Chronic daily headache in a primary care population: prevalence and headache impact test scores

BACKGROUND: Population-based surveys estimate the prevalence of chronic daily headache (CDH) in the general community to be approximately 4%. The prevalence of CDH among patients seen in the primary care setting in the United States, however, is unknown. PURPOSE: To estimate the prevalence and associated burden of suffering of CDH in a primary care patient population. METHODS: Cross-sectional survey of a randomly selected sample of 1500 adult patients in an academic Family Medicine Center was done. Outcome measures include self-reported headache frequency and Headache Impact Test scores. RESULTS: Completed questionnaires were returned by 853 (57%) patients. The mean age of respondents was 49 years (SD = 16), with a range of 18 to 94 years. Two hundred ninety-six (58%) patients reported having had 1 or more severe headaches in the past month. Seventy-four (9%) patients reported a frequency of headache consistent with CDH, defined as the occurrence of headache 15 or more days in the past month. Twenty-four patients (32%) with CDH either believed that none of their doctors know that they experienced headaches or were not sure if their doctors were aware of their headaches, and 21 (28%) reported that they have not needed a doctor's care for their headaches. CONCLUSIONS: The prevalence of CDH is greater among a primary care patient population compared to the general community. A substantial proportion of patients with CDH do not bring their headaches to the attention of their health-care providers. In light of the advances in the development of effective medications for migraines and the growing body of evidence implicating medications as a contributing cause of CDH, it may be appropriate to encourage patients to inform their health-care providers about their headaches and to encourage providers to identify patients with frequent headaches.     

Chronic daily headaches in children

Chronic daily headache (CDH) is increasingly recognized as a problem in pediatrics and tertiary pediatric headache care. It is estimated that up to 4% of the adult population has CDH. Many of these are chronic migraine (CM). The fraction of the pediatric population with CDH appears to be lower, although the prevalence has not been adequately determined. The simplest definition of CDH is more than 15 headache days per month. In the International Classification of Headache Disorders, Second Edition (ICHD-II), several types of CDH have been identified. These criteria have been contrasted with the Silberstein-Lipton criteria, with revisions suggested. The diagnosis of CDH is further complicated and may be initiated by the overuse of analgesic medications (medication overuse headache) and requires the resolution of this issue before a final diagnosis can be established. In children, most CDH appears to have migraine features, although it may not completely meet the ICHD-II criteria for migraine or CM. Evaluation of CDH needs to include a complete history and physical examination to identify any possibility of the secondary headaches or headaches directly attributed to a secondary cause. Treatment and management involve a multidisciplinary approach, including acute therapy for when the headache severity increases (while avoiding medication overuse), preventative therapy to reduce the frequency and impact of the CDH, and biobehavioral therapy to assist with long-term outcome.     

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for "red flags" that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is > or =4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review.     

Melatonin as adjunctive therapy in the prophylaxis of cluster headache: a pilot study

BACKGROUND: The periodicity of cluster headache suggests involvement of the suprachiasmatic nucleus of the hypothalamus, the biological clock. The secretion of melatonin, a hormone produced by the pineal gland and regulated by the suprachiasmatic nucleus, is altered in patients with cluster headache. Melatonin shifts circadian rhythms. A previous study of melatonin for primary prophylaxis of cluster headache demonstrated a 50% response rate. OBJECTIVE: To evaluate the use of melatonin as adjunctive therapy in patients with cluster headache who have incomplete relief of their headaches on conventional therapy. METHODS: Nine patients participated in the study, six with chronic cluster headache and three with episodic cluster headache. Patients with chronic cluster headache completed a baseline diary for 1 month, followed by 1 month of melatonin treatment, then 1 month of placebo. Patients with episodic cluster headache received placebo for 1 month, then melatonin for 1 month. Patients continued their usual prophylactic and abortive treatments during the study. Headache frequency, intensity, and use of analgesics were recorded. The primary endpoint of the study was the mean number of headaches per day, with mean daily analgesic consumption and percentage of mild, moderate, and severe headaches as secondary endpoints. RESULTS: There were no significant differences between means on analysis of variance and t testing for the melatonin, placebo, and baseline months for all primary and secondary endpoints. There were no side effects reported. CONCLUSIONS: Patients with chronic cluster headache or patients with episodic cluster headache whose headaches are uncontrolled on conventional therapy do not appear to gain therapeutically from the addition of melatonin to their usual treatment regimens. It is perhaps the phase-shifting properties of melatonin that mediate its effect in patients with episodic cluster headache, and it may be necessary to treat from the beginning of the cluster bout to reset the circadian pacemaker, thus producing a more positive outcome.     

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.     

Analysis of the patients attending a specialist UK headache clinic over a 3-year period

OBJECTIVE: This study analyzed the profile of patients who attended a specialist UK headache clinic over a 3-year period. METHODS: An audit was conducted of the clinical records of patients attending the specialist headache clinic at King's College, London, between January 1997 and January 2000. Data were collected for diagnoses given, current medications taken, medications prescribed and recommended, and investigations conducted. Results were calculated as numbers and proportions of patients for the 3-year period and for the 3 separate 12-month periods. RESULTS: A total of 458 patients were included in the audit. Most patients were diagnosed as having chronic daily headache (CDH, 60%) or migraine (33%). Prior to the clinic visit, most patients with CDH and migraine treated their headaches with analgesics, and there was little use of prophylactic medication. In the clinic, 74% of patients with CDH and 85% of migraineurs were prescribed prophylactic medication, and 81% of migraineurs were given triptans for acute treatment. Diagnostic testing was performed in 12% of the patients, and all results were normal or negative. CONCLUSIONS: CDH and migraine were the most common headache types encountered in this UK secondary-care clinic. Review of treatment patterns used prior to the initial clinic evaluation suggests that management of CDH and migraine in UK primary care is suboptimal, and educational initiatives are needed to improve headache management.     

Chronic headaches: from research to clinical practice

Chronic daily headache (CDH) is a heterogeneous group of headaches that includes primary and secondary varieties. Primary CDH is a frequent entity that probably affects 4–5% of the population. It can be subdivided into headaches of short duration (<4 h/attack) like chronic cluster headache, and disorders of long duration (>4 h/attack). Primary CDH of long duration includes transformed migraine, chronic tension–type headache, and new daily persistent headache and hemicrania continua. Analgesics, ergots and triptan overuse are frequent in all types of CDH. We revise recent insights into the epidemiology, pathophysiology, clinical characteristics and prognosis of CDH.     

Outcome of medication overuse headache after abrupt in-patient withdrawal

One hundred and one patients suffering from chronic daily headache (CDH) and medication overuse were treated, in an in-patient setting, with abrupt discontinuation of the medication overused, intravenous hydrating, and intravenous administration of benzodiazepines and ademetionine. The mean time to CDH resolution was 8.8 days. The in-patient withdrawal protocol used was effective, safe and well tolerated. There was a trend for a shorter time to CDH resolution in patients who overused triptans (P=0.062). There was no correlation between time to CDH resolution and either the type of initial primary headache or duration of medication abuse, whereas time to CDH resolution was related to daily drug intake (P=0.01). In multiple regression analysis, daily drug intake, age and type of medication overused were independent predictors of time to CDH resolution. At 3-months' follow-up, no patient had relapsed and was again overusing symptomatic medications.     

Chronic daily headache in a paediatric headache centre

The prevalence and the clinical features of chronic daily headache (CDH) were studied in 968 children and adolescents observed during a period of one year in the Headache Centre of the Anna Meyer Paediatric Hospital of Florence. Nine hundred and fortyfour patients (97.52%) had primary headache according to ICHD-II, 24 subjects had secondary headache and 56 patients had CDH (5.93% of primary headaches). The mean age of subjects with CDH was higher than general (13.5 vs. 11.5 years), with a female preponderance (69.6% vs. 30.4%). According to the ICHD-II, headaches were classified as chronic migraine in 10 patients (1.5.2 ICHD-II), chronic tension-type headache in 36 (2.3 ICHD-II), new daily persistent headache in 8 (4.8 ICHD-II) and 2 patients reported mixed pattern (chronic migraine+chronic tension type headache). Medication overuse was not implicated in our patients.     

Treatment of chronic daily headache

Patients with chronic daily headache (CDH) are difficult to treat. A combination of general measures and specific pharmacological treatments is necessary. When possible, pharmacological management should be planned on an outpatient basis. The general protocol should include abrupt discontinuation of the offending symptomatic medications, specific treatment for detoxification, daily nonsteroidal anti-inflammatory drugs (NSAIDs) for about 1 month, triptans only for moderate-severe headache, and prophylactic treatment. Either amitriptyline plus propranolol or valproic acid have been classically recommended for transformed migraine prophylaxis. Refractory patients can respond to a combination of a beta-blocker and valproic acid, possibly due to their complementary mechanisms of action. Recently, the new antiepileptic topiramate has been shown to be especially useful in this indication. At least one-third of patients, however, do not improve. Therefore, the best treatment of this incapacitating entity continues to be its prevention. Preventive measures should include: (1) public information concerning the risk of frequent self-treatment for headaches; (2) inform headache patients of the risk of analgesic overuse/rebound headache; (3) recommend NSAIDs and triptans as symptomatic medications; and (4) active use of preventive medications when headaches begin to increase in frequency.     

Chronic daily headaches: clinical profile in Indian patients

Chronic daily headache (CDH) remains a relatively unexplored entity in India. Misconceptions are common, unnecessary investigations often done and inappropriate therapy prescribed. Analgesic overuse is seldom recognized. The present report appears to be the first of its kind from India. CDH has been defined as headaches occurring more than 15 days per month for more than 3 months (secondary causes excluded). Over 2 years (1998-1999) 849 cases (49.6% of all primary headaches) were seen. More than 1 year's follow-up data were available in 205 subjects (M 34; F 171). The distribution of these was as follows: (i), chronic tension-type headache (CTH), 33 (16.1%); (ii), chronic/transformed migraine (TM), 169 (82.4%); (iii), new persistent CDH, 3 (1.5%). There were 169 cases of TM (M : F 1 : 4.7; age 26-58 years). History of past episodic migraine was present in all. Transformation had been gradual (89.4%) or acute (10.6%). Possible factors in transformation included psychological stress (44.4%), analgesic overuse (28.4%), ergot overuse (4.1%). HRT seemed to be implicated in three female subjects. Analgesic overuse was limited between intake of 600 and 2400 mg of aspirin equivalent per day (mean 735 mg). Ergot overuse varied between 1 and 3 mg/day of ergotamine for > or = 3 days/week. With medical therapy approximately 70% TM and 40% CTH patients noted significant improvement. About 80% of these relapsed on therapy withdrawal. CDH in India is not uncommon. Analgesic/ergot overuse needs to be recognized early. The average dose of analgesic implicated in CDH seems much less compared with that reported in the West.     

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.     

Chronic daily headache in children and adolescents: a clinic based study from India

Chronic Daily Headache (CDH) is uncommon in Indian children compared to their adult counterpart. This is a retrospective study looking at the headache phenomenology of CDH in Indian children and adolescents. The validity of the case definitions of subtypes of chronic primary headaches mentioned in the IHS 2004 classification have been evaluated. 22 children (age range 8-15 years; M : F-16 : 6) diagnosed as having primary CDH using a modified definition seen between 2002 and 2003 have been studied. CDH has been defined as daily or near daily headaches > 15d/month for > 6 weeks. The rationale for this modified definition has been discussed. Majority of children (15/22) had a more or loss specified time of onset of regular headache spells resembling New Daily Persistent Headache (NDPH) but did not fulfil totally the diagnostic criteria of NDPH as laid down by IHS 2004. In all cases headache phenomenology included a significant vascular component. Headache phenomenology closely resembled Chronic Tension Type Headache (CTTH) in 4 patients and Chronic Migraine in 3 patients. However, in no patient in these groups, a history of evolution from the episodic forms of the diseases could be elicited. Heightened level of anxiety mostly related to academic stress and achievement was noted in the majority (19/22). Only a minority of patients (3/22) had anxiety and depression related to interpersonal relationships in the family. Medication overuse was not implicated in any patient. CDH in children in India is very much different from CDH in adults with the vast majority of patients exhibiting overlapping features of migraine and tension-type headache. There is need for a modified diagnostic criteria and terminology for chronic primary headaches in children.     

Primary headaches in HIV-infected patients

Headache in patients with human immunodeficiency virus (HIV) infection may indicate life-threatening illnesses such as opportunistic infections or neoplasms. Alternatively, such patients may develop benign self-limiting headaches. Hence, defining the various types of headache in these patients is essential for proper management. This study describes the clinical characteristics of primary headaches occurring in a group of HIV-infected patients. Of 115 patients seen from 1990 to 1996, 44 (38%) had headaches. Primary headaches were present in 29 (66%) patients and secondary causes were identified in 15 (34%). Among those with primary headaches, migraine occurred in 22 (76%), tension-type headache in 4 (14%), and cluster headache in 3 (10%) patients. Half of those with migraine (n=ll), 1 patient with tension-type headache, and 1 patient with cluster headache developed chronic daily headaches which were severe and refractory to conventional headache or antiretroviral therapy. We conclude that primary headaches in patients with HIV infection are: (1) the commonest type of headache; (2) may present for the first time in individuals with severe immunosuppression; (3) usually bear no relationship to antiretroviral drug therapy; (4) polypharmacy, depression, anxiety, and insomnia are commonly associated comorbidities; (5) frequently do not respond to conventional management and carry a poor prognosis; and (6) do not require neuroradiological and/or cerebrospinal fluid evaluations.     

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.     

Headache profiles in patients with a dilatated cyst of the cavum septi pellucidi

The dilatated cyst of the cavum septi pellucidi (CSP) is rare and may be associated with headaches. We reviewed the computerized database of 54,000 patients' computed tomography or magnetic resonance images and found 22 cases (0.04%) involving a dilatated cyst of the CSP. Sixteen patients had a chief complaint of headache, which was classified as acute episodic headache (type I, n = 7, 43.7%), chronic daily headache (CDH) with acute onset (type II, n = 5, 31.3%), or CDH with insidious onset (type III, n = 4, 25%). Acute Valsalva-induced headaches were common with type I (85%) or II (100%); 70% of these responded to indomethacin. At follow-up, patients with type I headache had the highest remission rate (71%), and type III patients the lowest (0%). Dilatated cysts of the CSP should be considered a cause of acute Valsalva-induced headache or new daily persistent headache, and may respond to indomethacin. A protracted course (> or = 3 months) indicates a worse outcome.     

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.     

Management of primary chronic headache in the general population: the Akershus study of chronic headache

Primary chronic headaches cause more disability and necessitate high utilisation of health care. Our knowledge is based on selected populations, while information from the general population is largely lacking. An age and gender-stratified cross-sectional epidemiological survey included 30,000 persons aged 30–44 years. Respondents with self-reported chronic headache were interviewed by physicians. The International Classification of Headache Disorders was used. Of all primary chronic headache sufferers, 80% had consulted their general practitioner (GP), of these 19% had also consulted a neurologist and 4% had been hospitalised. Co-occurrence of migraine increased the probability of contact with a physician. A high Severity of Dependence Scale score increased the probability for contact with a physician. Complementary and alternative medicine (CAM) was used by 62%, most often physiotherapy, acupuncture and chiropractic. Contact with a physician increased the probability of use of CAM. Acute headache medications were taken by 87%, while only 3% used prophylactic medication. GPs manage the majority of those with primary chronic headache, 1/5 never consults a physician for their headache, while approximately 1/5 is referred to a neurologist or hospitalised. Acute headache medication was frequently overused, while prophylactic medication was rarely used. Thus, avoidance of acute headache medication overuse and increased use of prophylactic medication may improve the management of primary chronic headaches in the future.     

An expert system for headache diagnosis: the Computerized Headache Assessment tool (CHAT)

BACKGROUND: Migraine is a highly prevalent chronic disorder associated with significant morbidity. Chronic daily headache syndromes, while less common, are less likely to be recognized, and impair quality of life to an even greater extent than episodic migraine. A variety of screening and diagnostic tools for migraine have been proposed and studied. Few investigators have developed and evaluated computerized programs to diagnose headache. OBJECTIVES: To develop and determine the accuracy and utility of a computerized headache assessment tool (CHAT). CHAT was designed to identify all of the major primary headache disorders, distinguish daily from episodic types, and recognize medication overuse. METHODS: CHAT was developed using an expert systems approach to headache diagnosis, with initial branch points determined by headache frequency and duration. Appropriate clinical criteria are presented relevant to brief and longer-lasting headaches. CHAT was posted on a web site using Microsoft active server pages and a SQL-server database server. A convenience sample of patients who presented to the adult urgent care department with headache, and patients in a family practice waiting room, were solicited to participate. Those who completed the on-line questionnaire were contacted for a diagnostic interview. RESULTS: One hundred thirty-five patients completed CHAT and 117 completed a diagnostic interview. CHAT correctly identified 35/35 (100%) patients with episodic migraine and 42/49 (85.7%) of patients with transformed migraine. CHAT also correctly identified 11/11 patients with chronic tension-type headache, 2/2 with episodic tension-type headache, and 1/1 with episodic cluster headache. Medication overuse was correctly recognized in 43/52 (82.7%). The most common misdiagnoses by CHAT were seen in patients with transformed migraine or new daily persistent headache. Fifty patients were referred to their primary care physician and 62 to the headache clinic. Of 29 patients referred to the PCP with a confirmed diagnosis of migraine, 25 made a follow-up appointment, the PCP diagnosed migraine in 19, and initiated migraine-specific therapy or prophylaxis in 17. CONCLUSION: The described expert system displays high diagnostic accuracy for migraine and other primary headache disorders, including daily headache syndromes and medication overuse. As part of a disease management program, CHAT led to patients receiving appropriate diagnoses and therapy. Limitations of the system include patient willingness to utilize the program, introducing such a process into the culture of medical care, and the difficult distinction of transformed migraine.     

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.