Pediatric Inpatient Headache Therapy: What is Available

Status migrainosus is defined by the international classification of headache disorders (ICHD) criteria as a debilitating migraine lasting more then 72 hours. The epidemiology of status migrainosus is still unknown in adult and children, and frequently underdiagnosed. Children and adolescents often end up in the emergency room with an intractable headache that failed outpatient therapy. Six to seven percent of these children do not respond to acute infusion therapy and require hospitalization. It is imperative that more aggressive therapy is considered when patients are affected by a severe intractable headache to prevent further disability and returning the child to baseline activity. Multiple therapies are available for adults and children. Studies for acute therapy in the emergency room are available in adults and pediatric groups. Small studies are available for inpatient therapy in children and, along with available therapies for children and adolescents, are described in this review. A review of the literature shows growing evidence regarding the use of dihydroergotamine intravenously once patients are hospitalized. Effectiveness and safety have been proven in the last decades in adults and small studies in the pediatric populations.     

The Hospital Management of Severe Migrainous Headache

In a two year period, 47 patients with migraine were hospitalized for the management of severe headache; 18 had acute migraine (duration less than 72 hours), 17 had status migrainosus (duration by definition more than 72 hours), and 12 had chronic daily headaches qualitatively of a migraine type. Treatment in all comprised cessation of all previous medication, plus one of the following: intravenous DHE, intravenous lidocaine, a combination of lidocaine + DHE, or subcutaneous sumatriptan. Improvement from DHE, lidocaine, or both was slow and often incomplete. Sumatriptan was not used in patients with chronic daily headaches; in the 8 cases of acute migraine or status migrainosus in which it was used, improvement was rapid and complete in seven.     

Prevalence and burden of chronic migraine in adolescents: results of the chronic daily headache in adolescents study (C-dAS)

(Headache 2011;51:693‐706) Objective.— To estimate the prevalence of chronic migraine (CM) among adolescents and to describe the epidemiologic profile, headache characteristics, disability, and healthcare utilization of adolescents with CM in the USA. Background.— Chronic daily headache (CDH) and CM occur in children and adolescents, but are poorly understood in these populations because their presentation is different from that in adults. It may be difficult to assign a definitive diagnosis to young people suffering from CDH because symptoms may fail to meet the criteria for one of the CDH subtypes. Methods.— A large sample of households with at least one resident aged 12 to 19 years was selected in balance with the US Census. Data were collected in 3 phases: (1) mailed questionnaire; (2) telephone interview; and (3) 30‐day interactive voice response system diary. CM prevalence was estimated by adapting the second edition of the International Classification of Headache Disorders criteria for CM to include pediatric migraine diagnostic criteria. The population was stratified for medication overuse. Medication overuse was defined as 15 or more days per month of acute medication use. Included in the study were measures of headache characteristics, headache impact (Headache Impact Test), disability (Pediatric Migraine Disability Assessment), and healthcare and medication use. Data are reported on subjects 12 to 17 years of age only. Results.— The US adolescent (12‐17 years) prevalence rate for CM was 0.79% (0.00‐1.70) excluding those with medication overuse and 1.75% (0.62‐2.89) when adolescents with medication overuse were included. The majority of adolescents with CM had Headache Impact Test scores greater than or equal to 60, indicating severe headache impact, and mean Pediatric Migraine Disability Assessment scores greater than 17, indicating severe headache and disability. The majority of adolescents with CM (approximately 60%) had not visited a healthcare provider in the previous year and less than one in 5 reported taking medications to prevent headaches during the last month. Conclusions.— Results suggest that CM occurs less frequently in adolescents than adults, but like adults, adolescents are severely burdened by the disorder. Data support an unmet medical need; however, the development of optimal criteria for diagnosing adolescents with CM is critical to fully understanding how medical needs can be met within this complex population.     

HIT‐6 and MIDAS as Measures of Headache Disability in a Headache Referral Population

(Headache 2010;50:383‐395) Objective.— The objective of this study was to compare the headache impact test (HIT‐6) and the migraine disability assessment scale (MIDAS) as clinical measures of headache‐related disability. Background.— The degree of headache‐related disability is an important factor in treatment planning. Many quality of life and headache disability measures exist but it is unclear which of the available disability measures is the most helpful in planning and measuring headache management. Methods.— We compared HIT‐6 and MIDAS scores from 798 patients from the Canadian Headache Outpatient Registry and Database (CHORD). Correlation and regression analyses were used to examine the relationships between the HIT‐6 and MIDAS total scores, headache frequency and intensity, and Beck Depression Inventory (BDI‐II) scores. Results.— A positive correlation was found between HIT‐6 and MIDAS scores (r = 0.52). The BDI‐II scores correlated equally with the HIT‐6 and the MIDAS (r = 0.42). There was a non‐monotonic relationship between headache frequency and the MIDAS, and a non‐linear monotonic relationship between headache frequency and the HIT‐6 (r = 0.24). The correlation was higher between the intensity and the HIT‐6 scores (r = 0.46), than MIDAS (r = 0.26) scores. Seventy‐nine percent of patients fell into the most severe HIT‐6 disability category, compared with the 57% of patients that fell into the most severe MIDAS disability category. Significantly more patients were placed in a more severe category with the HIT‐6 than with the MIDAS (McNemar chi‐square = 191 on 6 d.f., P < .0001). Conclusions.— The HIT‐6 and MIDAS appear to measure headache‐related disability in a similar fashion. However, some important differences may exist. Headache intensity appears to influence HIT‐6 score more than the MIDAS, whereas the MIDAS was influenced more by headache frequency. Using the HIT‐6 and MIDAS together may give a more accurate assessment of a patient's headache‐related disability.     

Behaviour during attacks and assessment of intensity in primary headaches of children and adolescents

Assessment of attack intensity in primary headaches of paediatric age has not received great attention in the literature to date and in the international classification the criteria to define pain intensity are also not specified. The purpose of this research was to evaluate whether behaviour during attacks, reported by the child or a parent, can be used as a measure of attack disability, and so as an indirect measure of attack intensity in primary headaches of children and adolescents. The subjects were 320 patients aged between 3 and 14 years (mean age 9.9 years, SD 2.6 years) affected by primary recurrent headaches and first seen at a headache clinic. Twelve variables taken from their history were considered and sequentially analysed with multiple correspondence analysis and cluster analysis. Five types of behaviour during attacks were identified: (i) the child (or the parent) is unable to answer the questions or the child has no limitation in activities; (ii) the child may have some activity limitation, but only in lively games; (iii) the child has limitations in daily life with regard also to quiet activities; (iv) at least during some attacks the child lies down with closed eyes or in the dark; (v) during each attack the child lies down with closed eyes or in the dark. The least important variables for the identification of the five behaviour types were studying at school and absence from school. There are some limitations in considering child's behaviour as a measure of attack intensity/disability; one of these is the fact that it was found to be related to the educational level of the mother. However, behaviour during attacks, reported by the child or the parent, provides useful information independently of child's age and, together with the score of pain, when this is given, it can be used as measure of attack intensity.     

Does the Addition of Dexamethasone to Standard Therapy for Acute Migraine Headache Decrease the Incidence of Recurrent Headache for Patients Treated in the Emergency Department? A Meta‐analysis and Systematic Review of the Literature

Objectives: Neurogenic inflammation is thought to play a role in the development and perpetuation of migraine headache. The emergency department (ED) administration of dexamethasone in addition to standard antimigraine therapy has been used to decrease the incidence of recurrent headaches at 24 to 72 hours following evaluation. This systematic review details the completed trials that have evaluated the use of dexamethasone in this role. Methods: The authors searched MEDLINE, EMBASE, CINAHL, LILACS, recent emergency medicine scientific abstracts, and several prepublication trial registries for potential investigations related to the research question. The authors included studies that incorporated randomized, double‐blind, placebo‐controlled methodology and that were performed in the ED. A fixed‐effects and random‐effects model was used to obtain summary risk ratios (RRs) and 95% confidence intervals (CIs) for the self‐reported outcome of moderate or severe headache on follow‐up evaluation. Results: A pooled analysis of seven trials involving 742 patients suggests a modest but significant benefit when dexamethasone is added to standard antimigraine therapy to reduce the rate of patients with moderate or severe headache on 24‐ to 72‐hour follow‐up evaluation (RR = 0.87, 95% CI = 0.80 to 0.95; absolute risk reduction = 9.7%). The treatment of 1,000 patients with acute migraine headache using dexamethasone in addition to standard antimigraine therapy would be expected to prevent 97 patients from experiencing the outcome of moderate or severe headache at 24 to 72 hours after ED evaluation. The sensitivity analysis yielded similar results with sequential trial elimination, indicating that no single trial was responsible for the overall result. Adverse effects related to the administration of a single dose of dexamethasone were infrequent, mild, and transient. Conclusions: These results suggest that dexamethasone is efficacious in preventing headache recurrence and safe when added to standard treatment for the management of acute migraine headache in the ED.     

Chronic daily headache in children and adolescents

OBJECTIVE: To describe the clinical features of children with chronic daily headache (CDH) and examine the usefulness of the International Classification of Headache Disorders-II. BACKGROUND: Few data are available on chronic daily headache and analgesic overuse in children and adolescents and there are no specific criteria for headache in children. METHODS: We retrospectively reviewed all charts of 79 children and adolescents (<16 years) with headache on > or =15 days/month presenting to the outpatient clinic of the Department of Neurology of the Leiden University Medical Center between 1994 and 2001. We classified their headaches according to the International Classification of Headache Disorders-II. RESULTS: Fifty-seven (72%) children had chronic daily headache for more than 6 months, with a duration of more than 4 hours a day in 60% of them. Quality, severity, and location of pain varied. Sixty patients (76%) used analgesics, 10 patients more than one type. Thirteen patients (16%) used analgesics daily. In one-third of patients, headache led to frequent school absenteeism and sleeping problems. Twenty-eight (35%) patients could be classified, 17 patients (22%) as chronic tension-type headache, 5 patients (6%) as chronic migraine, and 6 patients (8%) as probable medication overuse headache. Fifteen patients (19%) did not fit into any category and 36 (46%) could not be classified due to insufficient data. CONCLUSIONS: Chronic daily headache in children is a serious disorder. A relatively large number of patients overuse medication and it leads to frequent school absenteeism and sleeping problems. It remains difficult to classify their headaches with the new criteria for headache disorders.     

Headache Disability Among Adolescents: A Student Population‐Based Study

(Headache 2010;50:210‐218) Objective.— To examine the extent and to identify the relevant predictors of headache disabilities in adolescents. Background.— Headaches are common in adolescents but their impact and related factors have not been extensively studied in adolescent communities. Method.— We recruited and surveyed 3963 students aged 13‐15 from 3 middle schools using self‐administered questionnaires. The questionnaires were used to make 3 assessments: (1) headaches were diagnosed using a validated headache questionnaire; (2) headache disabilities were valuated using the 6‐question Pediatric Migraine Disability Assessment; (3) depression was measured using the Adolescent Depression Inventory. Results.— The student response rate was 93%. In total, 484 students (12.2%) had migraines with or without auras, 444 (11.2%) had probable migraines, and 1092 (27.6%) had tension‐type headaches. The students with migraine had the highest Pediatric Migraine Disability Assessment scores (10.7 ± 20.0); whereas, the students with tension‐type headaches had the lowest scores (2.0 ± 4.4). Logistic regression analyses indicated that there were a number of independent predictors for moderate to severe headache‐related disability (Pediatric Migraine Disability Assessment score ≥31), including a migraine or probable migraine diagnosis, a higher depression score, severe headache intensity, and frequent headaches. Conclusions.— The Pediatric Migraine Disability Assessment provides a simple tool to measure the impact of headaches in adolescents. Adolescents with migraine headaches suffered the greatest level of disability. Higher depression scores were associated with more severe headache‐related disabilities in adolescents, independent of headache frequency and severity.     

Acute Migraine Treatment in Adults

There are many options for acute migraine attack treatment, but none is ideal for all patients. This study aims to review current medical office‐based acute migraine therapy in adults and provides readers with an organized approach to this important facet of migraine treatment. A general literature review includes a review of several recent published guidelines. Acetaminophen, 4 nonsteroidal anti‐inflammatory drugs (NSAIDs) (ibuprofen, acetylsalicylic acid [ASA], naproxen sodium, and diclofenac potassium), and 7 triptans (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan) have good evidence for efficacy and form the core of acute migraine treatment. NSAID–triptan combinations, dihydroergotamine, non‐opioid combination analgesics (acetaminophen, ASA, and caffeine), and several anti‐emetics (metoclopramide, domperidone, and prochlorperazine) are additional evidence‐based options. Opioid containing combination analgesics may be helpful in specific patients, but should not be used routinely. Clinical features to be considered when choosing an acute migraine medication include usual headache intensity, usual rapidity of pain intensity increase, nausea, vomiting, degree of disability, patient response to previously used medications, history of headache recurrence with previous attacks, and the presence of contraindications to specific acute medications. Available acute medications can be organized into 4 treatment strategies, including a strategy for attacks of mild to moderate severity (strategy one: acetaminophen and/or NSAIDs), a triptan strategy for patients with severe attacks and for attacks not responding to strategy one, a refractory attack strategy, and a strategy for patients with contraindications to vasoconstricting drugs. Acute treatment of migraine attacks during pregnancy, lactation, and for patients with chronic migraine is also discussed. In chronic migraine, it is particularly important that medication overuse is eliminated or avoided. Migraine treatment is complex, and treatment must be individualized and tailored to the patient's clinical features. Clinicians should make full use of available medications and formulations in an organized approach.     

Low migraine headache recurrence with naratriptan: clinical parameters related to recurrence

OBJECTIVE: To evaluate clinical parameters that may affect the incidence of headache recurrence or the time to headache recurrence, or both, in migraineurs treated with naratriptan, 2.5-mg tablets. BACKGROUND: The incidence of headache recurrence within 24 hours of treatment with naratriptan, 2.5-mg tablets (17%-28%), is lower than that reported for other currently available selective serotonin agonists. Identifying clinical parameters that influence headache recurrence may further reduce the incidence of headache recurrence or prolong the time to recurrence, or both, for naratriptan-treated patients. METHODS: We examined the effects of three clinical parameters (predose pain severity, headache duration prior to treatment, and relief status 4 hours post dose) on the incidence of and time to headache recurrence across four placebo-controlled naratriptan clinical trials. The impact of these parameters on headache recurrence was examined individually and in combination. RESULTS: Predose pain severity had no effect on the incidence of headache recurrence (overall 23%; moderate 22%, severe 23%). The median time to recurrence was longer for patients with moderate pain before treatment compared with patients with severe pain before treatment (14.5 hours versus 9.3 hours, respectively). Overall time to headache recurrence was 11.8 hours. Patients with headache recurrence reported a longer time until they treated the headache compared with patients without headache recurrence (median, 145 minutes versus 97.5 minutes). Patients who treated headache pain within 3 hours of onset had a lower incidence of headache recurrence (20%) than patients who treated their headache more than 3 hours after onset (28%). Patients with no pain 4 hours post dose had a lower incidence of and a longer time to headache recurrence compared with patients with mild pain 4 hours post dose (17% versus 32%; median, 17.8 hours versus 8.1 hours, respectively). The interaction of all three clinical parameters was significant in predicting headache recurrence. CONCLUSIONS: The overall incidence of headache recurrence is low after naratriptan, 2.5 mg, compared with other currently available selective serotonin agonists. Predose pain severity, time to treatment, and 4-hour relief status appear related to the incidence of or time to headache recurrence, or both. Treating less severe migraine attacks, treating earlier within an attack, and obtaining complete relief post dose may enhance the low incidence of headache recurrence and achieve longer times to recurrence with naratriptan, 2.5 mg.     

Management of Chronic Daily Headache: Challenges in Clinical Practice

Chronic daily headache (CHD) refers to a category of headache disorders that are characterized by headaches occurring on more than 15 days per month. This category is subdivided into long- and short-duration (>4 or <4 hours) CDH disorders based on the duration of individual headache attacks. Examples of long-duration CDH include transformed migraine (TM), chronic migraine (CM), new daily persistent headache (NDPH), acute medication overuse headache, and hemicrania continua (HC). The goal of this review is to enable clinicians to accurately diagnose and effectively manage patients with long-duration CDH. Patients with CDH often require an aggressive and comprehensive treatment approach that includes a combination of acute and preventive medications, as well as nondrug therapies.     

Managing chronic headaches in the clinic

Chronic daily headache (CDH), which is often linked to a history of migraine, tension-type headache and the abuse of headache medications, and cluster headache are the best known of the chronic headaches. These headaches may not be well recognised or well treated in primary care. This article outlines the development of management algorithms for these headache subtypes, designed for use by the primary care physician with an interest in headache. Principles of care for chronic headaches include implementation of screening procedures, differential diagnosis, tailoring of management to the individual's needs, proactive follow-up and a team approach to care. These principles can be customised to the headache subtype by the selection of appropriate therapies. The optimal treatments for CDH include physical therapy to the neck if there is any stiffness there, withdrawal of abused medications and treatment of any subsequent withdrawal symptoms and headache prophylaxis, together with the provision of acute medications as rescue therapy. Optimal treatments for cluster headache include short- and long-term prophylaxis to prevent the headaches developing and acute medications for use as rescue. If treatment is ineffective, alternative medications can be provided at follow-up, with the possibility of referral for refractory patients.     

Zolmitriptan Nasal Spray in the Acute Treatment of Cluster Headache: A Meta-Analysis of Two Studies

Objective.— To conduct an individual subject meta‐analysis of available controlled studies of zolmitriptan nasal spray in the acute treatment of cluster headache. Background.— Two double‐blind, placebo‐controlled, randomized, crossover studies of zolmitriptan nasal spray in the acute treatment of cluster headache, with similar patient populations, protocol designs, doses, and clinical endpoints have been published. Methods.— In both double‐blind studies, each patient was to treat 3 attacks, 1 with placebo, 1 with zolmitriptan 5 mg, and 1 with zolmitriptan 10 mg in a randomized, crossover manner. Headache intensity was rated on a 5‐point scale (none to very severe). The primary endpoint was headache relief at 30 minutes post dose: reduction from moderate, severe, or very severe pain to mild or none. A multilevel, random‐effects, logistic regression model was used to analyze the data. Results.— A total of 121 patients (100 male; 64.5% with episodic cluster headache) provided efficacy data for at least 1 attack. Zolmitriptan 5 mg and 10 mg were significantly more effective at providing headache relief at 30 minutes post treatment than placebo (odds ratio 3.48; 95% confidence interval 1.49‐8.10 and odds ratio 8.68; 95% confidence interval: 3.35‐22.5, respectively). For episodic cluster headache, response rates were 35.6%, 51.7%, and 73.7% for placebo, zolmitriptan 5 mg (odds ratio 2.5; P = .06 vs placebo), and 10 mg (odds ratio 9.9; P < .001 vs placebo), respectively. For chronic cluster headache, response rates were 17.2%, 41.9%, and 40.7% for placebo, zolmitriptan 5 mg (odds ratio 8.1; P = .035), and 10 mg (odds ratio 7.6; P = .046), respectively. Zolmitriptan was well tolerated in both studies with no serious adverse events reported. Conclusion.— Zolmitriptan nasal spray at a dose of 5 mg and 10 mg is efficacious in the acute treatment of episodic and chronic cluster headache.     

Age-dependent relationships among pain, depressive symptoms, and functional disability in youth with recurrent headaches

OBJECTIVE: To assess age differences associated with depressive symptoms and functional disability in children and adolescents with recurrent headache. BACKGROUND: Research has indicated that psychological factors, especially depression, are related to the extent and nature of functional disability experienced from headaches. There is a lack of research examining how age impacts the relationship between pain, psychological factors, and activity restriction in children and adolescents with recurrent headache. METHODS: Seventy-seven participants from a pediatric neurology clinic completed self-report measures of pain intensity, depressive symptoms, and functional disability. RESULTS: Findings demonstrated a significant positive correlation between pain and functional disability, and depressive symptoms and functional disability for children. Correlations for adolescents failed to reach significance. Functional disability emerged as a mediator between headache pain and depressive symptoms for children but not for adolescents. CONCLUSIONS: Results indicate potentially important age differences when examining the impact of functional disability on depressive symptoms in this sample. Findings suggest that functional disability may contribute to depressive symptoms differently for children versus adolescents with recurrent headache. Age-specific interventions that differentially focus on the specific roles that pain, depressive symptoms, and disability have for children and adolescents with recurrent headache may be warranted.     

Factors associated with triptan use in episodic migraine: results from the American Migraine Prevalence and Prevention Study

Background.— Though triptans are considered the standard of acute therapy for migraine attacks with headache‐related disability, they are used by the minority of potentially eligible persons. Understanding the socio‐demographic and headache features that predict triptan use may help to clarify barriers to optimal treatment. Objective.— To assess the sociodemographic and headache features associated with triptan use in a US population sample of persons with episodic migraine. Methods.— The American Migraine Prevalence and Prevention Study (AMPP) is a longitudinal study conducted in a representative sample of US headache sufferers. Episodic migraineurs (n = 11,388) who provided treatment data in 2005 were included in the current analyses. We assessed factors associated with triptan use through univariate and multivariate analyses. Multivariate analyses were adjusted for sociodemographic factors, headache‐related disability, cutaneous allodynia, depression, and preventive headache medication use. Results.— Among persons with episodic migraine, 18.31% reported current use of triptans for acute headache treatment. In univariate analyses, triptan use was most common in midlife (ages 30‐59), among females, and was more common in Caucasians than in African Americans. Triptan use increased with headache frequency, headache‐related disability and allodynia, but decreased among persons with depression. In multivariate analyses, female gender, Caucasian race, age 40‐49, higher levels of education (college or higher), annual household income of ≥$40,000, having health insurance, the presence of cutaneous allodynia, greater headache‐related disability, and preventive medication use for migraine were significantly associated with triptan use. Conclusions.— Less than 1 in 5 persons with migraine in the United States who were respondents to this survey used triptans for acute headache treatment over the course of a year. Several markers of severe headache, including disability and allodynia, were associated with increased triptan use. Groups less likely to get triptans included males, African Americans, older adults, and the uninsured. Predictors of use provide insight into groups with unmet treatment needs.     

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.