Office-Based Treatment of Acute Migraine With Dihydroergotamine Mesylate

SYNOPSIS
The Regional Migraine Field Trial assessed the efficacy and safety of dihydroergotamine mesylate (D.H.E. 45 ^(r) ) for migraine in the office setting. Patients were admitted to the study provided they met the International Headache Society definition of migraine with or without aura. Thirty-eight neurologists enrolled 311 patients (274 women and 37 men) between the ages of 13 and 70 years in this open-design study. Ninety-five percent of the patients had moderate or severe headache pain at entry, and 62% had nausea. All patients received a single intramuscular injection of D.H.E. 45 ^(r) 1 mg. A second intramuscular injection of 1 mg was given 60 minutes after the first injection, if needed. An antiemetic was administered concomitantly with D.H.E. 45 ^(r) , if needed. Rescue therapy was given at the investigators' discretion. Efficacy was judged by the relief of pain, patients' ability to function, need for a second injection, need for rescue medication, and need for an antiemetic. At 30 and 60 minutes, 46% and 72% of patients had only mild or no head pain, respectively. At 24 hours, 77% of all patients had mild or no head pain. D.H.E. 45 ^(r) also improved functional ability. At 30 and 60 minutes, 58% and 75% of patients had only mild or no disability, respectively. At 24 hours, 81% had mild or no impairment. Nausea was present in 62% of patients at the outset, 40% of patients at 30 minutes, and 30% at 60 minutes. An antiemetic was given to 43% of patients at the outset. The presence of nausea was similar whether or not patients received an antiemetic. Rescue medication was needed for 11% of patients, and adverse events were reported by 9%. In conclusion, D.H.E. 45 ^(r) is effective therapy for acute migraine. A second dose provides additional relief, if needed.     

Temperature Biofeedback Treatment for Migraine Headache: A Controlled Multiple Baseline Study

SYNOPSIS
A multiple baseline, within subject, controlled design was used to examine the effectiveness of a temperature biofeedback procedure augmented with autogenic and relaxation training, in the treatment of four patients who met the criteria for the migraine syndrome. Before treatment was begun, each patient recorded baseline data on hourly ratings of headache intensity and amount of analgesic medication used. The treatment package consisted of: (1) instructions aimed at generating favorable therapeutic expectations; (2) modified relaxation training; (3) use of autogenic phrases; and, (4) fingertip temperature feedback. In accord with the multiple baseline design, this package was introduced to individual patients sequentially in such a way that the effect of treatment was observed in headache and medication records of one patient before treatment was introduced to the next patient.
Results indicated that the treatment package had an impact on ratings of headache intensity and medication usage. The data showed idiosyncratic variations and individual differences among subjects in the response to treatment.     

Subcutaneous Sumatriptan in the Acute Treatment of Migraine in Patients Using Dihydroergotamine as Prophylaxis

SYNOPSIS
The efficacy of sumatriptan, a 5-HT 1 receptor agonist, in patients with migraine attacks occurring despite prophylactic treatment with oral dihydroergotamine, was assessed in a double-blind placebo-controlled study involving 76 patients. Thirty-seven patients were treated with a subcutaneous injection of 6 mg sumatriptan self-administered with an auto-injector and 39 with placebo given by the same route. Patients having inadequate relief were allowed to use a second injection of test medication I hour later and rescue treatment between 2 hours and 24 hours after the first dose. Headache relief was achieved within 2 hours after sumatriptan in 26 patients (70%) compared to 8 patients (21%) in the placebo group (P<0.0001). Of these patients, 19 (51%) and 3 (8%) were, respectively, pain free at this time. A second injection of sumatriptan was used by 8 (22%) patients compared to 30 (77%) patients in the placebo group (P<0.0001), whereas rescue medication was used respectively by 13 (35%) and 22 (58%) patients (P < 0.024). The adverse event profile of sumatriptan was not affected by the concomitant use of dihydroergotamine and side-effects were all minor and transient. Patient satisfaction was significantly higher in the sumatriptan group (75%) compared to patient satisfaction with placebo (16%). These results show that the high efficacy rate of subcutaneous sumatriptan and its safety profile remain unchanged in migraine patients receiving oral dihydroergotamine as pro-phylaxis.     

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.     

Dihydroergotamine and Metoclopramide in the Treatment of Organic Headache

Dihydroergotamine and metoclopramide have been used in the treatment of benign headache for many years. The presumed mechanism of action of dihydroergotamine and metoclopramide is related to these drugs' affinity for serotonergic receptors. We present three cases of the use of dihydroergotamine and metoclopramide in patients with organic headache (two patients with viral meningitis and one patient with meningeal carcinomatosis). All three patients had excellent symptomatic relief. Our results demonstrate that dihydroergotamine and metoclopramide can be effective in treating organic headache and, therefore, symptomatic relief can not be assumed to signify benign disease.     

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.     

Prophylaxis of Migraine and Mixed Headache. A Randomized Controlled Study

SYNOPSIS
The three most commonly used modalities in the prophylactic treatment of headache, namely propranolol, amitriptyline and biofeedback training, were compared individually and in combination. Three hundred forty patients with migraine end 375 patients with mixed headache were randomly allotted to 8 therapeutic categories. The total duration of the study was 312 years and the therapeutic groups were evaluated for a period of 7 months including I month of pretreatment observation. Improvement was assessed by percentage of change in the average headache index during the last three months of evaluation from the pretreatment headache index. In the migraine group 273 patients completed the study. Improvement was significantly higher in patients receiving prophylactic treatment compared to control patients who were on abortive Ergotamine treatment. Propranolol plus biofeedback yielded the best results in the migraine group and addition of amitriptyline did not significantly change the percentage of improvement. Propranolol alone (62%) was significantly superior to amitriptyline (42%) (p < 0.01). The differences between propranolol alone and propranolol plus amitriptyline was not statistically significant.
In the mixed headache group 281 patients completed the study. The most effective treatment was combination of amitriptyline, propranolol and biofeedback training. Amitriptyline alone was superior to propranolol alone in the treatment of mixed headache (p<0.01). A combination of propranolol and amitriptyline was superior to either of those alone. Biofeedback, though by itself, did not appear to be the treatment of choice, significantly contributed to better results as an adjunct when it is combined with pharmacological agents. Concomitant use of propranolol and amitriptyline did not result in any adverse reactions or clinical incompatibility.     

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.     

Intranasal Lidocaine for the Treatment of Migraine Headache: A Randomized, Controlled Trial

OBJECTIVE: To evaluate the effect of intranasal lidocaine for immediate relief (5 minutes) of migraine headache pain. METHODS: A randomized, double-blind, placebo-controlled clinical trial at two university-affiliated community teaching hospitals enrolled patients 18-50 years old with migraine headache as defined by the International Headache Society. Patients who were pregnant, lactating, known to abuse alcohol or drugs, or allergic to one of the study drugs, those who used analgesics within two hours, or those with a first headache were excluded. Statistical significance was assessed by using chi-square or Fisher's exact test for categorical variables and Student's t-test for continuous variables. Patients rated their pain on a 10-centimeter visual analog scale (VAS) prior to drug administration and at 5, 10, 15, 20, and 30 minutes after the initial dose. Medication was either 1 mL of 4% lidocaine or normal saline (placebo) intranasally in split doses 2 minutes apart and intravenous prochlorperazine. Medications were packaged so physicians and patients were unaware of the contents. Successful pain relief was achieved if there was a 50% reduction in pain score or a score below 2.5 cm on the VAS. RESULTS: Twenty-seven patients received lidocaine and 22 placebo. No significant difference was observed between groups in initial pain scores, 8.4 (95% CI = 7.8 to 9.0) lidocaine and 8.6 (95% CI = 8.0 to 9.2) placebo (p = 0.75). Two of 27 patients (7.4%, 95% CI = 0.8, 24.3) in the lidocaine group and three of 22 patients (13.6%, 95% CI = 2.8 to 34.9) in the placebo group had immediate successful pain relief (p = 0.47), with average pain scores of 6.9 (95% CI = 5.9 to 7.8) and 7.0 (95% CI = 5.8 to 8.2), respectively. No difference in pain relief was detected at subsequent measurements. CONCLUSION: There was no evidence that intranasal lidocaine provided rapid relief for migraine headache pain in the emergency department setting.     

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.     

The Treatment of Cluster Headache With Repetitive Intravenous Dihydroergotamine

We reviewed our experience with 54 cluster headache patients (23 episodic, 31 chronic) admitted to our headache center 64 tines over the past five years and treated with repetitive intravenous dihydroergotamine (IV DHE). DHE therapy was initiated on admission and prophylactic medication regimens were started or adjusted. All 54 patients had complete relief of their cluster headache, usually within two days. Most (82.8%) had no side effects. The average length of hospitalization was 6.7 days. At the three month followup, 92.9% of the episodic cluster patients were headache-free and 7.1% had a 50-74% improvement; at six months, all were headache-free. Of the chronic cluster patients, 44.4% were headache-free at three months and 52.8% had at least 50% improvement. At six months, 75% were headache-free and 22.2% were at least 75% improved, probably as a result of continued prophylactic medication. Repetitive IV DHE safely, rapidly, and effectively controls cluster headache.     

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.     

Controlled Trials of Cimetidine in Migraine and Cluster Headache

SYNOPSIS
Controlled double-blind trials of the histamine H₂-receptor antagonist, cimetidine, alone and in combination with the histamine H₁-receptor antagonist, chlorpheniramine, in 24 patients with migraine and 20 patients with cluster headache, showed that these agents were ineffective in prophylaxis. The reason for this may lie in the fact that induced intracellular histamine does not act via receptors and does not necessarily negate the hypothesis that histamine plays a role in the pathogenesis of vascular headaches.     

Practice and Economics Cost Considerations in Headache Treatment Part 2: Acute Migraine Treatment

Today's physician has many useful medication options available for acute migraine treatment. There is a wide cost range among these drugs and today's health care environment demands that cost be factored into the decision process. Effective migraine abortive treatment decreases the costs of repeat dosing and disability. Early use of migraine abortive medication can increase its rapidity of action and effectiveness. Adjunctive medication such as metoclopramide ($0.10) is inexpensive and may improve the effectiveness of the primary abortive medication.
Over-the-counter medications such as aspirin ($0.02/325 mg), Excadrin· ($0.09/tablet), ibuprofen ($0.04/200 mg), or naproxen sodium ($0.09/220 mg) are inexpensive and effective. "Triple therapy" combining metoclopramide, a nonsteroidal ant-inflammatory agent, and an ergotamine preparation may improve tolerance and effectiveness of the ergot. Locally compounded dihydroergotamine nasal spray is inexpensive ($0.78/1 mg spray). The cost of using oral sumatriptan can be almost halved by prescribing half of a 50-mg tablet.
Emergency department services are expensive. Huge cost savings occur through self-controlled administration of oral, rectal, or even intramuscular narcotic medications. Oral narcotic agents such as hydromorphone ($0.42/4 mg) and meperidine ($0.92/200 mg) are generally used in inadequate doses to be effective for severe migraine. Guidelines are given for more effective use of these agents.
Sophisticated comparative studies are needed to evaluate, not only the direct costs of medications, but all costs of treatment of an acute migraine attack, as well as Indirect costs to the patient, family, and society.     

Inpatient Treatment of Status Migraine With Dihydroergotamine in Children and Adolescents

Objective.— To assess the effectiveness of aggressive therapy of status migraine in children and adolescents.
Background.— Inpatient management of pediatric status migraine and intractable headache is limited because of a lack of studies and guidelines. Adult treatment is often based on anecdotal experience, although a few controlled studies have been reported. Added to that is the discomfort of general pediatricians and neurologists in using available effective treatments in pediatric patients (such as dihydroergotamine: DHE).
Methods.— Charts of all patients admitted to the neurology service, at Cincinnati Children's Hospital Medical Center—Department of Neurology, for inpatient treatment for intractable headache/status migraine over a 6-week period were reviewed. Demographics, evaluation, diagnosis, and treatment used were tabulated. Data on the effectiveness of the treatments provided were evaluated. Thirty-two total consecutive charts were retrospectively reviewed during that period.
Results.— Upon discharge, 74.4% of the patients were headache-free. The mean severity of the pain upon discharge was 1.02 ± 2.22 (using the 0-10 pain scale).
Conclusion.— From our review, DHE is very effective in treating and aborting an episode of status migraine and should be offered to children and adolescent patients who have failed their usual abortive therapy to prevent further severe disability that mainly affects their schooling and social activities.     

Dihydroergotamine Suppositories in a Headache Clinic

SYNOPSIS
Dihydroergotamine (DHE) is available in the United States for parenteral use. We report a preliminary trial of DHE suppositories in an outpatient headache clinic setting. Dihydroergotamine suppositories may be appropriate for patients with catamenial migraine and classic migraine in particular.     

Self-help Treatment for Migraine Headaches: A Controlled Outcome Study

SYNOPSIS
A self-help approach for the control of migraine headaches was evaluated. Self-help refers to a self-directed effort, without therapist contact aimed at reducing the symptoms of migraine. The experimental plan involved giving migraine headache patients one of two experimental books and then evaluating the effect.
Subjects were recruited through newspaper announcements and were required to have had at least two vascular headaches per month. During the first six weeks of the study, the baseline period, all subjects recorded headache frequency, intensity and duration. Subjects were then matched for headache frequency and then randomly assigned to receive either the treatment or control book.
The treatment book contained instructions for thermal biofeedback, relaxation and cognitive behavior therapy. A liquid crystal device for measuring fingertip temperature was also included. Instructions in the treatment book were written such that a self-help, no-therapist treatment could be followed by the subject. The control book was a popularly available paperback in which a series of case studies on headache treatment and diagnosis were discussed. It was selected because it was easy to read and contained information about headaches but did not necessarily direct the reader to start a self-help program.
Data was obtained for 51 subjects who completed a three- and six-month followup data collection period (treatment N = 22, control N = 29). There was a 62% decrease in headache frequency at six months for subjects who received the treatment book and a 14% drop for those who received the control book. Corresponding findings were also obtained for duration and pain levels of the headache as well as for prescribed medication use. Although the results indicated that this type of self-help treatment could be effective for many migraine patients, limitations and cautions in interpretation of these results were discussed.