Uncontrolled headache induced by oxcarbazepine

Headache induced by acute exposure to a specific drug constitutes an idiosyncratic side effect. Metabolic imbalance appears as the leading aetiology, among several other hypotheses. Either primary headaches show a higher susceptibility to this idiosyncratic reaction or a drug-induced primary headache evolves in intensity and duration, becoming uncontrolled until the complete discontinuation of the drug in consideration. The goal of this study is to describe three patients diagnosed with migraine and epilepsy (both under control) who evolved into status migrainosus after the introduction of oxcarbazepine (OXC), as part of a switch off from carbamazepine (CBZ). Twenty-four to seventy-two hours following the switch, all patients developed intractable headache, despite the use of different symptomatic drugs. Complete recovery of the headache symptoms occurred only after OXC was discontinued. We discuss the potential mechanisms associated to OXC and status migrainosus, drug-induced headaches and uncontrolled headaches.     

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.     

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.     

Management of Pediatric Migraine Headache in the Emergency Room and Infusion Center

Migraine is a common disorder that starts at an early age and takes a variable pattern from intermittent to chronic headache with several exacerbations throughout a lifetime. Children and adolescents are significantly affected. If an acute headache is not aborted by outpatient migraine therapy, it often causes severe disability, preventing the child from attending school and social events. Treating the acute severe headache aggressively helps prevent prolonged disability as well as possible chronification. Multiple medications are available, mostly for the outpatient management of an attack and include the use of over‐the‐counter anti‐inflammatory medications as well as prescribed medications in the triptan group. These therapies do sometime fail and the exacerbation can last from days to weeks. If the headache lasts 72 hours or longer it will fall in the category of status migrainosus. Status migrainosus is described as a severe disabling headache lasting 72 hours or more by the ICHD3 criteria. Disability is a major issue in children and adolescents and aggressive acute measures are to be taken to control it as soon as possible. Early aggressive intravenous therapy can be very effective in breaking the attack and allowing the child to be quickly back to normal functioning. This article reviews what is available for the treatment of pediatric primary headaches in the emergency room.     

Droperidol Treatment of Status Migrainosus and Refractory Migraine

We conducted a pilot study of intravenous droperidol in 35 patients (32 women and 3 men; mean age 43 years) with status migrainosus (n=25) or refractory migraine (n=10) in an ambulatory infusion center. Headache was graded as severe in 21 patients and moderate in 14. An intravenous line was started and kept open. Droperidol (2.5 mg) was given intravenously every 30 minutes until either three doses were given or the patient was completely or almost headache-free prior to the next dose.
Seven patients received one dose, 12 received two doses, and 16, three doses (mean 5.6 mg). Our success rate (headache-free or mild headache) was 88% (22 of 25) in patients with status migrainosus and 100% (10 of 10) in patients with refractory migraine. The average time to headache improvement was 40 minutes (n=35), to mild headache - 60 minutes (n=32), and to headache-free - 105 minutes (n=28). Nausea, vomiting, and light and sound sensitivity resolved in all but 5 patients. Four patients had an asymptomatic systolic blood pressure drop ≤ 20 mm Hg. Most patients were sedated (34 of 35). Five patients developed akathisia and I dystonia. At follow-up 24 hours after discharge, the recurrence rate (headache intensity from none or mild to moderate or severe) was 23% in status migrainosus and 10% in refractory migraine. Twenty-one patients were sedated, while 19 had extrapyramidal symptoms, mainly restlessness.
Droperidol is effective and safe in treating status migrainosus or refractory migraine. Hypotension was uncommon. Patients should be warned of sedation and akathisia.     

A fresh look at migraine therapy. New treatments promise improved management

Successful management of migraine headaches involves identifying and avoiding headache triggers and using appropriate abortive therapy once a headache is recognized. Pain relief measures include over-the-counter analgesics, parenteral NSAID therapy when needed, and use of antiemetics and cold packs. Narcotic analgesics are best used only as a "last resort" measure. Prophylactic therapy should be considered for patients who have more than two acute migraine attacks each month or whose daily activities are seriously compromised by headaches. For the patient in whom status migrainosus threatens well-being, hospitalization and more intensive therapy may be needed.     

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.     

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.     

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.     

Intravenous lignocaine (lidocaine) infusion for the treatment of chronic daily headache with substantial medication overuse

Patients with chronic daily headache with medication overuse are difficult to treat, especially when the doses of analgesia are substantial. We have previously shown that intravenous lignocaine (lidocaine) infusion is useful in maintaining pain control while the offending analgesic agent is withdrawn in these patients. The published data on long-term efficacy of this treatment is limited. We undertook a retrospective survey of 71 consecutive patients admitted for lignocaine infusion (mean 8.7 days) for treatment of chronic daily headache, with substantial analgesic abuse. Ninety percent of patients had a history of migraine headaches. In 80% of patients codeine was the predominant agent implicated in the analgesic rebound headaches (mean 1053 mg/week) and 24% used ergotamine-containing medications (mean 16 mg/week). Thirty-one percent frequently used injected narcotics. At completion 90% reported that their daily headache was absent or improved, and the analgesic agent was withdrawn successfully in 97%. At six month follow-up, 70% of patients reported that their daily headache was absent or improved and 72% of patients remained free of the offending analgesic agent. Intravenous lignocaine is a useful treatment in the management of chronic daily headache with substantial medication overuse. The benefits of the program last for at least six months.     

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.     

Diagnosis of migraine in children attending a pediatric headache clinic

The International Headache Society (IHS) criteria for migraine are not sufficient to diagnose migraine in children. Specifically, the duration and localization of the headache are different in children and adults with migraine. This study compared the formal IHS criteria with pediatric-amended IHS criteria and IHS criteria with the duration factor removed in children younger than 18 years. In addition, the older criteria by Vahlquist and by Prensky and Sommer were also compared. Finally, clinical diagnosis of migraine was compared with IHS criteria with the duration factor removed. The study showed that many children with a shorter duration headache have migraine and also that a number of children with a very long duration of headaches still fit the diagnosis of migraine. Unilateral headache is quite uncommon. The majority of children with migraine complained of bilateral headaches. It is concluded that the IHS criteria for pediatric migraine should be revised. We suggest making the duration factor a minor criteria for migraine in children or to exclude headaches lasting longer than 72 hours only in children younger than 15 years.     

Treatment of primary headache disorders with intravenous valproate: initial outpatient experience

OBJECTIVES: To evaluate the effectiveness of intravenous valproate in managing moderate to severe headaches. BACKGROUND: Despite major strides in the understanding of primary headache disorders, there have been few additions to acute headache management other than introduction of the triptans. An intravenous antiepileptic preparation, sodium valproate, has been reported to be effective in the management of status epilepticus and acute headache. METHODS: Between March 13, 2000 and October 11, 2000, we prospectively treated, in a nonrandomized and open-label study, every patient with a moderate to severe headache (4 or greater on a visual analog scale of head pain from 1 to 10) who wanted treatment with intravenous valproate. Using a verbal visual analog scale for pain (0 = no headache and 10 = most severe headache), we measured head pain before treatment and at time of discharge. The treating nurse monitored vital signs and side effects. A positive response was defined as a 50% or greater reduction at discharge in baseline pain. Information was collected regarding patient demographics, type of headache (according to criteria of the International Headache Society and that recently proposed for chronic headache), observation time in the treatment suite, cumulative dose of valproate, and use of concurrent medications. Univariable and multivariable correlates of response to treatment were identified using logistic regression analysis. RESULTS: One hundred thirty treatments were given to 89 women and 17 men, aged 17 to 76 years; 92 patients received only one treatment. Valproate doses ranged between 300 and 1200 mg. Thirty-three patients (31%) presented with episodic migraine, with or without aura; 45 patients (42%) presented with chronic daily headache with a history of episodic migraine, with or without aura (transformed migraine); 22 (21%) with unclassifiable chronic headache; 2 (2%) with episodic cluster headache; and 4 (4%) with chronic tension-type headache. For first treatments only, 61 patients (57.5%) responded to treatment, whereas for all treatments, 82 patients (63.1%) responded. Age and gender did not affect likelihood of response, whereas increasing duration of treatment (P=.003) and the additional use of analgesics (P=.021) were each negatively associated with response. Among headache types, unclassifiable chronic headache segregated from all other classified headaches in terms of poor response. Aside from rare dizziness (n = 2) and one spell interpreted as a pseudoseizure, no side effects were noted. CONCLUSIONS: Intravenous valproate is a safe, rapidly effective, abortive headache agent. It appears to be an effective analgesic for identifiable primary headaches, especially episodic headache, and less effective for unclassifiable chronic headache. Randomized, double-blind, controlled studies are warranted.     

Acute and interictal allodynia in patients with different headache forms: an Italian pilot study

OBJECTIVE: To investigate allodynia in patients with different primary headaches. BACKGROUND: Many migraineurs have allodynia during headache attacks; some may have allodynia outside attacks; allodynia may also be associated with other primary headaches. METHODS: A total of 260 consecutive primary headache patients presenting for the first time at a headache center, and 23 nonheadache controls answered written questions (subsequently repeated verbally) to determine the presence of acute and interictal allodynia. RESULTS: We divided the patients into: episodic migraine (N = 177), subdivided into only migraine without aura (N = 114) and those sometimes or always reporting migraine with aura (N = 63); episodic tension-type headache (N = 28); chronic headaches (headache > or = 15 days/month, N = 52), including chronic migraine, chronic tension-type headache, and medication-overuse headache; and other headache forms (N = 3). Acute allodynia was present in 132 (50.7%), significantly more often in patients sometimes or always suffering migraine with aura, and those with chronic headache forms, compared to patients with migraine without aura and episodic tension-type headache. Interictal allodynia was present in 63 (24.2%) patients, with significantly higher frequency in those having migraine with aura attacks than controls and common migraine patients. CONCLUSIONS: Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.     

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.     

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.     

Abortive Migraine Therapy in the Office with Dexamethasone and Prochlorperazine

SYNOPSIS
Corticosteroids are commonly used in the abortive therapy of status migrainosus. However, this practice is based more on clinical experience than on published data. At my office, over a period of two years, 108 patients (156 migraine episodes) were treated with intravenous dexamethasone. Most of these patients had prolonged migraines that had resisted other forms of abortive therapy. The first 22 patients (32 migraine episodes) were given 10 mg of dexamethasone over 5 minutes, the next 39 patients (55 migraine episodes) were given 20 mg over 10 minutes, and the last 47 patients (69 migraine episodes) were given 3.5 mg of prochlorperazine over 5 minutes followed by 20 mg of dexamethasone over 10 minutes. Adverse effects were minor and patients with episodic migraines responded more favorably than those with intractable migraines. In the episodic migraine groups, response rates ranged from 80–89%, relapse rates from 29–35%, and remission rates from 57–83%. After the intravenous injections, repetitive oral abortive therapy was often required to treat relapses and secure remission. Adding 3.5 mg of pro-chlorperazine to 20 mg of intravenous dexamethasone significantly shortened the response time.     

Management of Acute Intractable Headaches Using IV Therapy in an Office Setting

Twenty-seven consecutive patients with acute intractable headaches were treated in an office setting with an intravenous protocol of an antiemetic, hydrocortisone sodium succinate, and dihydroergotamine (DHE). All patients had significant pain relief within 45 minutes. Patients who were not pain-free post-treatment uniformly reported decreasing pain at the time of departure from the office. No patients required further treatment (including narcotic medication) for acute headache. All patients were followed for at least 24 hours. Adverse reactions were transient and mild. Akathisia was not uncommon and has probably been underestimated in previous studies.     

Daily sumatriptan for detoxification from rebound

Medications which provide symptomatic relief from headache can transform episodic migraine into chronic daily headache by propagating the daily headache, causing "rebound." It is possible to restore the episodic migraine pattern by using an inpatient course of intravenous dihydroergotamine. This study was undertaken to explore whether it was possible to use oral sumatriptan in the outpatient setting as a bridge to detoxification for patients with chronic daily headache due to medication overuse. All patients had previously met International Headache Society (IHS) criteria for episodic migraine and currently had greater than 15 days of headache per month for greater than 1 month. These patients were advised to take 25 mg sumatriptan by mouth three times a day for 10 days or until they were headache-free for 24 hours. Results reveal that of the 26 patients who started the protocol, 58% had reverted to an episodic migraine pattern at 1 month, and 69% were no longer having chronic daily headache at 6 months. This study demonstrates that it is possible to detoxify patients with rebound headaches using oral sumatriptan during the withdrawal period in an outpatient setting.