An open-label dose-titration study of the efficacy and tolerability of tizanidine hydrochloride tablets in the prophylaxis of chronic daily headache

OBJECTIVE: To assess effectiveness and safety of tizanidine hydrochloride tablets for the prophylaxis of chronic daily headache. BACKGROUND: Tizanidine hydrochloride is an alpha2-adrenergic agonist that inhibits the release and effectiveness of norepinephrine at both central sites (eg, the locus ceruleus) and the spinal cord. It acts as a central muscle relaxant and has antinociceptive effects. Preliminary research and retrospective analyses have suggested efficacy in treatment of both chronic tension-type headache and chronic daily headache with migrainous features. DESIGN: Thirty-nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed a 4-week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over three doses per day) by treatment week 4. RESULTS: The overall headache index through week 12 (headache frequency x average intensity x duration) declined significantly (P<.00000002), with a corresponding increase in mean percentage improvement from 49% for weeks 1 through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12 (P<.0182). During weeks 9 through 12, 67% had improved more than 50% compared to baseline. Overall headache frequency declined from 22.83 to 15.83 days per month (P<.00001), with frequency of severe headaches dropping from 7.52 to 3.58 days per month (P<.000035). Average headache intensity dropped from 1.83 to 1.07 (1-to-5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was reduced from 6.96 to 4.00 hours per headache (P<.00001). Improvement also occurred on visual analog scales of overall headache status, mood, sleep, quality of life (P<.00001), and sexual function (P<.0075); as well as the Beck Depression Inventory-II (P<.00073). Mild-to-moderate adverse events reported by more than 10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients discontinued treatment due to adverse events: somnolence and dry mouth alone (n = 1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1). One patient had elevated liver enzymes that returned to normal after the drug was discontinued. CONCLUSIONS: The results provide preliminary support for the efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic daily headache.     

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.     

Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases

OBJECTIVE: To review the efficacy of naratriptan as preventive treatment in 27 patients with chronic migraine refractory to other commonly used preventive therapies. BACKGROUND: The treatment of chronic migraine often poses a major challenge to the clinician. Even when given expert care, patients with chronic migraine may continue to have daily or near-daily headaches. METHODS: Clinical records and headache calendars were reviewed of 27 patients fulfilling the following inclusion criteria: (1) aged 18 to 65 years; (2) diagnosis of chronic migraine (formerly transformed migraine), according to the criteria proposed by Silberstein et al; (3) previous failure of at least 4 preventive medications prescribed as part of a management program that included nonpharmacological measures, preventive medication, acute care medication, and detoxification from overused medication; and (4) have used daily naratriptan for no less than 2 consecutive months. The dose of naratriptan prescribed was 2.5 mg twice daily. We considered the following outcomes: (1) frequency of headache, (2) intensity of pain, (3) number of days per month with severe headache, (4) headache index (frequency times intensity), and (5) proportion of patients who reverted to an episodic pattern of pain after 6 months of treatment. RESULTS: There was a statistically significant reduction in the frequency of headache days 2 months (15.3 days versus 24.1 days at baseline, P<.001), 6 months (9.1 days, P<.001), and 1 year (7.3 days, P<.001) after daily treatment with naratriptan was initiated. There was also a statistically significant reduction in the number of days per month of severe pain at 1 month (5.6 days versus 12.5 days at baseline, P<.01), 2 months (5.7 days, P<.01), 6 months (2.8 days, P<.01), and 1 year (2.6 days, P<.01). Similarly, there was a statistically significant reduction in the headache index at 2 months (33 versus 56.4 at baseline, P<.001), 6 months (19.5, P<.001), and 1 year (17.2, P<.001). Of the 20 patients who continued to use naratriptan daily for at least 6 months, 13 (65%) reverted to an episodic pattern of pain (migraine). At 1 year, 11 (55%) still continued to experience episodic headache, 1 (5%) relapsed to chronic migraine, and 2 (10%) were lost to follow-up. No patients had intolerability to naratriptan during the treatment period, and no one stopped treatment due to adverse events. CONCLUSIONS: Naratriptan may have a role in the preventive treatment of intractable chronic migraine. Prospective, controlled studies should be considered.     

Classification of chronic daily headache by International Headache Society criteria: limits and new proposals

We conducted a retrospective study of 150 patients with chronic daily headache (CDH) to determine how to categorize their headache according to the classification of the International Headache Society (IHS). All patients were first evaluated at Parma and Pavia Headache Centres (from January 1992 to March 1993) and had had headache for at least 15 days a month during the previous 6 months. Four patients were thereafter excluded due to poor reliability. The 146 patients who met our CDH criteria (92 with and 54 without clear-cut migraine attacks) could be classified into four groups: (i) chronic tension-type headache (CTTH)-27 patients; (ii) coexisting migraine plus CTTH-65 patients; (iii) unclassifiable daily headache-27 patients; and (iv) migraine and an unclassifiable interval headache-27 patients. Seventy-two percent of patients with CDH had migraine as the initial form of their headache. We therefore propose to revise the IHS classification for migraine, taking into account its evolution, and add two subcategories, migraine with interparoxysmal headache and chronic migraine.     

Depression scores following migraine treatment in patients attending a specialized center for headache and neurology

OBJECTIVE: To determine the changes in clinical characteristics and depression levels among patients following treatment for migraine. BACKGROUND: Epidemiologic studies have provided consistent evidence regarding an association between migraine and depression. In Puerto Rico, however, migraine has not yet been systematically investigated. METHODS: A chart review of 144 Puerto Rican patients who presented with migraine, diagnosed according to the International Headache Society criteria, and depression over a 2-year period was performed. The level of depression, before and after migraine treatment, was evaluated using the Zung Self-rating Depression Scale. RESULTS: The mean age of patients was 37.0 +/- 14.4 years; 77.1% were women. More than half (52.8%) reported severe headache and 56.9% reported a monthly frequency of five attacks or more. Nearly 9% were using antidepressant therapy and 8% were under psychiatric treatment. The mean Zung index score at baseline was 50.6 +/- 10.9. Following treatment with triptans, the intensity and frequency of migraine and the Zung index score decreased significantly (P<.00001). A trend for a greater reduction in Zung index scores among patients receiving triptan medications for more than a year was demonstrated (P =.07). CONCLUSIONS: These results indicate that migraine treatment with triptans appears to be effective in decreasing the headache frequency and intensity, and depression levels, independent of antidepressant medication use or psychiatric treatment.     

The course of migraine—a diary study in unselected patients

The course of disease and the predictive value of depression and anxiety in patients with migraine were prospectively examined. We recruited 393 migraineurs through articles in newspapers and performed a follow-up examination 30 months later. At baseline and follow-up, patients underwent a semistructured interview, filled out the Headache Impact Test (HIT-6), Self-rating Depression Scale (SDS) and Self-rating Anxiety Scale (SAS) and they kept a headache diary for 30 days. One hundred and fifty-one patients (38.6%) were seen at follow-up. The baseline data of patients with and without follow-up were comparable. At follow-up the number of headache days per month had decreased from 9.6 ± 5.8 to 8.1 ± 6.3 ( P  < 0.001) and the proportion of patients with chronic headache (15.4%) and medication overuse (13%) had remained stable. SDS and SAS scores were associated with a high migraine frequency and high initial SDS scores predicted high migraine frequency at follow-up. This longitudinal study in unselected patients with migraine not excluding subjects with chronic headache, medication overuse, depression or anxiety does not point towards migraine as a progressive disease in the vast majority of patients and confirms the importance of psychiatric comorbidity.     

Childhood Maltreatment and Migraine (Part II). Emotional Abuse as a Risk Factor for Headache Chronification

(Headache 2010;50:32‐41) Objectives.— To assess in a headache clinic population the relationship of childhood abuse and neglect with migraine characteristics, including type, frequency, disability, allodynia, and age of migraine onset. Background.— Childhood maltreatment is highly prevalent and has been associated with recurrent headache. Maltreatment is associated with many of the same risk factors for migraine chronification, including depression and anxiety, female sex, substance abuse, and obesity. Methods.— Electronic surveys were completed by patients seeking treatment in headache clinics at 11 centers across the United States and Canada. Physician‐determined data for all participants included the primary headache diagnoses based on the International Classification of Headache Disorders‐2 criteria, average monthly headache frequency, whether headaches transformed from episodic to chronic, and if headaches were continuous. Analysis includes all persons with migraine with aura, and migraine without aura. Questionnaire collected information on demographics, social history, age at onset of headaches, migraine‐associated allodynic symptoms, headache‐related disability (The Headache Impact Test‐6), current depression (The Patient Health Questionnaire‐9), and current anxiety (The Beck Anxiety Inventory). History and severity of childhood (<18 years) abuse (sexual, emotional, and physical) and neglect (emotional and physical) was gathered using the Childhood Trauma Questionnaire. Results.— A total of 1348 migraineurs (88% women) were included (mean age 41 years). Diagnosis of migraine with aura was recorded in 40% and chronic headache (≥15 days/month) was reported by 34%. Transformation from episodic to chronic was reported by 26%. Prevalence of current depression was 28% and anxiety was 56%. Childhood maltreatment was reported as follows: physical abuse 21%, sexual abuse 25%, emotional abuse 38%, physical neglect 22%, and emotional neglect 38%. In univariate analyses, physical abuse and emotional abuse and neglect were significantly associated with chronic migraine and transformed migraine. Emotional abuse was also associated with continuous daily headache, severe headache‐related disability, and migraine‐associated allodynia. After adjusting for sociodemographic factors and current depression and anxiety, there remained an association between emotional abuse in childhood and both chronic (odds ratio [OR] = 1.77, 95% confidence intervals [CI]: 1.19‐2.62) and transformed migraine (OR = 1.89, 95% CI: 1.25‐2.85). Childhood emotional abuse was also associated with younger median age of headache onset (16 years vs 19 years, P = .0002). Conclusion.— Our findings suggest that physical abuse, emotional abuse, and emotional neglect may be risk factors for development of chronic headache, including transformed migraine. The association of maltreatment and headache frequency appears to be independent of depression and anxiety, which are related to both childhood abuse and chronic daily headache. The finding that emotional abuse was associated with an earlier age of migraine onset may have implications for the role of stress responses in migraine pathophysiology.     

Botulinum toxin type A as an effective prophylactic treatment in primary headache disorders

OBJECTIVE: To measure the effect of botulinum toxin type A (Botox, Allergan, Inc, Irvine, CA) treatment in 271 patients diagnosed with headache in accordance with International Headache Society (IHS) criteria. BACKGROUND: Botulinum toxin type A has shown promise for the treatment of headache in several clinical trials, but uncertainty remains as to how botulinum toxin type A optimally should be used for treating headache and which patients are best suited for this treatment. METHODS: This was a retrospective chart review of all patients who received botulinum toxin type A for the treatment of headache from January 1999 to February 2002. Patients were injected with an average dose of 63.2 U (SD, 14.5) of botulinum toxin type A on 2 or more visits, with treatments involving a "fixed-site" or a "follow-the-pain" (or a combination of both) approach. In the fixed-site approach, botulinum toxin type A was injected into the procerus, corrugator, frontalis, and temporalis muscles. In the follow-the-pain approach, botulinum toxin type A was injected into a combination of the procerus, corrugator, frontalis, temporalis, occipitalis, trapezius, and/or semispinalis capitis muscles. The primary outcomes for the trial were the reduction in headache days per month or headache intensity (0 to 3 scale) (or both) from baseline. Patients were diagnosed according to IHS criteria and subsequently classified into the following categories: chronic daily headache (more than 15 headache days per month), episodic tension-type headache, episodic migraine, and "mixed" HA (less than 15 headache days per month, combination of migraine and tension-type headache). RESULTS: Treatment period was an average of 8.6 months (SD, 6.4); patients received an average of 3.4 doses (SD, 1.6) 3 months apart. Of the 271 patients, 29 (10.7%) had episodic migraine, 17 (6.3%) had episodic tension-type headache, 71 (26.2%) had mixed headache, and 154 (56.8%) had chronic daily headache. Two-hundred fifty-six patients had data for the number of headache days per month, 117 had data for headache intensity, and all 271 had data for headache days or headache intensity. Botulinum toxin type A treatment significantly reduced the number of headache days per month from 18.9 (SD, 10.3) to 8.3 (SD, 8.9) (n=256, P<.001)--a 56% reduction. Headache intensity decreased from 2.4 points (SD, 0.6) to 1.8 points (SD, 0.8) (n=117, P<.001)--a 25% reduction. Of 263 patients surveyed, 225 (85.6%) reported improvement in headache frequency and intensity. There was no correlation of effect/lack of effect with reason for treatment, duration/number of treatments, injection technique, mean/total dose, age, gender, or comorbidity. Approximately 95% of patients did not experience medication side effects. CONCLUSION: These results suggest that botulinum toxin type A may be an effective and safe prophylactic treatment for a variety of moderate to severe chronic headache types.     

Daily sumatriptan for detoxification from rebound

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

Comorbidity of headaches and depression in the elderly.

The comorbidity of headache and depression is rarely studied in the elderly. Confounders were seldom controlled in previous studies. From August 1993 to March 1994, we conducted a door-to-door survey to investigate the relationship of headache and depression in a Chinese elderly population (age > or = 65 years old) in two townships of Kinmen, Taiwan. A total of 1421 participants (71%) out of 2003 eligible citizens completed five measurements: a structured headache interview, Geriatric Depression Scale-short form (GDS-S), a survey of chronic medical illness. Cognitive Abilities Screening Instrument and an evaluation of activities of daily living. Headache diagnoses were made according to the criteria of the International Headache Society (IHS), 1988. Depression was defined as a GDS-S score > or = 8. After adjustment for confounding, subjects with more frequent headaches, more severe headaches, diagnoses of IHS migraine or chronic tension-type headaches in the past year, or a lifetime history of any headache including migraine were more likely to be depressed. In addition, the most relevant headache-related predictors of depression were the presence of any reported lifetime headache (odds ratio (OR) = 1.8, P < 0.01) and headache frequency > or = 7 days/month in the past year (OR = 2.0, P = 0.01). This study provided evidence that headache is independently associated with depression in the elderly. A high comorbidity of depression was found in the elderly with IHS migraine or chronic tension-type headaches. Not only the headache profile in the past year but also that in their lifetime was important in predicting current depression in the elderly. 1     

Central 5-HT receptor hypersensitivity in migraine without aura

Serotonin has long been implicated as a key neurotransmitter in migraine. There is a dearth of research specifically examining 5-HT1A receptor sensitivity in migraine despite the importance of this receptor in regulating central serotonergic tone. In this study we examined the hypothesis that migraine without aura is associated with hypersensitivity of central 5-HT1A receptors, using a 5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses between a test group with migraine and a matched group of healthy controls. Twelve female subjects fulfilling International Headache Society (IHS) criteria for migraine without aura were evaluated. Following an overnight fast, subjects presented for testing at 9am. An intravenous canula was inserted and serum prolactin was assessed at baseline and every 30 min for 3 h following a single dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed during the first 5 days of the menstrual cycle. No subjects were taking psychotropic medication or migraine prophylactic treatment. Patients with current or previous psychiatric disorder, daily headache or analgesic overuse were excluded. 16 healthy female volunteers matched for age and menstrual status were also evaluated and served as controls. There was no difference in baseline prolactin between groups. There was a significant rise in prolactin following buspirone in both groups. Subjects with migraine had a significantly increased prolactin response to buspirone (delta max) compared to controls (P < 0.001). This study supports the hypothesis that migraine without aura is associated with a relative hypersensitivity of central 5-HT1A receptors. This is of relevance given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the possible association between migraine and anxiety and depression.     

Assessment of migraine disability using the migraine disability assessment (MIDAS) questionnaire: a comparison of chronic migraine with episodic migraine

BACKGROUND: Chronic migraine is the most common type of chronic daily headache seen in headache tertiary care centers. Most patients with chronic migraine report their ability to function and feeling of well-being as severely impaired. OBJECTIVE: To measure the headache-related disability of patients with chronic migraine using the Migraine Disability Assessment (MIDAS) Questionnaire, comparing it with that obtained in a control group of patients with episodic migraine. METHODS: The clinical records of 703 patients with chronic daily headache treated in a headache specialty clinic were reviewed to identify 182 with chronic migraine who were evaluated using the MIDAS at their initial visit. Our control group consisted of 86 patients with episodic migraine. RESULTS: Of the 182 patients with chronic migraine, 127 (69.8%) were overusing acute-care medication. Patients were predominantly women (72.5%), with a mean age of 38.3 years. The group with episodic migraine consisted of 59 women (68.6%), with a mean age of 36.1 years. No statistically significant demographic differences were observed between the two groups. The group with chronic migraine had more total headache days over 3 months (66.7 versus 15.5, P<.001), missed more days of work or school (5.3 versus 2.3, P =.0007), had more reduced effectiveness days at work or school (11.9 versus 4.6, P =.0001), missed more days of housework (16.5 versus 3.3, P<.0001), and missed more days of family, social, or leisure activities (7.0 versus 5.5, P =.03). The group with chronic migraine was more likely to be in MIDAS grade IV (64.3% versus 43.2%, P =.001), reflecting the great likelihood of severe disability in this group. The average total MIDAS score was 34.9 in the group with chronic migraine versus 19.3 in the group with episodic migraine (P<.001). CONCLUSION: In subspecialty centers, patients with chronic migraine demonstrate remarkable impairment of their daily activities and are severely burdened by their headache syndrome, reflected by their high MIDAS scores. The chronicity and pervasiveness of migraine thus is associated with increased functional impairment as well as increase in headache frequency.     

Amitriptyline versus amitriptyline combined with fluoxetine in the preventative treatment of transformed migraine: a double-blind study

BACKGROUND AND OBJECTIVES: Antidepressants are often used to treat chronic daily headache disorders such as transformed migraine, in part because of the high prevalence of associated mood disorder. We conducted this study to evaluate the efficacy and tolerability of combined treatment with amitriptyline and fluoxetine compared with amitriptyline alone for chronic daily headache due to transformed migraine. PATIENTS AND METHODS: Thirty-nine patients, 26 women and 13 men, aged 20 to 69 years (mean, 36.4; SD, 2.5) who fulfilled criteria for transformed migraine proposed by Silberstein et al were studied prospectively. Amitriptyline was dosed as follows: 8 mg/day for 6 days, 8 mg twice a day for 6 days, 20 mg/day for 6 days, and 20 mg twice a day for 45 days. In the group receiving combination therapy, fluoxetine was dosed and administered identically. The initial and end of the study (9 weeks) headache indices (frequency x intensity) were compared between groups. RESULTS: Twenty-seven patients completed the study, 13 in the amitriptyline-alone group (group 1) and 14 in the combination-therapy group (group 2). The most frequent adverse event in both groups was dry mouth, and there was no significant difference in the occurrence of this or other adverse events between the two groups. Initial headache indices were similar for groups 1 and 2. The mean difference between the initial and final headache index for group 1 was 513.5 (P<.0005) and 893 (P<.0017) for group 2. The difference between the final headache index for the two groups was not significant (P>.207). CONCLUSIONS: We were unable to demonstrate any significant benefit from amitriptyline plus fluoxetine over amitriptyline alone in the treatment of chronic daily headache/transformed migraine. Because of the small number of subjects involved and the short duration of our study, a type II error cannot be excluded.     

Rapid and sensitive paradigm for screening patients with headache in primary care settings

OBJECTIVE: To determine the sensitivity and specificity of a brief headache screening paradigm for primary care clinicians. BACKGROUND: Migraine and drug rebound headache are disabling primary headache disorders. Both are underdiagnosed and undertreated. A method for rapid screening of migraine, drug rebound headache, and other daily headache syndromes would be useful. The Brief Headache Screen uses 3 questions-the frequency of severe (disabling) headache, other (mild) headache, and use of symptomatic medication-to generate diagnoses. METHODS: The Brief Headache Screen was evaluated in an emergency department, a family practice department, and a referral headache clinic. Diagnoses from the Brief Headache Screen were compared to diagnoses of trained researchers and headache specialists. RESULTS: Three hundred ninety-nine patients were screened and interviewed. The criterion of episodic severe (disabling) headache correctly identified migraine in 136 (93%) of 146 patients with episodic migraine and 154 (78%) of 197 patients with chronic migraine, with a specificity for any migraine (episodic or chronic) of 32 (63%) of 51. The inclusion of episodic or daily severe headache identified migraine in 100% of patients with chronic migraine. Only 6 (1.7%) of 343 patients with migraine were not identified by severe (disabling) headache. The combination of severe and mild headache frequency was sensitive to daily headache syndromes in 218 (94%) of 232 patients with a specificity of 87 (54%) of 162. Medication overuse was correctly identified in 146 (86%) of 169 patients with a specificity of 22 (79%) of 28. CONCLUSIONS: The frequency of severe (disabling) and mild headaches and use of symptomatic medications, rapidly and sensitively screens for migraine, daily headache syndromes, and medication overuse. The use of this paradigm in primary care settings may improve the recognition of these important headache syndromes.     

Chronic daily headache in the absence of medication overuse: Is daily or continuous pain more treatment-resistant than chronic daily headache with pain-free days?

To our patients, their families, and treatment providers who may not be headache specialists, chronic daily headache (CDH) would appear to refer to headache disorders marked by the presence of daily pain over an extended period of time. To the headache specialist, in contrast, CDH represents a family of headache disorders in which pain occurs from 15 to 30 days each month [1], now reflected in the International Headache Society (IHS) criteria for chronic migraine (CM) or chronic tension-type headache [2]. The IHS classification does not distinguish between daily CM and intermittent CM marked by at least some pain-free days [3]. Research studies and clinical reports of the diagnostic entities subsumed under CDH often include patients with pain-free days and those with true daily pain.     

Factors associated with burden of primary headache in a specialty clinic

OBJECTIVE: To examine factors associated with social, occupational, and psychological burden of common primary headache (migraine and tension-type headache). BACKGROUND: The personal and social burden of primary headache is high. Health, occupational, social, and psychological factors contributing to burden in people with disabling headache have not been fully unravelled. METHODS: One hundred eighty consecutive patients with either migraine or tension-type headache attending a specialty headache outpatient clinic for the first time were evaluated over a 9-month period. Headache subtype was operationally defined according to International Headache Society criteria. Headache frequency, duration, and severity were recorded. Occupational and social disability were quantified using the Migraine Disability Assessment questionnaire. Psychological burden was quantified using the 28-item General Health Questionnaire, the Beck Depression Inventory, and the State-Trait Anxiety Inventory. Premorbid vulnerability to life stress was quantified using the neuroticism subscale of the Eysenck Personality Inventory. RESULTS: Patients with frequent (chronic) headache scored higher on the Migraine Disability Assessment questionnaire and had higher Beck Depression Inventory and General Health Questionnaire depression scores than those with less frequent (episodic) headache. Frequency of headache, but not pain severity, duration, or diagnosis, predicted both Migraine Disability Assessment total disability and General Health Questionnaire/Beck Depression Inventory depression. Neuroticism was predictive of depression but not disability. Patients with chronic migraine had the highest depression and disability scores. CONCLUSION: The number of days per month with headache is a key determinant of headache-related burden in those attending specialty clinics. Frequent (chronic) headache is associated with significantly higher psychopathology scores and general social impairment, but the direction of this relationship is not clear. Those with migraine and chronicity are the most impaired.     

Divalproex ER Prophylaxis in Migraineurs with Probable Chronic Migraine and Probable Medication-Overuse Headache: A Case Series

Abstract:   This case series prospectively evaluated divalproex ER in 15 headache clinic migraine patients fulfilling International Headache Society criteria for probable chronic migraine and probable medication-overuse headache. Divalproex ER was initiated at 500 mg QHS and increased after Week 2 to 1000 mg QHS for a total treatment period of 2 months. Mean headache days per month dropped from 21.6 to 10.4 at month 1 and 8.9 at month 2. All 10 patients who completed the study rated their satisfaction with treatment as changed from unsatisfied at baseline to satisfied at study completion. The results of this study support the prophylactic efficacy of divalproex ER in migraine patients with probable chronic migraine and probable medication-overuse headache.     

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.     

Duration of migraine is a predictor for response to botulinum toxin type A

OBJECTIVE: To identify the clinical characteristics and/or injection parameters that predict a favorable response to botulinum toxin type A in patients with episodic and chronic migraine. BACKGROUND: There is emerging scientific and clinical evidence to support the utility of botulinum toxin type A (BoNT-A) in the prophylaxis of episodic and chronic migraine headache. However, the patient characteristics and injection strategies that predict a favorable treatment response are unknown. METHODS: We conducted a prospective, open-label study on 74 patients from our clinic receiving BoNT-A for episodic or chronic migraine. For all patients, migraine-related disability (Migraine Disability Assesment [MIDAS]), headache frequency, and average headache intensity were obtained at baseline and at 3 months post-BoNT-A. Information regarding demographic characteristics and injection parameters was also collected. RESULTS: Sixty-one patients met the study criteria and were available for 3-month follow-up. At the 3-month follow-up visit, the mean MIDAS scores of the 61 qualified study patients had decreased from 102 at baseline to 49 (52% decrease, P<.001). The mean number of headache days was reduced from 60 to 39 (P<.001), and the mean headache intensity decreased from 7.6 at baseline to 5.9 (P<.001). Frequency of migraine attacks, presence of analgesic overuse, total BoNT-A dose, and presence of underlying muscle tenderness were not predictive of treatment response. Age and duration of migraine were the only clinical factors significantly predictive of treatment response. Age likely was a predictor only as a consequence of duration of illness as subjects with migraine duration greater than 30 years were significantly less likely to respond to treatment with BoNT-A. CONCLUSION: BoNT-A may be effective in decreasing headache frequency, headache intensity, and headache-related disability in episodic and chronic migraine patients. Duration of illness emerged as a predictor of treatment response. Randomized controlled studies should evaluate headache-related disability as a primary endpoint in patients with episodic and chronic headache.