammatory drugs. The overall percentage of patients with pain relief after taking sumatriptan was roughly equivalent to that recorded with droperidol and prochlorperazine. Sumatriptan was equivalent to DHE when only paired comparisons were performed. While the data extracted suggest that magnesium may be effective in treating all symptoms in patients experiencing migraine with aura across all migraine patients, its effectiveness seems to be limited to treating only photophobia and phonophobia. Conclusions.— Although there are relatively few studies involving health‐care provider‐administered triptans or DHE for acute rescue, they appear to be equivalent to the dopamine antagonists for migraine pain relief. The relatively rare inclusion of a placebo arm and the frequent use of combination medications in active treatment arms complicate the comparison of single agents with each other.