Repetitive Intravenous DHE in the Treatment of Refractory Headache

We analyzed retrospectively the data for 300 patients with refractory headache who were treated with dihydroergotamine (DHE) at the Comprehensive Headache Center at Germantown Hospital. The patients had either chronic daily headache (with drug rebound -216, without rebound -42), short-duration headache (18), or cluster headache (24). Treatment consisted of withdrawal of overused medications (usually analgesics and ergots), repetitive IV administration of DHE, and use of metoclopramide and prophylactic medications, together with educational and psychological support. Overall, 91% (range, 86% to 100%) of the patients became headache-free, usually within 2 to 3 days. The average duration of hospitalization was 7.4 days. Side effects, reported in 157 (52%) of the patients, consisted primarily of nausea (32%), tightness and burning (8%), leg cramps (7%), vomiting (6%), and increased blood pressure (5%). The side effects generally resolved spontaneously or with adjustment of the DHE dose and/or adjunct medication, and necessitated withdrawal of therapy in only 2 patients (1 with drug-related claudication; 1 with somatic complaints of uncertain origin). We conclude that a regimen of repetitive intravenous DHE and metoclopramide can provide rapid relief of chronic intractable headache, and can ameliorate the effects of analgesic and ergot withdrawal in patients with chronic daily headache and rebound associated with overuse of these drugs.     

A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal spray in the acute treatment of migraine

A multinational, multicentre, randomised, double-blind, double-dummy, crossover study (368 patients treating two attacks) was conducted to compare the efficacy and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60 minutes after dosing, significantly more patients obtained headache relief (change from moderate or severe to none or mild) after treatment with sumatriptan than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients reported relief of nausea after sumatriptan than after DHE at 60 minutes (64% sumatriptan, 49% DHE, p = 0.006). A significant difference between the two treatments was first observed at 45 minutes with respect to both headache relief (38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40% DHE, p = 0.014). There were no significant differences between the two treatments for other measures of efficacy. Both treatments were well tolerated, with only 10% of patients in each group reporting one or more adverse events. The most frequently reported adverse event after sumatriptan was a bad or bitter taste, which was reported by 5% of patients. After DHE, 4% of patients reported symptoms of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse events. It is concluded that sumatriptan nasal spray is superior to DHE nasal spray in the relief of pain and nausea associated with acute migraine headache.     

Use of Dihydroergotamine in Patients with Postconcussion Syndrome

SYNOPSIS
The experience with 34 patients who came to the Shreveport Headache Clinic for treatment of postconcussion headache is reviewed. All had been suffering from postconcussion (posttraumatic) syndrome for periods ranging from one day to more than three years, and all displayed, in addition to headache, at least three other symptoms characteristic of the syndrome, eg, memory problems, impaired concentration, sleep problems, dizziness, and anxiety. After initial evaluation at the clinic, the patients were admitted to Willis Knighton Medical Center and treated with repetitive administration of intravenous dihydroergotamine (DHE) and metoclopramide. A good to excellent overall response to DHE therapy was achieved by 88% (29) of the patients. The percentages and numbers of patients obtaining good to excellent relief of selected key symptoms were: 85% (28) - headache, 91% (30) - memory problems, 94% (31) - sleep problems, and 88% (29) - dizziness. DHE was well-tolerated, and no serious or unexpected adverse reactions were reported. The most frequently reported adverse reactions were mild nausea and brief worsening of headache.     

Rate of metoclopramide infusion affects the severity and incidence of akathisia

Objective: To investigate the effect of the rate of metoclopramide infusion on akathisia incidence, severity, onset of symptoms, and duration in patients with headache, and/or nausea/vomiting in the emergency department (ED) setting. Methods: Prospective, double blind, randomised clinical study comparing two rates of intravenous infusion of metoclopramide over a period of six months at a tertiary university hospital ED. Results: A total of 300 patients presented to the ED met the inclusion criteria: 151 (50.3%) with nausea/vomiting, 108 (36%) with headache, and 41 (13.7%) with headache and nausea/vomiting. Of these, 154 patients (51.3%) were given 10 mg metoclopramide as a slow intravenous infusion over 15 minutes plus placebo (SIG group) and 146 patients were given 10 mg metoclopramide intravenous bolus infusion over two minutes plus placebo (BIG group). Nine of the 154 patients in the SIG group (5.8%) had akathisia compared with 36/146 patients (24.7%) in the BIG group (p<0.001, OR 5.273, 95% CI 2.43 to 11.403). Severe akathisia were observed in 13/45 (28.8%). The incidence of severe akathisia was significantly higher in the BIG group (30.5%; 11/36) than in the SIG group (22.2%; 2/9), p = 0.009. Metoclopramide successfully relieved the presenting symptom(s) of 137/146 (90.8%) and 139/154 (90.2%) patients in the BIG and SIG groups, respectively. Conclusions: This study suggests that slowing the rate of infusion of metoclopramide is an effective strategy for reducing the incidence of akathisia in patients with headache, and/or nausea/vomiting in ED.     

Rescue therapy for acute migraine, part 3: opioids, NSAIDs, steroids, and post-discharge medications

Objective.— The final section of this 3‐part review analyzes published reports involving the acute treatment of migraine with opioids, non‐steroidal anti‐inflammatory drugs (NSAIDs), and steroids in the emergency department (ED), urgent care, and headache clinic settings, as well as post‐discharge medications. In the Conclusion, there is a general discussion of all the therapies presented in the 3 sections. Method.— Using the terms (“migraine” AND “emergency”) AND (“therapy” OR “treatment”), the author searched MEDLINE for reports from ED and urgent care settings that involved all routes of medication delivery. Reports from headache clinic settings were included only if medications were delivered by a parenteral route. Results.— Seventy‐five reports were identified that compared the efficacy and safety of multiple acute migraine medications for rescue. Of the medications reviewed in Part 3, opioids, NSAIDs, and steroids all demonstrated some effectiveness. When used alone, nalbuphine and metamizole were superior to placebo. NSAIDs were inferior to the combination of metoclopramide and diphenhydramine. Meperidine was arguably equivalent when compared with ketorolac and dihydroergotamine (DHE) but was inferior to chlorpromazine and equivalent to the other dopamine antagonists. Steroids afford some protection against headache recurrence after the patient leaves the treatment center. Conclusions.— All 3 opioids most frequently studied – meperidine, tramadol, and nalbuphine – were superior to placebo in relieving migraine pain, although meperidine combined with promethazine was not. Opioid side effects included dizziness, sedation, and nausea. With ketorolac being the most frequently studied drug in the class, NSAIDs were generally well tolerated, and they may provide benefit even when given late in the migraine attack. The rate of headache recurrence within 24‐72 hours after discharge from the ED can be greater than 50%. Corticosteroids can be useful in reducing headache recurrence after discharge. As discussed in Parts 1, 2, and 3, there are effective medications for provider‐administered “rescue” in all the classes discussed. Prochlorperazine and metoclopramide are the most frequently studied of the anti‐migraine medications in the emergent setting, and their effectiveness is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in migraine pain relief. Although there are fewer studies involving sumatriptan and DHE, relatively “migraine‐specific” medications, they appear to be equivalent to the dopamine antagonists for migraine pain relief. Lack of comparisons with placebo and the frequent use of combinations of medications in treatment arms complicate the comparison of single agents to one another. When used alone, prochlorperazine, promethazine, metoclopramide, nalbuphine, and metamizole were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also are more likely to produce side effects that are difficult for a patient to tolerate (especially akathisia). Metoclopramide was equivalent to prochlorperazine, and, when combined with diphenhydramine, was superior in efficacy to triptans and NSAIDs. Meperidine was arguably equivalent when compared with ketorolac and DHE but was inferior to chlorpromazine and equivalent to the other neuroleptics. Sumatriptan was inferior or equivalent to the neuroleptics and equivalent to DHE when only paired comparisons were considered. The overall percentage of patients with pain relief after taking sumatriptan was equivalent to that observed with droperidol or prochlorperazine. (Headache 2012;52:467‐482)     

A protocol for butalbital, aspirin and caffeine (BAC) detoxification in headache patients

The abuse of the combination drug containing butalbital 50 mg, aspirin 325 mg and caffeine 40 mg (or BAC), is commonly recognized by headache specialists as causing headaches. Despite this widespread problem, there is not a published treatment regimen for the BAC detoxification of patients. I describe such a protocol which was used four times in three patients. These patients fulfilled the diagnostic criteria of the IHS Headache Classification for headaches induced by chronic substance abuse (8.2) and analgesics abuse headache (8.2.2). These patients took between 150 and 420 BAC/month for 2-15 years. Two patients had previously undergone inpatient detoxification. One patient unsuccessfully tried detoxification twice as an outpatient. All patients were required to have psychological support prior to hospitalization for this protocol. BAC was discontinued. A pentobarbital challenge test corroborated butalbital dosage. The patients were given phenobarbital and caffeine which were tapered over several days. Dihydroergotamine (DHE) with metoclopramide was used (Raskin). Propranolol 60 mg bid was started. No narcotics were permitted. After hospital discharge, patients were allowed to continue subcutaneous DHE, as needed. One patient restarted BAC use after 8 months without it. The other two patients were still BAC free 18 and 14 months after detoxification.     

Treatment of Childhood Headache with Dihydroergotamine Mesylate

SYNOPSIS
This study was undertaken to determine whether pediatric patients with migraine without aura who have failed standard outpatient regimens including intravenous dihydroergotamine mesylate (DHE) in conjunction with oral metoclopramide would respond to an inpatient treatment protocol of intravenous DHE and oral metoclopramide. Thirty patients were evaluated in this study which was an open label, retrospective review of treatment. Independent of the duration of the refractory migraine, 80% of the patients responded to the protocol with only minimal side effect. The dose of DHE mesylate ranged from 0.1 to 0.5 mg. The dose of DHE is lower than is typically utilized in standard adult protocols. The patients received an average of five doses of DHE.     

Clinical Experience With Patient Administered Subcutaneous Dihydroergotamine Mesylate in Refractory Headaches

This study examines the practicality and efficacy of dihydroergotamine mesylate (DHE) when self-administered subcutaneously in a population of refractory headache patients. Forty-three patients with chronic daily headache or migraine headache without aura, who had been taught self-injection of DHE either through the Raskin Protocol or in an outpatient headache clinic, were contacted by telephone and administered a questionnaire regarding usage and results from DHE injection. Ninety-two percent of patients could successfully administer DHE. Forty-six percent of patients experienced 90% or greater relief of pain and the majority of patients (77%) had greater than 50% relief. Emergency room use was decreased in 83% and 80% preferred DHE to their previous therapy. While side effects were common (79%), only four patients (9%) stopped DHE for this reason. No convincing evidence for the development of rebound headaches due to DHE was found in this sample.     

Dihydroergotamine nasal spray in the treatment of attacks of cluster headache

A double-blind trial of dihydroergotamine (DHE) nasal spray compared with placebo was carried out in patients with cluster headache. Twenty-five patients were included in the trial. In three patients, all receiving DHE, the pain attacks ceased after five attacks. In the other 22 patients, 133 attacks were treated with placebo and 137 attacks with DHE nasal spray (dosage, 1 mg of DHE). The trial showed that the treatment given has no effect on the attack frequency or the duration of the single attack. However, the treatment had a significant effect on the intensity of the single attacks. It can be concluded that the trial should be repeated, using a larger dosage of DHE. This should be ethically justifiable, since none of the patients had any adverse reactions locally in the mucous membrane of the nose or systemically.     

Combined oral lysine acetylsalicylate and metoclopramide in the acute treatment of migraine: a multicentre double-blind placebo-controlled study

This multicentre, double-blind, randomized, placebo-controlled, parallel study was designed to evaluate the efficacy of combined oral lysine acetylsalicylate and metoclopramide (LAS-MCP) in the acute treatment of migraine attacks. A total of 266 patients, 18–65 years old, with two to six attacks of migraine with or without aura (IHS criteria) per month were included. The patients had to treat two migraine attacks with LAS-MCP (1620 mg lysine acetylsalicylate-the equivalent of 900 mg aspirin- combined with 10 mg metoclopramide) or placebo. The main outcome measure was headache relief (reduction in headache severity from grade 3 or 2-severe or moderate-to grade 1 or 0-mild or none) 2 h after treatment. LAS-MCP was superior to placebo for headache relief (56% vs 28%) and for the following secondary outcome measures: complete headache relief (18% vs 7%; p < 0.001), nausea (28% vs 44%; p < 0.001), vomiting (3% vs 11%; p = 0.001), use of rescue medication (47% vs 68%; p < 0.001), global efficacy judged as good or excellent (32% vs 14%; p < 0.001). The tolerability was considered as good in 94% of treated attacks in both groups. Combined oral lysine acetylsalicylate and metoclopramide is an effective and well-tolerated acute treatment of migraine attacks.     

Outpatient Repetitive Intravenous Dihydroergotamine

The efficacy of the repetitive intravenous dihydroergotamine (DHE) inpatient protocol for refractory headache is well established. We conducted a retrospective and prospective study of long-term headache patients at our clinic to evaluate this regimen in an outpatient setting. Treatment consisted of oral metoclopramide and four doses of DHE, with the total dose equaling 4 mg., administered over two days. Patients were followed for up to 10 weeks while they continued to receive prophylactic medication. Responsiveness was rated in terms of decreased frequency or severity of headache: excellent (75% to 100%), moderate (50-75%), mild (25-50%), and none (0-25%). In the retrospective study, 69% (43/62) of patients with chronic daily muscle-contraction-type headache and severe migraine had an excellent response at two days. An excellent or moderate response was sustained over three weeks in 65% (32/49) of the study group (13 patients were dropped from the study for failing to comply with record keeping requirements). At the 6- and 10-week follow-up evaluations, the majority of patients (76% and 70%, respectively) reported mild or no relief. Among patients with refractory daily headache or frequent severe migraine studied prospectively, 80% (28/35) reported an excellent response at two days. After six weeks, 66% (23/35) showed excellent or moderate relief. For both groups combined, 73% (71/97) of patients showed an excellent response to DHE at two days, with 43% (33/77) sustaining excellent or moderate relief at six weeks. Side effects, including nausea, leg cramps, facial flushing, increased blood pressure, diarrhea, burning at the injection site, and tightness in the throat and/or chest, were generally mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuous Intravenous Dihydroergotamine in the Treatment of Intractable Headache

We reviewed data on 171 patients with refractory headache treated by continuous intravenous dihydroergotamine mesylate (IV DHE 45 ÒÒ ) and repetitive IV DHE and compared the efficacy of continuous IV DHE to repetitive IV DHE. One hundred (58.5%) patients had refractory chronic daily headache. Seventy-one (42%) had drug rebound headache. One hundred thirty-eight (81%) had refractory migraine without aura, and 28 (16%) had migraine with aura. Treatment consisted of either continuous IV DHE by infusion pump or repetitive IV DHE and withdrawal of excessively used analgesics, analgesic narcotics, ergotamines, or benzodiazepines. Eighty-nine (92.5%) patients treated with continuous IV DHE became headache-free; the majority, 62 (64.5%), within 3 days. Sixty-five (86.5%) patients treated by repetitive IV DHE became headache-free, 50 (66.5%) within three days. The average hospital stay for both treatment groups was 4 days. Twelve (12.5%) of the continuous group and 12 (16%) of the repetitive group were headache-free within 24 hours. The average length of time to become headache-free was similar for the two groups, 3.06 days for continuous IV DHE and 2.94 days for repetitive IV DHE. The most common side effect was nausea, followed by diarrhea, vomiting, and leg cramps.
We conclude that DHE can be accurately and easily administered by continuous IV infusion pump, and that continuous IV DHE is a safe and efficacious mode of treatment producing results similar to repetitive IV DHE.     

Home Administration of Intramuscular DHE for the Treatment of Acute Migraine Headache

SYNOPSIS
Dihydroergotamine (DHE) has been used for the treatment of acute migraine headache for almost 50 years. Previous studies have emphasized use in emergency room, inpatient, or office settings. Twenty-nine patients with migraine headache who had failed to obtain relief with conventional therapy were trained to self-administer intramuscular DHE. The patients administered 0.5 mg DHE and 100 mg trimethobenzamide at the onset of their headache and an additional O.5mg DHE if satisfactory headache relief was not obtained. Twenty patients were successfully contacted and interviewed. Forty-five percent of the patients had at least 50% relief of headache and continued to use the protocol. Eighty-two percent of patients who initially had at least 50% headache relief continued to use the drug, whereas none of the patients who initially had less than 10% relief continued the protocol. Sixty-one percent of patients whose headaches precluded continuation of activity had at least 50% response to initial treatment, whereas only 29% whose headaches were less severe had this response. Initial response to therapy was predictive of continued use of the treatment protocol and patients who described more severe headache had a higher response to the initial treatment. Thus, home administration of I.M. DHE offers an additional treatment regimen for patients with migraine headache.     

Early and Transient Side Effects of Repetitive Intravenous Dihydroergotamine

Side effects associated with administration of repetitive intravenous dihydroergotamine (DHE) were prospectively studied in 72 patients with chronic daily headache who ware hospitalized in a dedicated inpatient headache treatment program. All patients received 11 consecutive doses of DHE, starting with 0.25 mg and increasing by 0.25 mg up to a maximum dose of 1.25 mg, depending on side effects and/or headache relief. The adverse events were recorded after each dose administered.
The great majority of patients (91.6%) reported at least one side effect. The most common were: nausea (72.2%), increase in previous headache (47.2%), lightheadedness (33.3%), "new" headache (27.8%), and leg cramps (23.6%). The overall number of side effect complaints did not increase proportionally with the strength of the dose of DHE administered. These complaints declined from the earlier to the later doses of DHE, except for leg cramps, which were more common with the later doses.
Side effects determined the strength of subsequent doses of DHE in only 18.1% of patients. Only four patients had to have a decrease in dosage and none required termination of DHE due to side effects.
Although repetitive intravenous DHE causes frequent side effects, they are usually mild and transient and decrease with subsequent doses, even at higher doses.     

Current Emergency Treatment of Severe Migraine Headaches

SYNOPSIS
Objective: To compare the efficacy of the combination of meperidine and hydroxyzine IM, versus dihydroergotamine and metoclopramide IV in the treatment of severe migraine headaches.
Design: This was a randomized double-blind, double-dummy study.
Setting: Established patients, whose headache had failed to respond to their usual abortive agent, were invited to an out-patient headache clinic for the study.
Patients: Twenty-eight patients, diagnosed as suffering from either migraine headache or chronic daily headache, were screened on arrival to exclude life-threatening causes.
Intervention: Group A (14 patients) received dihydroergotamine 1mg and metoclopramide 10mg IV and a placebo injection IM, and Group B (14 patients) received meperidine 75mg and hydroxyzine 75mg IM and a placebo injection IV.
Main Outcome Measures: Patients rated their headaches on a scale of 0-3 prior to treatment and again at 30 and 60 minutes.
Results: Both groups experienced improvement in headache severity. (Group A P=0.001 and Group B P=0.003). Improvement in pain scale score was greater for Group A than Group B, (P=0.006). The number of patients having s mild or no headache in Group A (13/14) was significantly greater than Group B (3/14). (P<0.001)
Conclusions: The combination of dihydroergotamine and metoclopramide IV should replace the standard IM narcotic and antiemetic as the parenteral treatment of choice for severe migraine headache.     

A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy

The potent serotonin receptor (5-HT₃) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (80 mg/m²) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P=0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P=0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.     

Ketorolac in Acute Headache Management

Twelve patients presenting to an emergency department in headache crisis were treated with Ketorolac tromethamine 60 mg. intramuscularly. All improved sufficiently to require no further emergent treatment. There was statistically significant improvement on all segments of the short form McGill Pain Questionnaire. This open label trial suggests that Ketorolac Tromethamine may be a useful agent in the treatment of headache crisis, and a controlled study to examine this is warranted.     

Superiority of methylprednisolone sodium succinate over low dose metoclopramide hydrochloride in the prevention of nausea and vomiting produced by cancer chemotherapy

Methylprednisolone sodium succinate and metoclopramide were compared for their efficacy, tolerance, and safety in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy in patients with cancer. Previously untreated patients about to receive at least 2 cycles of identical chemotherapy were entered into a study using a randomized, double-blind, crossover design. Patients were given either 250 mg of methylprednisolone or 10 mg of metoclopramide intravenously before the first cycle of chemotherapy and were then crossed over to receive the alternate medication before the second cycle of chemotherapy. Prochlorperazine was prescribed in both cycles for postchemotherapy nausea and vomiting. After each treatment cycle patients recorded the degree of nausea, drowsiness and anxiety, the number of episodes of vomiting experienced, and the amount of prochlorperazine taken. After the second treatment cycle patients recorded their preference for either the first or the second antiemetic medication with respect to nausea, vomiting, and overall effectiveness. Of 157 patients entered into the study, 115 were fully appraisable. Methylprednisolone was superior to metoclopramide in preventing nausea and vomiting and in decreasing anxiety and the amount of prochlorperazine used. A majority of the patients expressing a preference preferred methylprednisolone to metoclopramide for control of nausea (p = 0.003), control of vomiting (p = 0.0006), and overall effectiveness (p = 0.00004). There were few side-effects. We conclude that methylprednisolone may have some utility as an antiemetic in patients receiving moderately emetogenic chemotherapy, and who are treated as outpatients.     

A Controlled Study of Dihydroergotamine in the Treatment of Acute Migraine Headache

SYNOPSIS
A prospective, double-blind, crossover study was conducted of the effectiveness of dihydroergotamine (DHE) vs. placebo in the treatment of acute migraine in the emergency department. Thirty-seven patients were enrolled. By 60 minutes after treatment, those receiving DHE first had significantly better relief of pain than those receiving it later. Side effects were fairly common but were minor and did not necessitate terminating treatment. Eleven per cent of patients had significant relief of pain with prochlorperazine pre-treatment alone. Only 13.5% of patients treated with this DHE regimen required narcotics at the end of the study for relief of pain, compared to 45% of migraine headache patients seen concurrently in the same emergency department who were not enrolled in the study. We conclude that treatment with intravenous prochlorperazine and DHE is a safe and effective treatment and a useful alternative to narcotics.     

DHE in the pharmacotherapy of migraine: potential for a larger role

Despite a large array of currently marketed, frequently effective drugs for the acute treatment of migraine headache, comprising various classes and formulations, predictably reliable treatment for most headache types is often lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective therapy for migraine headache that could potentially be used for a broader range of headache types than occurs at present. The features of DHE supporting this assertion include (1) effectiveness in terminating severe, long-lasting headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, (4) minimal risk of medication-overuse headache, and (5) in the nasal spray formulation, suitability for outpatients (especially patients who are very nauseated or vomiting, potentially obviating the need for an office or hospital visit for acute care). Conditions or circumstances for which there are data supporting the expanded use of DHE include menstrual migraine, migraine with central sensitization and cutaneous allodynia, medication-overuse headache, migraine recurrence, and status migrainosus. The introduction of the intranasal formulation of DHE provides both pharmacologic and patient-convenience advantages for use in migraine therapy. This article reviews the rationale for the use of DHE in these common, often difficult-to-treat migraine forms.