Chronic daily headache in U.S. soldiers after concussion

(Headache 2012;52:732‐738) Objective.— To determine the prevalence and characteristics of, and factors associated with, chronic daily headache (CDH) in U.S. soldiers after a deployment‐related concussion. Methods.— A cross‐sectional, questionnaire‐based study was conducted with a cohort of 978 U.S. soldiers who screened positive for a deployment‐related concussion upon returning from Iraq or Afghanistan. All soldiers underwent a clinical evaluation at the Madigan Traumatic Brain Injury Program that included a history, physical examination, 13‐item self‐administered headache questionnaire, and a battery of cognitive and psychological assessments. Soldiers with CDH, defined as headaches occurring on 15 or more days per month for the previous 3 months, were compared to soldiers with episodic headaches occurring less than 15 days per month. Results.— One hundred ninety‐six of 978 soldiers (20%) with a history of deployment‐related concussion met criteria for CDH and 761 (78%) had episodic headache. Soldiers with CDH had a median of 27 headache days per month, and 46/196 (23%) reported headaches occurring every day. One hundred seven out of 196 (55%) soldiers with CDH had onset of headaches within 1 week of head trauma and thereby met the time criterion for posttraumatic headache (PTHA) compared to 253/761 (33%) soldiers with episodic headache. Ninety‐seven out of 196 (49%) soldiers with CDH used abortive medications to treat headache on 15 or more days per month for the previous 3 months. One hundred thirty out of 196 (66%) soldiers with CDH had headaches meeting criteria for migraine compared to 49% of soldiers with episodic headache. The number of concussions, blast exposures, and concussions with loss of consciousness was not significantly different between soldiers with and without CDH. Cognitive performance was also similar for soldiers with and without CDH. Soldiers with CDH had significantly higher average scores on the posttraumatic stress disorder (PTSD) checklist compared to soldiers with episodic headaches. Forty‐one percent of soldiers with CDH screened positive for PTSD compared to only 18% of soldiers with episodic headache. Conclusions.— The prevalence of CDH in returning U.S. soldiers after a deployment‐related concussion is 20%, or 4‐ to 5‐fold higher than that seen in the general U.S. population. CDH following a concussion usually resembles chronic migraine and is associated with onset of headaches within the first week after concussion. The mechanism and number of concussions are not specifically associated with CDH as compared to episodic headache. In contrast, PTSD symptoms are strongly associated with CDH, suggesting that traumatic stress may be an important mediator of headache chronification. These findings justify future studies examining strategies to prevent and treat CDH in military service members following a concussive injury.     

Botulinum toxin type a for the prophylaxis of chronic daily headache: subgroup analysis of patients not receiving other prophylactic medications: a randomized double-blind, placebo-controlled study

OBJECTIVE: To assess the efficacy and safety of botulinum toxin type A (BoNT-A; BOTOX, Allergan, Inc., Irvine, CA) for the prophylaxis of headaches in patients with chronic daily headache (CDH) without the confounding factor of concurrent prophylactic medications. BACKGROUND: Several open-label studies and an 11-month, randomized, double-blind, placebo-controlled study suggest that BoNT-A may be an effective therapy for the prophylaxis of headaches in patients with CDH. DESIGN AND METHODS: This was a subgroup analysis of an 11-month, randomized double-blind, placebo-controlled study of BoNT-A for the treatment of adult patients with 16 or more headache days per 30-day periods conducted at 13 North American study centers. All patients had a history of migraine or probable migraine. This analysis involved data for patients who were not receiving concomitant prophylactic headache medication and who constituted 64% of the full study population. Following a 30-day screening period and a 30-day single-blind, placebo injection, eligible patients were injected with BoNT-A or placebo and assessed every 30 days for 9 months The following efficacy measures were analyzed per 30-day periods: change from baseline in number of headache-free days; change from baseline in headache frequency; proportion of patients with at least 30% or at least 50% decrease from baseline in headache frequency; and change from baseline in mean headache severity. Acute medication use was assessed, and adverse events were recorded at each study visit. RESULTS: Of the 355 patients randomized in the study, 228 (64%) were not taking prophylactic medication and were included in this analysis (117 received BoNT-A, 111 received placebo injections). Mean age was 42.4+/-10.90 years; the mean frequency of headaches per 30 days at baseline was 14.1 for the BoNT-A group and 12.9 for the placebo group (P=.205). After two injection sessions, the maximum change in the mean frequency of headaches per 30 days was -7.8 in the BoNT-A group compared with only -4.5 in the placebo group (P=.032), a statistically significant between-group difference of 3.3 headaches. The between-group difference favoring BoNT-A treatment continued to improve to 4.2 headaches after a third injection session (P=.023). In addition, BoNT-A treatment at least halved the frequency of baseline headaches in over 50% of patients after three injection sessions compared to baseline. Statistically significant differences between BoNT-A and placebo were evident for the change from baseline in headache frequency and headache severity for most time points from day 180 through day 270. Only 5 patients (4 patients receiving BoNT-A treatment; 1 patient receiving placebo) discontinued the study due to adverse events and most treatment-related events were transient and mild to moderate in severity. CONCLUSIONS: BoNT-A is an effective and well-tolerated prophylactic treatment in migraine patients with CDH who are not using other prophylactic medications.     

A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine

(Headache 2011;51:21‐32) Objective.— This multi‐center pilot study compared the efficacy of onabotulinumtoxinA with topiramate (a Food and Drug Administration approved and widely accepted treatment for prevention of migraine) in individuals with chronic migraine (CM). Methods.— A total of 59 subjects with CM were randomly assigned to one of 2 groups: Group 1 (n = 30) received topiramate plus placebo injections, Group 2 (n = 29) received onabotulinumtoxinA injections plus placebo tablets. Subjects maintained daily headache diaries over a 4‐week baseline period and a 12‐week active study period. The primary endpoint was the Physician Global Assessment, which measured the treatment responder rate and indicated improvement in both groups over 12 weeks. Secondary endpoints, measured at weeks 4 and 12, included headache days per month, migraine days, headache‐free days, days on acute medication, severity of headache episodes, Migraine Impact & Disability Assessment, Headache Impact Test, effectiveness of and satisfaction with current treatment on the amount of medication needed, and the frequency and severity of migraine symptoms. At 12 weeks subjects were re‐evaluated and tapered off oral study medications over a 2‐week time period. Subjects not reporting a >50% reduction of headache frequency at 12 weeks were invited to participate in a 12‐week open label extension study with onabotulinumtoxinA. Of these, 20 subjects, 9 from the Topiramate Group and 11 from the OnabotulinumtoxinA Group, volunteered for this extension from weeks 14 to 26. Results.— This study demonstrated positive benefit for both onabotulinumtoxinA and topiramate in subjects with CM. Overall, the results were statistically significant within groups but not between groups. By week 26, subjects had a reduction of headache days per month compared with baseline. This was a significant within‐group finding. Conclusion.— OnabotulinumtoxinA and topiramate demonstrated similar efficacy for subjects with CM as determined by Global Physician Assessment and supported by multiple secondary endpoint measures.     

Headache and Symptoms of Temporomandibular Disorder: An Epidemiological Study

(Headache 2010;50:231‐241) Objectives.— A population‐based cross‐sectional study was conducted to estimate the prevalence of migraine, episodic tension‐type headaches (ETTH), and chronic daily headaches (CDH), as well as the presence of symptoms of temporomandibular disorders (TMD) in the adult population. Background.— The potential comorbidity of headache syndromes and TMD has been established mostly based on clinic‐based studies. Methods.— A representative sample of 1230 inhabitants (51.5% women) was interviewed by a validated phone survey. TMD symptoms were assessed through 5 questions, as recommended by the American Academy of Orofacial Pain, in an attempt to classify possible TMD. Primary headaches were diagnosed based on the International Classification of Headache Disorders. Results.— When at least 1 TMD symptom was reported, any headache happened in 56.5% vs 31.9% (P < .0001) in those with no symptoms. For 2 symptoms, figures were 65.1% vs 36.3% (P < .0001); for 3 or more symptoms, the difference was even more pronounced: 72.8% vs 37.9%. (P < .0001). Taking individuals without headache as the reference, the prevalence of at least 1 TMD symptom was increased in ETTH (prevalence ratio = 1.48, 95% confidence interval = 1.20‐1.79), migraine (2.10, 1.80‐2.47) and CDH (2.41, 1.84‐3.17). At least 2 TMD symptoms also happened more frequently in migraine (4.4, 3.0‐6.3), CDH (3.4; 1.5‐7.6), and ETTH (2.1; 1.3‐3.2), relative to individuals with no headaches. Finally, 3 or more TMD symptoms were also more common in migraine (6.2; 3.8‐10.2) than in no headaches. Differences were significant for ETTH (2.7 1.5‐4.8), and were numerically but not significant for CDH (2.3; 0.66‐8.04). Conclusion.— Temporomandibular disorder symptoms are more common in migraine, ETTH, and CDH relative to individuals without headache. Magnitude of association is higher for migraine. Future studies should clarify the nature of the relationship.     

Effectiveness of amitriptyline in the prophylactic management of childhood headaches

OBJECTIVE: To study the effectiveness of a standardized dose of amitriptyline, 1 mg/kg, for childhood headaches. BACKGROUND: Amitriptyline has been shown to be effective for the prophylaxis of migraine in adults. Studies in children, however, have been quite limited. In adults, the suggested effective dose range is 10 to 150 mg. In children, a standardized dosage is often not used, resulting in a dosage range in clinical practice that often varies from a very low dose to a dose equivalent to that used in adults. METHODS: Children with more than three headaches per month were treated with amitriptyline, slowly increasing the dose to 1 mg/kg per day. The frequency, severity, and duration of their headaches were initially evaluated and subsequently measured at each follow-up evaluation. Two hundred seventy-nine children had headaches occurring frequently enough to indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with amitriptyline. The average age at presentation was 12.0 (+/- 3.0) years. The ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1 (+/- 10.1) days per month. The average severity was 6.84 (+/- 1.67) on a 10-point pain scale. The average duration was 11.5 (+/- 15.0) hours. The most frequent diagnoses using International Headache Society criteria were migraine (60.6%), migraine with aura (7.9%), and tension-type headache (10.4%). Of these children, 146 have been seen for at least one follow-up examination, occurring on average 67.3 (+/- 32.3) days after beginning prophylactic treatment. RESULTS: A total of 84.2% of the children reported an overall perception of being better, while 11.6% reported being the same. The frequency of headaches improved to 9.2 (+/- 10.0) days per month. The average severity was reduced to 5.1 (+/- 2.1), and the average duration was reduced to 6.3 (+/- 11.1) hours. If daily or continuous headaches were excluded, the improvements were more marked. Minimal side effects were reported from these children and their families. Long-term evaluation (156 to 415 days) showed continued sustained improvement. CONCLUSIONS: Amitriptyline is an effective prophylactic medication for children with frequent headaches. A standardized dosing regimen results in a significant number of children responding with minimal side effects. The children are able to tolerate this dosing scheme and demonstrate good adherence to a dosing schedule of once a day.     

Chronic Headache and Comorbibities: A Two‐Phase,Population‐Based,Cross‐Sectional Study

Background.— Studies using resources of a public family health program to estimate the prevalence of chronic daily headaches (CDH) are lacking. Objectives.— To estimate the 1‐year prevalence of CDH, as well as the presence of associated psychiatric and temporomandibular disorders (TMD) comorbidities, on the entire population of a city representative of the rural area of Brazil. Methods.— This was a cross‐sectional, population‐based, 2‐phase study. In the first phase, health agents interviewed all individuals older than 10 years, in a rural area of Brazil. In the second stage, all individuals who reported headaches on 4 or more days per week were then evaluated by a multidisciplinary team. CDH were classified according to the second edition of the International Classification of Headache Disorders (ICHD‐2). Medication overuse headache was diagnosed, as per the ICHD‐2, after detoxification trials. Psychiatric comorbidities and TMD were diagnosed based on the DSM‐IV and on the Research Diagnostic Criteria for Temporomandibular Disorders criteria, respectively. Results.— A total of 1631 subjects participated in the direct interviews. Of them, 57 (3.6%) had CDH. Chronic migraine was the most common of the CDH (21, 36.8%). Chronic tension‐type headache (10, 17.5%), medication overuse headache (13, 22.8%) and probable medication overuse headache (10, 17.5%) were also common. Psychiatric disorders were observed in 38 (67.3%) of the CDH subjects. TMD were seen in 33 (58.1)% of them. Conclusions.— The prevalence of CDH in the rural area of Brazil is similar to what has been reported in previous studies. A significant proportion of them have psychiatric comorbidities and/or TMD. In this sample, comorbidities were as frequent as reported in convenience samples from tertiary headache centers. (Headache 2010;50:1306‐1312)     

Classical homeopathic treatment of chronic headaches

We conducted a randomized, placebo-cor rolled, double-blind clinical trial in order to determine the efficacy of classical homeopathic therapy in patients with chronic headaches. After 6 weeks of baseline observation, patients received either the prescribed individualized homeopathic medication or an indistinguishable placebo for 12 weeks. Outcome parameters were headache frequency, duration, and intensity, measured daily by diary. Use of medication for acure headache was also monitored. Of the 98 patients in the sample, 37 were randomized to receive placebo, 6l received individualized homeopathic remedies. Groups were comparable at the beginning of the treatment. The median age was 48.5 years; 76% suffered from migraine, 51% from tension-type headaches, and 94% were previously treated for headache. The median headache frequency was 3 days a week. Headaches were present for 23 years (median). In both groups, patients showed an improvement of one headache day less per month. The use of medication for acute headache was reduced. The headache frequency of 11 patients was reduced by more than 40%. Thirty-nine patients either did not improve or experienced aggravations. There was no significant difference in any parameter between homeopathy and placebo.     

Somatic symptoms in headache patients: the influence of headache diagnosis, frequency, and comorbidity

BACKGROUND: Mood disorders of anxiety and depression are well known to be comorbid with primary headache disorders. Less is known of the comorbidity of other somatic symptoms with headache. METHODS: Headache Clinic patients were screened with the Primary Care Evaluation of Mental Disorders (PRIME-MD), a multidimensional psychiatric screening tool. The prevalence of somatic symptoms was compared by headache diagnosis, frequency of severe headache, and psychiatric diagnosis. Follow-up data were obtained 6 months after consultation. RESULTS: Clinical diagnoses and PRIME-MD data were available for 289 patients. Associated somatic symptoms were more frequent in patients with chronic migraine (mean 5.5, P<.001) and chronic daily headache (CDH) (6.3, P=.008) compared to episodic migraine (4.0); in patients with severe headache >2 days per week compared to 2 days per week had significantly higher somatic counts (P=.01). Six-month follow-up data were available for 140 patients. Associated symptoms decreased both for patients with and without decrease in severe headache frequency (mean reduction of 1.0, P=.01 and 0.8, P=.003, respectively). CONCLUSION: Associated somatic symptoms are more common in patients with chronic migraine and CDH, with more frequent severe headaches, and with associated anxiety or depression. Patients with episodic migraine have similar somatic prevalence as a previously studied primary care population. The spectrum of headache disorders may be characterized as showing increasing somatic prevalence as headaches, particularly severe headaches, become more frequent.     

Factors associated with the onset and remission of chronic daily headache in a population-based study

The etiology and prognosis of chronic daily headache (CDH) are not well understood. The aim of this study is to describe factors that predict CDH onset or remission in an adult population. Potential cases (180+ headaches per year, n=1134) and controls (two to 104 headaches per year, n=798) were interviewed two times over an average 11 months of follow-up. Factors associated with CDH prevalence at baseline were evaluated. The incidence of CDH and risk factors for onset were assessed in controls whose headache frequency increased to 180+ per year at follow-up. Prognostic factors were assessed in CDH cases whose headache frequency fell at follow-up. CDH was more common in women, in whites, and those of less education. CDH cases were more likely to be previously married (divorced, widowed, separated), obese, and report a physician diagnosis of diabetes or arthritis. At follow-up, 3% of the controls reported 180 or more headaches per year. Obesity and baseline headache frequency were significantly associated with new onset CDH. In CDH cases, the projected 1-year remission rate to less than one headache per week was 14% and to less than 180 headaches per year was 57%. A better prognosis was associated with higher education, non-white race, being married, and with diagnosed diabetes. Individuals with less than a high-school education, whites, and those who were previously married had a higher risk of CDH at baseline and reduced likelihood of remission at follow-up. New onset CDH was associated with baseline headache frequency and obesity.     

Frequency of Headaches in Children is Influenced by Headache Status in the Mother

(Headache 2010;50:973‐980) Background.— Migraine aggregates within families. Nonetheless the familial aggregation of chronic daily headaches (CDH) and of episodic headaches of different frequencies has been very poorly studied. Accordingly herein we test the hypothesis that frequency of primary headaches aggregates in the family. Methods.— Sample consisted of 1994 children (5‐12 years) identified in the population. Validated questionnaires were used to interview the parents. Crude and adjusted prevalences of low‐frequency (1‐4 headache days/month), intermediate‐frequency (5‐9 days/month), high‐frequency (10‐14 headache days/month), and CDH (15 or more headache days/month) in children were calculated as a function of headaches in the mother. Results.— Frequency of headaches in the mother predicted frequency of headaches in the children; when the mother had low frequency headaches, the children had an increased chance to have low or intermediate headache frequency (relative risk = 1.4, 1.2‐1.6) but not CDH. When the mother had CDH, risk of CDH in the children was increased by almost 13‐fold, but the risk of infrequent headaches was not increased. In multivariate models, headaches in the children were independently predicted by headaches in the mother (P < .001); headache frequency in the children was also predicted by frequency in the mother (P < .001). Conclusions.— Frequency of headaches in children is influenced by frequency of headaches in the mother and seems to aggregate in families. Future studies should focus on the determinants of headache aggregation, including genetic and non‐genetic factors.     

Treatment of migraine with pulsing electromagnetic fields: a double-blind, placebo-controlled study

The effect of exposure to pulsing electromagnetic fields on migraine activity was evaluated by having 42 subjects (34 women and 8 men), who met the International Headache Society's criteria for migraine, participate in a double-blind, placebo-controlled study. Each subject kept a 1-month, pretreatment, baseline log of headache activity prior to being randomized to having either actual or placebo pulsing electromagnetic fields applied to their inner thighs for 1 hour per day, 5 days per week, for 2 weeks. After exposure, all subjects kept the log for at least 1 follow-up month. During the first month of follow-up, 73% of those receiving actual exposure reported decreased headaches (45% good decrease, 14% excellent decrease) compared to half of those receiving the placebo (15% worse, 20% good, 0% excellent). Ten of the 22 subjects who had actual exposure received 2 additional weeks of actual exposure after their initial 1-month follow-up. All showed decreased headache activity (50% good, 38% excellent). Thirteen subjects from the actual exposure group elected not to receive additional exposure. Twelve of them showed decreased headache activity by the second month (29% good, 43% excellent). Eight of the subjects in the placebo group elected to receive 2 weeks of actual exposure after the initial 1-month follow-up with 75% showing decreased headache activity (38% good, 38% excellent). In conclusion, exposure of the inner thighs to pulsing electromagnetic fields for at least 3 weeks is an effective, short-term intervention for migraine, but not tension headaches.     

Allergy and Immunotherapy: Are They Related to Migraine Headache?

(Headache 2011;51:8‐20) Introduction.— Several studies have reported that migraine headaches are more common in patients with allergic rhinitis and that immunotherapy decreases the frequency of headache in atopic headache sufferers. Objective.— To determine if the degree of allergic sensitization and the administration of immunotherapy are associated with the prevalence, frequency, and disability of migraine headache in patients with allergic rhinitis. Methods.— Consecutive patients between the ages of 18‐65 presenting to an allergy practice that received a diagnosis of an allergic rhinitis subtype (eg, allergic or mixed rhinitis) were enrolled in this study. All participants underwent allergy testing as well as a structured verbal headache diagnostic interview to ascertain the clinical characteristics of each headache type. Those reporting headaches were later assigned a headache diagnosis by a headache specialist blinded to the rhinitis diagnosis based on 2004 International Classification Headache Disorders‐2 (ICHD‐2) diagnostic criteria. Migraine prevalence was defined as the percentage of patients with a diagnosis of migraine headache (ICHD‐2 diagnoses 1.1‐1.5). Migraine frequency represented the number of days per month with migraine headache self‐reported during the headache interview and migraine disability was the number of days with disability obtained from the Migraine Disability Assessment questionnaire. Generalized linear models were used to analyze the migraine prevalence, frequency, and disability with the degree of allergic sensitization (percentage of positive allergy tests) and administration of immunotherapy as covariates. Patients were categorized into high (> 45% positiveallergy tests) and low (≤45% positive allergy tests) atopic groups based on the number of allergy tests that were positive for the frequency and disability analyses. Results.— A total of 536 patients (60% female, mean age 40.9 years) participated in the study. The prevalence of migraine was not associated with the degree of allergic sensitization, but there was a significant age/immunotherapy interaction (P < .02). Migraine headaches were less prevalent in the immunotherapy group than the nonimmunotherapy at ages <40 years and more prevalent in the immunotherapy group at ages ≥40 years of age. In subjects ≤45 years of age, increasing percentages of allergic sensitization were associated with a decreased frequency and disability of migraine headache in the low atopic group (risk ratios [RRs] of 0.80 [95% CI; 0.65, 0.99] and 0.81[95% CI; 0.68, 0.97]) while increasing percentages were associated with an increased frequency (not disability) in the high atopic group (RR = 1.60; [95% CI; 1.11, 2.29]). In subjects ≤45 years of age, immunotherapy was associated with decreased migraine frequency and disability (RRs of 0.48 [95% CI; 0.28, 0.83] and 0.55 [95% CI; 0.35, 0.87]). In those >45 years of age, there was no effect of degree of allergic sensitization or immunotherapy on the frequency and disability of migraine headache. Conclusions.— Our study suggests that the association of allergy with migraine headaches depends upon age, degree of allergic sensitization, administration of immunotherapy, and the type of headache outcome measure that are studied. Lower “degrees of atopy” are associated with less frequent and disabling migraine headaches in younger subjects while higher degrees were associated with more frequent migraines. The administration of immunotherapy is associated with a decreased prevalence, frequency, and disability of migraine headache in younger subjects.     

Topiramate for Migraine Prevention in a Naturalistic Setting: Results From an Open Label, Flexible Dose Study

Background.— Headaches are one of the most common neurological symptoms and migraines are the most common primary headache disorder. The global prevalence of migraines is around 10% and the condition is associated with a high burden of disease. Despite an abundance of good quality evidence, only 1 in 5 of patients who fulfill the criteria for preventive migraine therapy are appropriately treated. Data on patient outcomes with preventive medication derive mostly from specialized academic centers, which contrasts with normal clinical practice where the majority of patients are treated outside tertiary care centers. Objective.— To explore tolerability, safety and efficacy outcomes of patients receiving topiramate for migraine prevention in a naturalistic setting. Methods.— After a 4‐week prospective baseline, patients with a diagnosis of migraine according to International Headache Society criteria and eligible for migraine prevention were treated with flexible dosing of topiramate for 24 weeks (core phase), and optionally for a total of 48 weeks. The primary safety analysis included adverse events (AEs) during the core phase. For the main efficacy measures, the absolute changes from baseline to end of core phase as well as last follow‐up visit were calculated for migraine days per 4 weeks, migraine attacks per 4 weeks, mean maximum visual analogue scale of migraine headache per 4 weeks and mean maximum pain intensity of migraine headache (4‐point scale) per 4 weeks. In addition, changes in individual quality of life aspects were captured. Results.— The intention‐to‐treat population (ITT) consisted of 161 patients (90.7% female, mean age 45.7 ± 11.1 years). Topiramate median dose was 45.7 mg/day at endpoint. Some 74.1% of patients reported treatment emergent AEs, most frequently paresthesias (18.4%) and nausea (12.4%). Some 20.0% of patients withdrew from the study due to AEs. The mean number of migraine days per 4 week decreased from 6.2 ± 3.9 days at baseline to 3.9 ± 3.5 days at last core visit (P < .001). Mean maximum pain intensity per 4 week changed from 7.0 ± 2.3 at baseline to 4.7 ± 3.2 at last visit core phase (P < .001). Consumption of triptans and analgesics reduced during the course of the core phase (P < .005). Fifty‐one percent of all patients experienced at least a 50% reduction in migraine days during the core phase. Conclusion.— Topiramate used for migraine prevention in non‐academic institutions is generally safe, well tolerated and results in good control of migraine headaches and improvement in several aspects of quality of life.     

The prophylactic treatment of chronic daily headache

Chronic daily headache (CDH), a heterogeneous group of headache disorders occurring on at least 15 days per month, affects up to 4% to 5% of the general population. CDH disorders include transformed (or chronic) migraine, chronic tension-type headache, new daily persistent headache, and hemicrania continua. Patients with CDH have greater disability and lower quality of life than episodic migraine patients and often overuse headache pain medications. To date, only topiramate, gabapentin, tizanidine, fluoxetine, amitriptyline, and botulinum toxin type A (BoNTA) have been evaluated as prophylactic treatment of CDH in randomized, double-blind, placebo-controlled, or active comparator-controlled trials. The evidence supporting the use of BoNTA as prophylaxis of CDH is composed of larger and longer trials, as over 1000 patients were evaluated for up to 11 months duration. Compared with placebo BoNTA has significantly reduced the frequency of headache episodes, a recommended efficacy measure for headache trials and has been demonstrated to be safe and very well tolerated with few discontinuations due to adverse events. Side effects are generally transient, mild to moderate, and nonsystemic. The results of clinical trials using traditional oral pharmacotherapy, while supportive of their use as prophylactic treatment of CDH, are limited by several factors, including small numbers of patients, the choice of efficacy measures, and short treatment periods. The use of oral agents was associated with systemic side effects, which may limit their effectiveness as prophylactic treatment of CDH.     

Headaches After Concussion in US Soldiers Returning From Iraq or Afghanistan

(Headache 2010;50:1262‐1272) Objectives.— To determine the prevalence, characteristics, impact, and treatment patterns of headaches after concussion in US Army soldiers returning from a deployment to Iraq or Afghanistan. Methods.— A cross‐sectional study was conducted with a cohort of soldiers undergoing postdeployment evaluation during a 5‐month period at the Madigan Traumatic Brain Injury Program at Ft. Lewis, WA. All soldiers screening positive for a deployment‐related concussion were given a 13‐item headache questionnaire. Results.— A total of 1033 (19.6%) of 5270 returning soldiers met criteria for a deployment‐related concussion. Among those with a concussion, 957 (97.8%) reported having headaches during the final 3 months of deployment. Posttraumatic headaches, defined as headaches beginning within 1 week after a concussion, were present in 361 (37%) soldiers. In total, 58% of posttraumatic headaches were classified as migraine. Posttraumatic headaches had a higher attack frequency than nontraumatic headaches, averaging 10 days per month. Chronic daily headache was present in 27% of soldiers with posttraumatic headache compared with 14% of soldiers with nontraumatic headache. Posttraumatic headaches interfered with duty performance in 37% of cases and caused more sick call visits compared with nontraumatic headache. In total, 78% of soldiers with posttraumatic headache used abortive medications, predominantly over‐the‐counter analgesics, and most perceived medication as effective. Conclusions.— More than 1 in 3 returning military troops who have sustained a deployment‐related concussion have headaches that meet criteria for posttraumatic headache. Migraine is the predominant headache phenotype precipitated by a concussion during military deployment. Compared with headaches not directly attributable to head trauma, posttraumatic headaches are associated with a higher frequency of headache attacks and an increased prevalence of chronic daily headache.     

Amitriptyline treatment in chronic drug-induced headache: a double-blind comparative pilot study

OBJECTIVE: To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. METHODS: Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). RESULTS: Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. CONCLUSION: This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.     

Treating chronic tension-type headache not responding to amitriptyline hydrochloride with paroxetine hydrochloride: a pilot evaluation

CONTEXT: In some individuals, chronic tension-type headache fails to respond to tricyclic antidepressant medications that often serve as first-line therapy. OBJECTIVE: To evaluate the clinical efficacy of paroxetine hydrochloride for chronic tension-type headache not responding to amitriptyline hydrochloride. DESIGN AND SETTING: Open-label trial of paroxetine conducted at 2 outpatient sites in Ohio. PARTICIPANTS AND INTERVENTION: Thirty-one adults (mean age, 37 years; 20 women) with chronic tension-type headache (mean, 25 headache days per month) who had failed to respond (less than 30% improvement) to treatment with either amitriptyline (n = 13) or matched placebo (n = 18). All participants were treated with paroxetine (up to 40 mg per day) in a 9-month protocol. OUTCOME MEASURES: Monthly headache index calculated as the mean of pain ratings (0 to 10 scale) recorded by participants in a diary 4 times per day, number of days per month with at least moderate pain (pain rating of 5 or greater), and analgesic medication use. RESULTS: In patients who had not responded to amitriptyline, paroxetine failed to reduce chronic tension-type headaches or analgesic medication use. In patients who had not responded to placebo, paroxetine produced modest reductions in chronic tension-type headaches and analgesic use. CONCLUSIONS: We found no evidence that chronic tension-type headaches that failed to respond to tricyclic antidepressant therapy with amitriptyline improved when subsequently treated with paroxetine. More support was found for the efficacy of paroxetine in patients with chronic tension-type headaches who had failed to respond to placebo.     

OnabotulinumtoxinA for Treatment of Chronic Migraine: Pooled Results From the Double‐Blind,Randomized, Placebo‐Controlled Phases of the PREEMPT Clinical Program

(Headache 2010;50:921‐936) Objective.— To assess the efficacy, safety, and tolerability of onabotulinumtoxinA (BOTOX^®) as headache prophylaxis in adults with chronic migraine. Background.— Chronic migraine is a prevalent, disabling, and undertreated neurological disorder. Few preventive treatments have been investigated and none is specifically indicated for chronic migraine. Methods.— The 2 multicenter, pivotal trials in the PREEMPT: Phase 3 REsearch Evaluating Migraine Prophylaxis Therapy clinical program each included a 24‐week randomized, double‐blind phase followed by a 32‐week open‐label phase (ClinicalTrials.gov identifiers NCT00156910, NCT00168428). Qualified patients were randomized (1:1) to onabotulinumtoxinA (155‐195 U) or placebo injections every 12 weeks. Study visits occurred every 4 weeks. These studies were identical in design (eg, inclusion/exclusion criteria, randomization, visits, double‐blind phase, open‐label phase, safety assessments, treatment), with the only exception being the designation of the primary and secondary endpoints. Therefore, the predefined pooling of the results was justified and performed to provide a complete overview of between‐group differences in efficacy, safety, and tolerability that may not have been evident in individual studies. The primary endpoint for the pooled analysis was mean change from baseline in frequency of headache days at 24 weeks. Secondary endpoints were mean change from baseline to week 24 in frequency of migraine/probable migraine days, frequency of moderate/severe headache days, total cumulative hours of headache on headache days, frequency of headache episodes, frequency of migraine/probable migraine episodes, frequency of acute headache pain medication intakes, and the proportion of patients with severe (≥60) Headache Impact Test‐6 score at week 24. Results of the pooled analyses of the 2 PREEMPT double‐blind phases are presented. Results.— A total of 1384 adults were randomized to onabotulinumtoxinA (n = 688) or placebo (n = 696). Pooled analyses demonstrated a large mean decrease from baseline in frequency of headache days, with statistically significant between‐group differences favoring onabotulinumtoxinA over placebo at week 24 (?8.4 vs ?6.6; P < .001) and at all other time points. Significant differences favoring onabotulinumtoxinA were also observed for all secondary efficacy variables at all time points, with the exception of frequency of acute headache pain medication intakes. Adverse events occurred in 62.4% of onabotulinumtoxinA patients and 51.7% of placebo patients. Most patients reported adverse events that were mild to moderate in severity and few discontinued (onabotulinumtoxinA, 3.8%; placebo, 1.2%) due to adverse events. No unexpected treatment‐related adverse events were identified. Conclusions.— The pooled PREEMPT results demonstrate that onabotulinumtoxinA is an effective prophylactic treatment for chronic migraine. OnabotulinumtoxinA resulted in significant improvements compared with placebo in multiple headache symptom measures, and significantly reduced headache‐related disability and improved functioning, vitality, and overall health‐related quality of life. Repeat treatments with onabotulinumtoxinA were safe and well tolerated.     

Migraine Education Improves Quality of Life in a Primary Care Setting

(Headache 2010;50:600‐612) Objective.— The objective of this study was to evaluate the effectiveness of the Mercy Migraine Management Program (MMMP), an educational program for physicians and patients. The primary outcome was change in headache days from baseline at 3, 6, and 12 months. Secondary outcomes were changes in migraine‐related disability and quality of life, worry about headaches, self‐efficacy for managing migraines, emergency room (ER) visits for headache, and satisfaction with headache care. Background.— Despite progress in the understanding of the pathophysiology of migraine and development of effective therapeutic agents, many practitioners and patients continue to lack the knowledge and skills to effectively manage migraine. Educational efforts have been helpful in improving the quality of care and quality of life for migraine sufferers. However, little work has been performed to evaluate these changes over a longer period of time. Also, there is a paucity of published research evaluating the influence of education about migraine management on cognitive and emotional factors (for example, self‐efficacy for managing headaches, worry about headaches). Methods.— In this open‐label, prospective study, 284 individuals with migraine (92% female, mean age = 41.6) participated in the MMMP, an educational and skills‐based program. Of the 284 who participated in the program, 228 (80%) provided data about their headache frequency, headache‐related disability (as measured by the Headache Impact Test‐6 (HIT‐6), migraine‐specific quality of life (MSQ), worry about headaches, self‐efficacy for managing headaches, ER visits for headaches, and satisfaction with care at 4 time points over 12 months (baseline, 3 months, 6 months, 12 months). Results.— Overall, 46% (106) of subjects reported a 50% or greater reduction in headache frequency. Over 12 months, patients reported fewer headaches and improvement on the HIT‐6 and MSQ (all P < .001). The improvement in headache impact and quality of life was greater among those who had more worry about their headaches at baseline. There were also significant improvements in “worry about headaches,”“self‐efficacy for managing headaches,” and “satisfaction with headache care.” Conclusion.— The findings demonstrate that patients participating in the MMMP reported improvements in their headache frequency as well as the cognitive and emotional aspects of headache management. This program was especially helpful among those with high amounts of worry about their headaches at the beginning of the program. The findings from this study are impetus for further research that will more clearly evaluate the effects of education and skill development on headache characteristics and the emotional and cognitive factors that influence headache.