Effectiveness of topiramate in the prevention of childhood headaches

BACKGROUND: Migraine is a significant problem for many children. Topiramate has been suggested to be effective for the prophylaxis of migraine in adults, but has not yet been examined in children. The drug has been demonstrated to be safe and effective for childhood seizure disorders. The objective of this study was to demonstrate the safety and efficacy of topiramate for the prevention of pediatric migraine. METHODS: Children with frequent migraine were prescribed topiramate for headache prevention. Dosages, serum levels, and Serum Glutamic Oxalacetic Transaminase (SGOT) levels were monitored. Changes in frequency, severity, and duration of headaches were recorded and changes in headache-related disability using PedMIDAS also were measured. RESULTS: Ninety-seven children were treated with topiramate, and 75 were reevaluated 88.7 +/- 35.7 days later, 41 were seen at a second follow-up, and 17 were seen at a third follow-up evaluation. The daily dose reached at second evaluation was 84.0 +/- 38.6 mg/day or 1.42 +/- 0.74 mg/kg/day. This corresponded to a mean serum level of 2.8 +/- 1.6 micro g/mL. The mean headache frequency was reduced from 16.5 +/- 10.0 to 11.6 +/- 10.2 days per month (P<0.001) with a further reduction to 9.4 +/- 8.4 days by the second follow-up (P<0.001). Severity and duration of headache also were reduced. Headache disability improved, with a reduction of Pediatric Migraine Disability Assessment score from 36.0 +/- 42.3 to 20.8 +/- 34.0 at the first follow-up (P<0.05), 19.1 +/- 22.0 at the second follow-up (P<0.005), and 10.9 +/- 16.9 at the third follow-up (P<0.001). Most patients tolerated topiramate well. The most common side effects reported were cognitive (12.5%), weight loss (5.6%), and sensory (2.8%). CONCLUSIONS: Topiramate is potentially an effective prophylactic medication for children with frequent migraine.     

New daily persistent headache in the paediatric population

We conducted a clinic-based study focusing on the clinical features of new-onset chronic daily headaches (CDH) in children and adolescents. The clinical records and headache diaries of 306 children and adolescents were reviewed, to identify 187 with CDH. Relevant information was transferred to a standardized form that included operational criteria for the diagnoses of the headaches. Since we were interested in describing the clinical features of these headaches, we followed the criteria A and B of the 2nd edn of the International Classification of Headache Disorders (ICHD-2) and refer to them as new daily persistent headaches (NDPH) regardless of the presence of migraine features (therefore, this is a modified version of the ICHD-2 criteria). From the 56 adolescents with NDPH, most (91.8%) did not overuse medications. Nearly half (48.1%) reported they could recall the month when their headaches started. NDPH was more common than chronic tension-type headache in both adolescents overusing and not overusing medication. Individuals with NDPH had headaches fulfilling criteria for migraine on an average of 18.5 days per month. On most days, they had migraine-associated symptoms (one of nausea, photophobia or phonophobia)). NDPH is common in children and adolescents with CDH. Most subjects do not overuse medication. Migraine features are common.     

Amitriptyline in the prophylactic treatment of migraine and chronic daily headache

(Headache 2011;51:33‐51) Objective and Background.— Amitriptyline is one of the most commonly used medications in migraine prophylaxis. There have been relatively few placebo‐controlled studies of amitriptyline in migraine prophylaxis or in treatment of chronic daily headache (CDH). This report deals with a large placebo‐controlled trial of amitriptyline vs placebo of 20 weeks duration that included subjects with intermittent migraine (IM) as well as CDH. The study was carried out between 1976 and 1979; however, results have never been fully reported. Methods.— Patients with a history of migraine as defined by the 1962 Ad Hoc Committee report were recruited for this study. Subjects had at least 2 headaches per month, and no limit was placed on the number of headaches per month that could be experienced. The study format included a 4‐week baseline period (Period A) in which all subjects received placebo in a dose of 2 pills per day for one week, 3 pills per day for one week and then 4 pills per day for 2 weeks. Subjects with at least 2 migraine headaches in this period were then entered into Period B and randomized into either amitriptyline or placebo tracks. Medication consisted of identical tablets containing either 25 mg amitriptyline or placebo. Period B was 4 weeks in duration with dose titration identical to Period A. The dose could be reduced if necessary to reduce side effects. The minimum dose was one pill per day. Period C was a 12‐week maintenance or stabilization period in which the patient continued the dose established by week 8 with visits at weeks 12, 16, and 20. Patients kept a headache calendar that was used for data collection. Headache frequency (per month), severity, and duration (hours) were the primary measurement parameters employed for data analysis. Results.— For the entire group, 391 subjects were entered into Period A, 338 were randomized into Period B, 317 (81%) subjects completed the first post‐randomization visit (8 weeks), 255 (65%) completed week 12, 210 (54%) completed week 16, and 186 (48%) completed week 20. Using headache frequency and evaluating parameters of (a) improvement, (b) no change, or (c) worsening relative to baseline, there was a significant improvement in headache frequency for amitriptyline over placebo at 8 weeks (P = .018) but not at 12, 16, or 20 weeks. When amitriptyline and placebo patients were compared for headache frequency at 8, 12, 16, and 20 weeks to their own placebo stabilization period at 4 weeks, statistically significant improvement vs worsening was seen in headache frequency at each evaluation point for both amitriptyline and placebo groups (P ≤ .01) reaching 50% reporting a decrease in frequency in each group and approximately 10% reporting worsening by week 20. There were no significant differences in headache severity or duration between amitriptyline and placebo groups at anytime during the study. Within the study sample, there were 36 amitriptyline and 22 placebo subjects who had headaches ≥17 days/month that fit the current definition of CDH by the Silberstein‐Lipton criteria. These were analyzed separately as a subgroup for comparison of amitriptyline vs placebo using a metric of (1) no change or worsening; (2) up to a 50% improvement; and (3) ≥50% improvement in headache frequency. Amitriptyline was superior to placebo in number with improvement in frequency of ≥50% at 8 weeks (25% vs 5% [P = .031]) and at 16 weeks (46% vs 9% [P = .043]). There was a trend for amitriptyline to be superior to placebo at 12 and 20 weeks but this did not reach significance. Conclusions.— In this study, using headache frequency as the primary metric, for the entire group, amitriptyline was superior to placebo in migraine prophylaxis at 8 weeks but, because of a robust placebo response, not at subsequent time points. For the subgroup with CDH, amitriptyline was statistically significantly superior to placebo at 8 weeks and 16 weeks with a similar but nonsignificant trend at 12 and 20 weeks. Compared with placebo amitriptyline is effective in CDH. Amitriptyline was also significantly effective in IM compared intragroup to its own baseline; however, placebo was equally effective in the same analysis. The reason for the robust placebo response in the IM group is not clear, but has been occasionally reported.     

Prophylactic treatment of pediatric migraine

BACKGROUND: Migraine occurs in 3% to 5% of young children and up to 18% of adolescents. Management requires a tailored regimen of pharmacological and behavioral measures that consider the headache burden and disability. Patients with frequent or disabling attacks (or both) may warrant preventive agents. OBJECTIVE: To investigate the patterns of prophylactic treatment of pediatric migraine within one pediatric neurology practice. METHODS: All charts of patients diagnosed with headache (International Classification of Diseases [ICD] code 784.0) and migraine (codes 346.0, 346.1, and 346.2) during January 2001 July 2001 were retrospectively reviewed to identify diagnosis, demographics, medical decision making, rationale for treatment selections, and outcome assessments. Migraine was diagnosed according to the 1997 proposed pediatric migraine revisions to the International Headache Society. RESULTS: Charts of 250 children and adolescents, aged 3.2 to 18 years (mean, 12), were reviewed. One hundred twenty-six (50%) were prescribed prophylaxis, along with intermittent analgesic agents. Mean age of those provided with daily prophylaxis was 12.4 years (range, 3.9 to 18), and the mean age of those managed with intermittent therapies was 11.5 years. Preventive agents included amitriptyline (n = 73), cyproheptadine (n = 30), propranolol (n = 8), valproic acid (n = 3), naproxen (n = 3), nimodipine (n = 3), imipramine (n = 3), and topiramate (n = 3). Amitriptyline was the most commonly prescribed agent (58%). Ten patients initially treated with other agents were changed to amitriptyline. Fifteen patients required dosing adjustments, 2 stopped treatment, and 7 changed to other agents for lack of efficacy. Mean headache frequency before treatment was 10.9 per month (range, 4 to 15). After treatment, the mean headache frequency decreased to 4.1 per month (range, 0 to 12), a decrease of 62.4% (n = 54). The overall positive response rate was 89%. Cyproheptadine was the second most commonly prescribed agent (mean age, 8.8 years). Thirty patients were initially treated, 5 later changed to cyproheptadine, 6 required dosage changes, 5 changed to other agents for lack of efficacy, and 1 stopped treatment. Mean headache frequency before treatment was 8.4 per month (range, 4 to 15) and following treatment decreased to 3.75 per month (range, 0 to 12), a decrease of 55.3%. The overall positive response rate was 83%. CONCLUSIONS: Fifty percent of patients with migraine were prescribed daily prophylactic medicines, reflecting a referral bias. The most commonly prescribed agents were amitriptyline (preferred for the older patients) and cyproheptadine (preferred for the younger patients). The overall positive response rates were 89% for amitriptyline and 83% for cyproheptadine during a 6-month follow-up. Headache frequencies were reduced with amitriptyline by 62% and with cyproheptadine by 55%. Long-term follow-up of this population is ongoing, and prospective studies are needed.     

Effectiveness of nasal sumatriptan in 5- to 12-year-old children

OBJECTIVE: To assess the tolerability and effectiveness of nasal sumatriptan in the treatment of migraine in 5- to 12-year-old children. BACKGROUND: Although headaches are a common disorder and occur in up to 10.6% of children, many of the new migraine abortive agents have not been well evaluated in this population. It has recently been reported that nasal sumatriptan is effective in the treatment of migraine in adolescents. In younger children, it is yet to be characterized. In addition, many children have significant amounts of vomiting with their migraines, limiting their use of oral medications. DESIGN AND METHODS: Children with headache were evaluated by a child neurologist, child psychologist, and pediatric nurse practitioner. Clinical and International Headache Society diagnoses were established for each child. Patients with headaches that were either unresponsive to oral medications or had significant vomiting were treated with nasal sumatriptan. Initial administration and tolerability were performed in the Headache Center at Cincinnati's Children's Hospital Medical Center. Patients or their parents were contacted to assess the overall effectiveness of nasal sumatriptan after home administration. RESULTS: Ten patients aged between 5 and 12 years (mean, 9.9 years) received either a 5-mg (n = 2) or 20-mg (n = 8) dose of sumatriptan. All 10 patients had a clinical diagnosis of migraine; 7 met the International Headache Society criteria for migraine. The mean age of headache onset was 6.6 years. A total of 57 headaches were treated; 47 (82.5%) responded to sumatriptan. Of the patients who treated headaches, the mean number of headaches treated was 5.2, while the mean number of responsive headaches was 4.3. One patient had no response, 2 patients had a 50% response, and 6 patients had 100% response to the nasal sumatriptan. Three patients reported persistent "bad taste." CONCLUSIONS: This report demonstrates that nasal sumatriptan may be effective in aborting migraine in young children (aged 5 to 12 years). It also suggests that there may be subgroups for which it works well. This information suggests that double-blind, placebo-controlled studies are necessary to determine the overall effectiveness of nasal sumatriptan in this age group.     

Protriptyline, Chronic Tension-Type Headaches, and Weight Loss in Women

Twenty-five women with chronic tension-type headaches were treated with protriptyline for 3 months, with attention paid to days of monthly headaches before and while taking the medication, as well as change in weight and side effects. One patient stopped the medication because of side effects and 2 did not return for follow-up, yielding 22 patients. The typical dose of protriptyline was 20 mg every morning. Eighty-six percent of patients had fewer headaches each month, with the mean dropping from 28.2 to 11.7 days. Seventy-three percent had a 50% or greater reduction in the number of headaches per month. The average weight change was a loss of slightly over 3 pounds during the study period. The advantages and disadvantages of protriptyline in the treatment of chronic tension-type headaches are discussed, as are mechanisms of action.     

Efficacy and safety of levetiracetam in pediatric migraine

BACKGROUND: Headache is a frequent occurrence among children and adolescents. Chronic headaches can be severe and disabling, and require prophylactic treatment; however, additional data on the use of prophylactic medications for migraine in children are needed. OBJECTIVE: To review the efficacy and safety of levetiracetam (Keppra) in pediatric patients with a history of recurrent headache. DESIGN/METHODS: Data from 19 pediatric patients were retrospectively reviewed. The initial dose of levetiracetam was usually 125 or 250 mg twice daily, but varied depending upon clinical judgment. RESULTS: Charts of 9 girls and 10 boys (mean age, 11.9 years) were reviewed. A variety of medications, including triptans, had been used before initiating treatment with levetiracetam. Mean headache frequency before treatment was 6.3 per month (standard deviation [SD], 3.8; confidence interval [CI], 4.4 to 8.1). Duration of headaches ranged from 0.25 to 8 years. Migraine (63.2%) and migraine with aura (15.8%) were the most common types of headache reported. Most patients (89.5%) had headaches that were severe. After treatment, the mean headache frequency decreased to 1.7 per month (SD, 2.7; CI, 0.4 to 3.0), representing a reduction compared with baseline (P <.0001). Levetiracetam eliminated headaches in 10 patients (52.6%), and 7 patients (36.8%) had less severe and less frequent headaches. Levetiracetam did not have an effect on headaches in 2 patients (10.5%). Mean duration of treatment with levetiracetam was 4.1 months. Doses ranged from 125 to 750 mg twice daily. Sixteen patients (84.2%) reported no side effects on levetiracetam. One patient experienced asthenia/somnolence and dizziness, and irritable, hyperactive, and hostile behavior led to discontinuation of levetiracetam in another patient. A third patient experienced irritability and moodiness that attenuated after 1 month of treatment and did not require discontinuation. CONCLUSIONS: In this small retrospective review, levetiracetam was found to be generally well tolerated and appears to be a promising candidate for additional evaluation in well-controlled clinical trials of pediatric patients with 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.     

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

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

Prophylaxis of Migraine and Mixed Headache. A Randomized Controlled Study

SYNOPSIS
The three most commonly used modalities in the prophylactic treatment of headache, namely propranolol, amitriptyline and biofeedback training, were compared individually and in combination. Three hundred forty patients with migraine end 375 patients with mixed headache were randomly allotted to 8 therapeutic categories. The total duration of the study was 312 years and the therapeutic groups were evaluated for a period of 7 months including I month of pretreatment observation. Improvement was assessed by percentage of change in the average headache index during the last three months of evaluation from the pretreatment headache index. In the migraine group 273 patients completed the study. Improvement was significantly higher in patients receiving prophylactic treatment compared to control patients who were on abortive Ergotamine treatment. Propranolol plus biofeedback yielded the best results in the migraine group and addition of amitriptyline did not significantly change the percentage of improvement. Propranolol alone (62%) was significantly superior to amitriptyline (42%) (p < 0.01). The differences between propranolol alone and propranolol plus amitriptyline was not statistically significant.
In the mixed headache group 281 patients completed the study. The most effective treatment was combination of amitriptyline, propranolol and biofeedback training. Amitriptyline alone was superior to propranolol alone in the treatment of mixed headache (p<0.01). A combination of propranolol and amitriptyline was superior to either of those alone. Biofeedback, though by itself, did not appear to be the treatment of choice, significantly contributed to better results as an adjunct when it is combined with pharmacological agents. Concomitant use of propranolol and amitriptyline did not result in any adverse reactions or clinical incompatibility.     

Outcome of a multidisciplinary approach to pediatric migraine at 1, 2, and 5 years

OBJECTIVE: To assess the long-term effectiveness and outcome of multidisciplinary treatment of childhood headaches 1, 2, and 5 years after initial treatment. BACKGROUND: Headaches are a common problem for children and adolescents and for many patients continue into adulthood. Outcome research for pediatric migraine headaches is limited, thus restricting knowledge of the effectiveness of long-term management and outcome. METHODS: Headache characteristics were assessed at the initial visit and were reevaluated 1, 2, and 5 years later in independent sub-groups of consecutive patients. These characteristics included headache frequency, severity, average duration, school absences, and overall perceived response to treatment. RESULTS: At 1 year, 96 patients were evaluated (mean age = 11.0 +/- 3.4, 59% females), 69 patients at 2 years (mean age = 10.6 +/- 3.4, 48% females), and 32 at 5 years (mean age = 10.5 +/- 3.9, 66% females). The headaches were reported as better in 94% at 1 year, 85% at 2 years, and 94% at 5 years. The initial frequency was at 13.4 +/- 10.8 headaches per month, 4.9 +/- 7.0 at 1 year (P < .001), 4.7 +/- 7.6 at 2 years (P < .001), and 4.5 +/- 7.5 at 5 years (P < .001). The severity decreased from 6.8 +/- 1.8 to 5.1 +/- 2.3 at 1 year (P < .001), to 5.0 +/- 2.4 at 2 years (P < .001), and to 4.6 +/- 2.5 at 5 years (P < .01). The school days missed per month showed a marked decrease from 4.5 +/- 9.5 at initial visit to 1.55 +/- 2.8 at 5 years (P < .001). Patients that were only seen at their initial visit and did not choose to return for follow-up had less frequent and shorter duration headaches on initial visit when compared with the rest of the sample and continued to be doing well at the 1-, 2-, and 5-year assessments. CONCLUSIONS: Multidisciplinary treatment was found to be effective for children and adolescents with improvement of multiple outcome variants of pediatric migraine care, including frequency, severity, and school days missed. Patients who did not return to follow-up evaluation were more likely to have less frequent and shorter duration headaches at initial presentation. Regular follow-up care is needed for those children with more severe initial headache presentation.     

Topiramate: a case series study in migraine prophylaxis

We reviewed the electronic records of 74 migraine patients treated with topiramate for more than 6 weeks. Twenty-four patients had episodic migraine and 50 had chronic (transformed) migraine. Most (81%) started treatment at 25 mg per day and reached a dose of 100 mg twice a day (mean dose on the last follow-up visit was 208 mg). The mean headache frequency decreased from 20.6 days to 13.6 days per month (P<0.0001) for all headaches (9.9-5.1 (P<0.0001) and 25.7-17.7 (P<0.001) for episodic migraine and chronic migraine, respectively). The percentage of patients whose headache frequency was reduced by > or =50% was 44.6% for all patients; 58.3 for episodic migraine and 38.0 for chronic migraine. For all patients mean headache severity (10-point scale) was reduced from 6.2 to 4.8 (P<0.0001). Patients on monotherapy (20%) and polytherapy (80%) had similar reductions in headache frequency. Adverse events were usually mild to moderate and were seen in 58.1% (paresthesias in 25%, cognitive difficulties 14.9%). Mean weight loss was 3.1 +/- 4 kg (3.8% of total body weight).     

A novel specific prophylaxis for menstrual-associated migraine

OBJECTIVES: Few migraine prophylactic therapies have demonstrated a 50% reduction in headaches. Even when successful, the economic burden of prophylaxis can discourage widespread usage. This article presents a pilot study of a novel, effective, specific, and inexpensive prophylactic strategy for menstrual-associated migraine. MATERIALS AND METHODS: Eleven women with menstrual-associated migraine and fewer than 14 days of headache per month were identified from prospective enrollment at a gynecology practice and retrospective chart review at a headache center. Exclusion criteria included current use of prophylactic therapy for migraine. METHODS: Patients received open-label therapy with an oral contraceptive containing 20 microg ethinyl estradiol on days 1 to 21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28. Headache intensity and bleeding were recorded in diaries that plotted headache days by oral contraceptive pill days. RESULTS: All of the patients achieved at least a 50% reduction in number of headache days per cycle (mean 77.9% reduction); 10 of the 11 women achieved at least a 50% reduction in weighted headache score (mean 76.3% reduction). CONCLUSIONS: All currently available estrogen-containing oral contraceptives produce a premenstrual fall in ethinyl estradiol concentration equal to or greater than 20 microg. Estrogen supplementation during the placebo week can reduce the magnitude of this fall to less than 20 microg. When the decline is limited to the equivalent of 10 microg ethinyl estradiol, menstrual-associated migraine is prevented. At an average cost of six dollars per headache-day prevented, this represents an effective and inexpensive strategy for a common migraine trigger.     

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.     

Recurrent and chronic headaches in children below 6 years of age

The objective was to determine the frequency of headache subtypes, according to International Headache Society (IHS) criteria, in a population of children below 6 years visiting a Center for Diagnosis and Treatment of Headache in Youth. Medical records of the children below 6 years at their first visit, admitted for headache between 1997 and 2003, were studied. Headache was classified according to the IHS criteria 2004. Children with less than three headache attacks or less than 15 days of daily headache were excluded. We found 1598 medical records of children who visited our Headache Center in the study period. One hundred and five (6.5%) were children younger than 6 years. The mean age at the first medical control was 4.8±1.3 years (range 17–71 months). There were 59 males (56.1%) and 46 females (43.9%). The mean age at onset of headaches was 4.3 years (range 14–69 months). According to the IHS criteria we found 37 cases (35.2%) with migraine, 19 cases (18%) with episodic tension headache, 5 cases (4.8%) with chronic daily headache, 13 cases (12.4%) with primary stabbing headache, 18 cases (17.1%) with post–traumatic headache, 7 cases (6.6%) with other non–dangerous secondary headaches (otorhinolaryngological diseases, post–infectious headaches), 3 cases (2.85%) with dangerous headaches (Arnold–Chiari type 1 malformation, brain tumour) and 9 cases (8.6%) with unclassifiable headaches. Six children (5.7%) reported more than one headache subtype. The prevalence of dangerous headaches was higher than those in school age (χ²=4.70, p<0.05). Our study shows some differences in headaches in this population vs. school children. In fact at this age migraine is the most common headache, but we also found an increase of secondary causes among the chronic/recurrent and daily headaches, especially posttraumatic disorders and potentially dangerous headaches. Finally our study shows the highest prevalence of the idiopathic stabbing headache in pre–school children in comparison with other ages.     

Topiramate versus amitriptyline in migraine prevention: A 26-week,multicenter, randomized,double-blind,double-dummy,parallel-group noninferiority trial in adult migraineurs

Objective: The primary objective of this study was to compare the efficacy and tolerability of topiramate and amitriptyline in the prophylaxis of episodic migraine headache.Methods: This was a 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group noninferiority study. Adults with 3 to 12 migraines per month were randomized in a 1:1 ratio to receive an initial dose of 25 mg/d of either topiramate or amitriptyline, subsequently titrated to a maximum of 100 mg/d (or the maximum tolerated dose). The primary efficacy outcome was the change from prospective baseline in the mean monthly number of migraine episodes. Secondary efficacy variables included changes from the prospective baseline phase to the end of the double-blind phase in the mean monthly (28-day) rate of days with migraine, mean monthly rate of days with headache (migraine and nonmigraine), mean monthly rate of acute abortive medication use, mean monthly migraine duration, and mean monthly migraine severity. Additional secondary efficacy variables included changes in the mean monthly severity of migraine-associated symptoms (photophobia, phonophobia, and nausea), change in the mean monthly frequency f migraine-associated vomiting, and response rates (based on monthly migraine days and total headache days). The Migraine-Specific Quality of Life Questionnaire (MSQ) and the Weight Satisfaction Scale Questionnaire, which measures subjective satisfaction with current weight, were administered. Treatment-emergent adverse events (TEAEs) were monitored through the end of double-blind treatment.Results: The intent-to-treat population included 331 subjects (172 topiramate, 159 amitriptyline; 84.9% female; 84.6% white; mean [SD] age, 38.8 [11.0] years; mean weight, 77.1 [20.1] kg) who provided at least 1 efficacy assessment. The least squares mean (LSM) change from baseline in the mean monthly number of migraine episodes was not significantly different between the topiramate and amitriptyline groups (-2.6 and -2.7, respectively; 95% CI, -0.6 to 0.7). There were no significant differences between treatment groups in any of the prespecified secondary outcome measures. Subjects receiving topiramate had a significantly greater improvement in mean functional disability scores during migraine attacks compared with amitriptyline (LSM change: -0.33 vs -0.19; 95% CI, -0.3 to 0.0; P = 0.040) and in the role function-restrictive, role function-preventive, and emotional function domains of the MSQ (P = 0.012, P = 0.014, and P = 0.029, respectively). Subjects receiving topiramate had a mean weight loss of 2.4 kg, compared with a mean weight gain of 2.4 kg in subjects receiving amitriptyline. Subjects in the topiramate group reported an overall improvement from baseline in weight satisfaction, whereas the amitriptyline group reported an overall deterioration in weight satisfaction (P < 0.001, topiramate vs amitriptyline). TEAEs of mild or moderate severity were reported in 118 subjects (66.7%) in the topiramate group and 112 subjects (66.3%) in the amitriptyline group. Among the most common TEAEs (reported in ±5% of subjects during the double-blind phase) in the topiramate group were paresthesia (29.9%), fatigue (16.9%), somnolence (11.9%), hypoesthesia (10.7%), and nausea (10.2%). The most commonly reported TEAEs in the amitriptyline group were dry mouth (35.5%), fatigue (24.3%), somnolence (17.8%), weight increase (13.6%), dizziness (10.7%), and sinusitis (10.7%).Conclusions: In this noninferiority study, topiramate was at least as effective as amitriptyline in terms of reducing the rate of mean monthly migraine episodes and all prespecified secondary efficacy end points. Topiramate was associated with improvement in some quality-of-life indicators compared with amitriptyline and was associated with weight loss and improved weight satisfaction.     

Transformed migraine is a cause of chronic daily headaches

Chronic daily headaches (CDH) consist of episodes of head pain occurring daily; more than 15 days each month; often associated with a history of migraine, with or without aura; or with a history of tension-type headaches occurring alone or both occurring together. Chronic daily headaches are frequently associated with rebound headaches after ergotamine, barbiturate, caffeine, and analgesic abuse. We previously reported that migraineurs with typical intermittent headaches exhibited excessive cerebral cortical vasodilation after oral acetazolamide which usually precipitated and reproduced their typical headaches. In the present study, cerebral vasodilator responses were tested by measuring changes in local cerebral blood flow (ΔLCBF) utilizing xenon-contrasted CT scanning, before and after oral administration of 14.3 mg/kg of acetazolamide, in 11 patients with CDH. The results were compared with 12 age-matched typical migraineurs, with and without aura, who had a history of migraine attacks occurring at intervals of 1 month or longer. Global and subcortical gray and white matter ΔLCBFs were quantitated and compared between both groups. After acetazolamide, ΔLCBF increased in cortical gray matter by 11.8% among patients with CDH and by 16.7% among migraineurs, with no significant differences between groups. Typical migraine attacks were provoked by acetazolamide in 9 patients (82%) with CDH and in 11 (92%) migraineurs with intermittent headaches. These observations are taken as evidence that at least 82% of patients with CDH have transformed migraine as judged by the provocation by acetazolamide of typical migraine attacks associated with excessive ΔLCBF increases. Serotonin agonists should be considered in the treatment of CDH to avoid ergotamine, caffeine, barbiturate, and analgesic abuse.     

Valproic acid is effective in migraine prophylaxis at low serum levels: a prospective open-label study

OBJECTIVE: We evaluated the efficacy of prophylactic valproic acid treatment (6 months) on the frequency of migraine attacks and the number of migraine headache days with respect to serum levels. BACKGROUND: Valproic acid, a GABAergic drug, has been shown to be effective for migraine prophylaxis. Results from several dose- and serum level-adjusted studies have recommended valproic acid doses within a range of 500 to 1500 mg per day for migraine prophylaxis. Design and METHODS: In this prospective open-label study, 52 patients received valproic acid doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic acid serum levels increased linearly in relation to the valproic acid dose and were between 21 and 107 microg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group 2). RESULTS: The frequency of migraine attacks was significantly reduced in group 1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4 days per month) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with respect to both parameters (P<.05). Side effects were generally mild and temporary. CONCLUSIONS: Due to the lack of additional benefit from higher valproic acid doses (more than 600 mg per day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum level less than 50 microg/mL for the prophylactic treatment of migraine.     

Zonisamide for migraine prophylaxis in refractory patients

Zonisamide is a new antiepileptic drug with multiple mechanisms of action and a favourable pharmacokinetic profile. Preliminary data suggest that zonisamide may be effective in migraine prophylaxis. We evaluated the efficacy and tolerability of zonisamide for migraine prophylaxis in refractory patients. We reviewed the charts of adult patients with International Headache Society-defined episodic migraine (EM) or with transformed migraine (TM) according to the Silberstein-Lipton criteria, who had been treated with zonisamide at our out-patient clinic for at least 60 days. Demographic data, zonisamide dosage and duration of treatment were collected and analysed. Headache frequency, attack duration, headache severity and headache-related disability before and after treatment initiation with zonisamide were compared. Thirty-three patients were included in the study (average age 43.9 +/- 8.4 years; 23 (70%) with TM and 10 (30%) with EM). The patients had failed an average of 6.2 migraine prophylactic drugs prior to zonisamide. The average zonisamide daily dose was 337.9 +/- 146.3 mg and the average duration of treatment was 186.4 +/- 174.0 days. The average number of days with headache per month was reduced in the entire study population from 20.7 +/- 9.5 before zonisamide treatment to 18.0 +/- 11.3 after its initiation (P = 0.06) [in TM from 24.7 +/- 7.3 to 21.0 +/- 10.7 (P = 0.06); in EM from 11.6 +/- 7.6 to 11.0 +/- 9.7 (P = NS)]. No significant changes in other headache parameters were found. Fourteen patients (42.4%) reported adverse events (AEs), the most common of which was fatigue. Most patients (12/14, 85.7%) rated AEs as mild or moderate. In this group of refractory migraine patients, zonisamide therapy did not result in a statistically significant beneficial effect on headache or on associated symptoms.