Showing papers in "Headache in 2002"

What do patients with migraine want from acute migraine treatment

Abstract: Migraine is a common chronic condition with an ever-expanding therapeutic armamentarium. As therapeutic options multiply, it is increasingly important to understand patients' attitudes and preferences regarding various treatment characteristics. Several strategies have evolved to establish treatment priorities in migraine and rationalize and prioritize end points and outcomes to meet the needs of patients. A survey of a population-based sample of migraineurs indicated that an overwhelming majority of patients consider complete relief of head pain, no recurrence, and rapid onset of action as important or very important attributes of acute migraine therapy. An analysis of the relationship between clinical end points and satisfaction found that more than 90% of patients who were pain-free at 2 hours were at least somewhat satisfied with treatment, but satisfaction was dependent on relatively rapid relief. Using a "willingness-to-pay" approach, results indicated that while patients will pay more for migraine treatment that produces rapid, consistent relief without adverse effects or recurrence, speed of complete relief is the most valued attribute. By assessing physician preferences and practices, degree of pain relief and rapid onset were identified as the most important attributes of acute therapy. Based on results from preference studies of triptans, 50% of patients cited more rapid pain relief as the most important determinant of treatment preference. Based on these various approaches, the consensus view is that both clinicians and patients desire a broad range of positive migraine treatment attributes, but rapid onset of complete pain relief is a particularly important priority.

Behavioral and pharmacologic treatment of transformed migraine with analgesic overuse: outcome at 3 years.

Abstract: Objective.—To determine whether combined treatment using medication and biofeedback would be more effective than drug treatment alone for treating transformed migraine complicated by analgesic overuse. Background.—Headaches that are chronic, daily, and aggravated by medication overuse are particularly difficult to treat. Methods.—Sixty-one consecutive patients with transformed migraine and analgesic overuse were treated with inpatient pharmacologic therapy alone or with inpatient pharmacologic therapy combined with biofeedback-assisted relaxation. All patients then were followed prospectively for 3 years. Results.—Both treatment groups exhibited similar levels of improvement immediately following treatment and for 1 year thereafter. At year 3, participants receiving combined treatment showed greater sustained improvement on two of three outcome measures assessed (ie, fewer days of headache and reduced consumption of analgesic medication). In addition, a greater number of patients assigned to pharmacologic treatment alone relapsed (ie, resumed overuse of analgesics) compared to patients receiving combined treatment. Conclusions.—These results suggest that a combination of pharmacologic and behavioral treatment is more effective than drug therapy alone in the long-term management of transformed migraine with analgesic overuse. Confirmation of these findings, as well as extension to other forms of behavioral and cognitive-behavioral treatment, is required.

Children's ibuprofen suspension for the acute treatment of pediatric migraine.

Abstract: Objective.—To compare the efficacy of a single over-the-counter dose (7.5 mg/kg, p.o.) of children's ibuprofen suspension vs. placebo for the acute treatment of pediatric migraine. Background.—Migraine occurs in 4% of young children. There is a paucity of controlled clinical research in the treatment of childhood migraine and there are currently no approved drugs in the USA for treatment of migraine in children 12 years of age. The purpose of this study is to assess the efficacy and tolerability of a single OTC dose of ibuprofen suspension for the acute treatment of childhood migraine. Methods.—Prospective, double-blind, placebo-controlled, parallel group, randomized study of children 6-12 yrs with migraine (I.H.S.-R1997) treating 1 attack with a 7.5 mg/kg liq. ibuprofen vs matching placebo. Efficacy measures: (1) Headache severity based upon a 4 pt scale (severe, mod., mild, no headache) at 30, 60, 90, 120, 180 and 240 minutes post dose, and (2) nausea, vomiting, and photo/phonophobia at 120 min. The 1° endpoint was cumulative % of responders (severe or mod. headache reduced to mild or none) by 120 minutes. Secondary endpoints were headache recurrence within 4-24 hours and need for rescue medicines within 4 hours. Results.—138 enrolled; 84 treated/completed diary. 45 active agent, 39 placebo. The 2 groups were comparable (active: placebo) - Ages: 9: 9.1, gender boy/girl - 1.25: 1.6, and diagnosis: migraine w/o aura - 86%: 79%. Concomitant use of prophylactic Rx: 24%: 10% (Table 3). Table 3. Endpoint Ibuprofen (N=45) Placebo (N=39) P-value Cum. % responders, 2 hr (1° endpoint) 76% 53% 0.006 2 pt. improvement in severity, 2 hr 27 (62%) 11 (28%) 0.004 Median pain score at 2 hr 2 3 <0.02 Headache recurrence (within 4-24 hr) 8 (18%) 14 (36%) 0.06 Need for rescue medication 1 (2%) 15 (38%) <0.001 Nausea was eliminated in 60% of the ibuprofen treated patients and 39% of the placebo group (p<0.001). Vomiting, photophobia and phonophobia had marginal, but not statistically significant, decreases at 2 hours. A striking gender difference was noted (Table 4): Table 4. Endpoint Ibuprofen Placebo P-value Cum. % responders 76% 53% 0.006 BOYS 84% 43.4 <0.0006 GIRLS 65% 66.7 0.8 Headache recurrence 5 13 <0.005 BOYS 0 8 <0.001 GIRLS 5 5 NS No AE's were reported. Conclusion.—Children's ibuprofen suspension at an OTC dose of 7.5 mg/kg is an effective and well-tolerated agent for pain relief in the acute treatment of childhood migraine, particularly in boys. There is a striking difference in gender response rates and placebo responder rates between girls and boys. The boys responded at a statistically significant rate, and girls failed to do so because of a very high placebo responder rate. Multi-center trials are recommended.

The economic impact of migraine: an analysis of direct and indirect costs.

Abstract: OBJECTIVE This study examined whether individuals with migraine incurred greater direct and indirect costs than a matched group free of migraines. METHODS Using population-based survey data, we matched individuals with migraine (n = 1087) and a migraine-free control group one-to-one for age, sex, employment status, and number of comorbidities. We assessed the prior six months' direct medical care in terms of self-reported hospital days and emergency department and physician visits. Costs were computed by multiplying utilization by unit costs and summing across categories. Indirect costs were calculated based on the number of days missed from employment or household activities. RESULTS The sample was 80% female and had an average of 39 years and 0.4 comorbid conditions. Two-thirds were employed. Migraineurs had higher direct medical costs over the prior six months (522 dollars versus 415 dollars, P =.039), primarily due to a greater frequency of physician and emergency department visits. The cost of lost productivity for the migraine group was also higher, by more than 200 dollars (P =.014). The combined total for direct and indirect costs was 1,242 dollars for migraineurs and 929 dollars for the comparison group (P =.006). Additional analyses comparing those with moderate versus severe migraine demonstrated that more severe migraineurs had higher costs for lost productivity (1,021 dollars versus 251 dollars, P<.001) and higher costs when direct and indirect costs were combined (1,656 dollars versus 685 dollars, P<.001). CONCLUSION Migraine is an expensive illness and two-thirds of the financial burden is linked to indirect costs. Consequently, individuals with migraine, employers, and insurance companies all have an economic stake in reducing the migraine burden.

Psychosocial impact of headache and comorbidity with other pains among Swedish school adolescents.

Abstract: Psychosocial Impact of Headache and Comorbidity with Other Pains among Swedish School Adolescents

Chronic daily headache prophylaxis with tizanidine: a double-blind, placebo-controlled, multicenter outcome study.

Abstract: Objective.—To assess the efficacy of tizanidine hydrochloride versus placebo as adjunctive prophylactic therapy for chronic daily headache (chronic migraine, migrainous headache, or tension-type headache). Background.—Tizanidine is an α2-adrenergic agonist that inhibits the release of norepinephrine at both the spinal cord and brain, with antinociceptive effects that are independent of the endogenous opioid system. Previous open-label studies have suggested the drug may be effective for treatment of chronic daily headache. Methods.—Two hundred patients completed a 4-week, single-blind, placebo baseline period, with 134 fulfilling selection criteria and then randomized to tizanidine or placebo. Ninety-two patients completed at least 8 weeks of treatment (tizanidine, n = 45; placebo, n = 47), and 85 patients completed 12 weeks of treatment (tizanidine, n = 44; placebo, n = 41). Most patients (77%) met the diagnostic criteria for migraine of the International Headache Society; 23% had either chronic migrainous headache or chronic tension-type headache. Tizanidine was slowly titrated over 4 weeks to 24 mg or the maximum dose tolerated (mean, 18 mg; SD, 6.4; median, 20.0; range, 2 to 24), divided equally over three dose intervals per day. Overall headache index ([headache days × average intensity × duration in hours]/28 days) was the primary end point. Results.—Tizanidine was shown to be superior to placebo in reducing the overall headache index (P = .0025), as well as mean headache days per week (P = .0193), severe headache days per week (P = .0211), average headache intensity (P = .0108), peak headache intensity (P = .0020), and mean headache duration (P = .0127). The mean percentage improvement during the last 4 weeks of treatment with tizanidine versus placebo was 54% versus 19% for the headache index (P = .0144), 55% versus 21% for severe headache days (P = .0331), 35% versus 19% for headache duration (P = .0142), 35% versus 20% for peak headache intensity (P = .0106), 33% versus 20% for average headache intensity (P = .0281), and 30% versus 22% for total headache days (P = .0593). Patients receiving tizanidine also scored higher ratings of overall headache improvement on a visual analog scale (P = .0069). There was no statistically significant difference in outcome for patients with chronic migraine versus those with only migrainous or tension-type headache. Adverse effects reported by more than 10% of the patients included somnolence (47%), dizziness (24%), dry mouth (23%), and asthenia (19%). Dropouts due to adverse events did not differ significantly between tizanidine and placebo. Conclusions.—The results support tizanidine as an effective prophylactic adjunct for chronic daily headache, including migraine, migrainous headache, and tension-type headache. These results also suggest the possible importance of an α2-adrenergic mechanism underlying the pathophysiology of this spectrum of headache disorders.

Chronic daily headache: identification of factors associated with induction and transformation.

Abstract: Background.—Chronic daily headache (CDH) is one of the more frequently encountered headache syndromes at major tertiary care centers. The analysis of factors related to the transformation from episodic to chronic migraine (CM) and to the de novo development of new daily persistent headache (NDPH) remain poorly understood. Objectives.—To identify somatic factors and lifestyle factors associated with the development of CM and NDPH. Methods.—We used a randomized case-control design to study the following groups: 1) CM with analgesic overuse (ARH), n = 399; 2) CM without analgesic overuse, n = 158; and 3) NDPH, n = 69. These groups were compared with two control groups: 1) episodic migraine, n = 100; and 2) chronic posttraumatic headache (CPTH); n = 65. Associated medical conditions were assessed. We investigated the case groups for any association with somatic or behavioral factors. Data were analyzed by the two-sided Fischer's exact test, with the odds ratio being calculated considering a 95% confidence interval using the approximation of Woolf. Results.—When the active groups were compared with the episodic migraine group, the following associations were found: 1) ARH: hypertension and daily consumption of caffeine; 2) CM: allergies, asthma, hypothyroidism, hypertension, and daily consumption of caffeine; and 3) NDPH: allergies, asthma, hypothyroidism, and consumption of alcohol more than three times per week. The following associations were found when comparing the active groups with CPTH: 1) ARH: asthma and hypertension; 2) CM: allergies, asthma, hypothyroidism, hypertension, and daily consumption of caffeine; and 3) NDPH: allergies, asthma, hypothyroidism, and consumption of alcohol more than three times per week. Conclusions.—Several strong correlations were obtained between patients with specific types of CDH and certain somatic conditions or behaviors; some have not been previously described. Transformation of previously episodic headache or development of a NDPH thus may be related to certain medical conditions and behaviors beyond the frequently incriminated precipitant analgesic overuse. As similar results were obtained when CPTH was used as a control, the correlation is more complex than simple comorbidity.

Effectiveness of multidisciplinary intervention in the treatment of migraine: a randomized clinical trial.

Abstract: Objective.—To test the effectiveness of a multidisciplinary management program for migraine treatment in a group, low cost, nonclinical setting. Design.—A prospective, randomized, clinical trial. Background.—Although numerous studies document the efficacy of pharmacological migraine management, it is unclear whether an effective long-term management approach exists. Methods.—Eighty men and women were randomly assigned to 1 of 2 groups. The intervention group consisted of a neurologist and physical therapist intake and discharge, 18 group-supervised exercise therapy sessions, 2 group stress management and relaxation therapy lectures, 1 group dietary lecture, and 2 massage therapy sessions. The control group consisted of standard care with the patient's family physician. Outcome measures included self-perceived pain intensity, frequency, and duration; functional status; quality of life; health status; depression; prescription and nonprescription medication use; and work status. Outcomes were measured at the end of the 6-week intervention and at a 3-month follow-up. Results.—Forty-one of 44 patients from the intervention group and all 36 patients from the control group completed the study. There were no statistically significant differences between the 2 groups before intervention. Intention to treat analysis revealed that the intervention group experienced statistically significant changes in self-perceived pain frequency (P = .000), pain intensity (P = .001), pain duration (P = .000), functional status (P = .000), quality of life (P = .000), health status (P = .000), pain related disability (P = .000), and depression (P = .000); these differences retained their significance at the 3-month follow-up. There were no statistically significant changes in medication use or work status. Conclusions.—Positive health related outcomes in migraine can be obtained with a low cost, group, multidisciplinary intervention in a community based nonclinical setting.

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a randomized, double-blind, placebo-controlled study.

Abstract: Objective.—To investigate the tolerability and efficacy of rizatriptan 5 mg in adolescent migraineurs. Methods.—Randomized, double-blind, placebo-controlled study. Patients aged 12 to 17 years received rizatriptan 5 mg (n=149) or placebo (n=147) for a moderate or severe headache and for up to two recurrences. Headache severity, presence or absence of associated symptoms, and functional disability were assessed over a 4-hour postdose period, and any adverse events were recorded. The primary efficacy measure was pain-free status at 2 hours postdose. Results.—Rizatriptan 5 mg was well tolerated. The most commonly reported adverse events (all with incidence of 5% or less) among patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue, nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32% for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients with pain relief (reduction of predose pain intensity to mild or none) at 2 hours was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates were higher than those typically observed in previous studies of rizatriptan in adults. Compared with placebo, rizatriptan significantly improved functional disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis showed a significant benefit of rizatriptan versus placebo in the percentage of patients who had pain relief when their migraine attacks were treated on weekends (65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the weekend placebo response rate was similar to that seen in adults. Conclusions.—Rizatriptan 5 mg was well tolerated and effective on some measures when used in adolescents for the treatment of a migraine attack.

Migraine and psychiatric comorbidity: from theory and hypotheses to clinical application.

Abstract: Objective.—To review psychiatric issues that accompany migraine and means of addressing these issues. Background.—Psychiatric factors and migraine may interact in three general ways, etiologically, psychophysiologically or biobehaviorally, and comorbidly (the two disorders coexist), which is the present focus. There are several possible mechanisms of comorbidity. The relation between two disorders may be a result of chance. One disorder can cause another disorder: Diabetes can cause diabetic neuropathy. There might be shared environmental risks: Head trauma can cause both posttraumatic epilepsy and posttraumatic headache. And there may be environmental or genetic risk factors that produce a brain state giving rise to both conditions, that is, there may be some common biology underlying both conditions. This last mechanism seems to be the most likely one underlying comorbidity of migraine and psychiatric disorders. We introduce a possible role for classical paradigms of learned helplessness in regard to psychiatric comorbid depressive and anxiety disorders and migraine. Results.—There appears to be an association between migraine and affective disorders, particularly depression and anxiety. There are a number of formal tools for recognizing depression, but clinical evaluation should not be overlooked. Once diagnosed, depression and anxiety should be treated, both to improve the success of migraine treatment and to improve the patient's quality of life. Patients with recurring headaches are much more likely to overuse and misuse, rather than abuse, pain medications. It is important to be alert for signs that the patient may be misusing medication. Behavioral approaches can surround and support pharmacological therapy. Conclusions.—Migraine is often comorbid with psychiatric disorders, particularly depression and anxiety. The relationship is likely based on shared mechanisms and successful treatment is possible.

Acupuncture in the prophylactic treatment of migraine without aura: a comparison with flunarizine.

Abstract: Objectives.—In a randomized controlled trial extending over 6 months, we evaluated the effectiveness of acupuncture versus flunarizine in the prophylactic treatment of migraine without aura. Methods.—One hundred sixty women with migraines were randomly assigned to acupuncture treatment (group A, n � 80) or to an oral therapy with flunarizine (group F, n � 80). In group A, acupuncture was carried out in weekly sessions for the first 2 months and then once a month for the next 4 months. The same acupoints were used at each treatment: LR3 Taichong , SP6 Sanyinjiao , ST36 Zusanli , CV12 Zhongwan , LI4 Hegu , PC6 Neiguan , GB20 Fengchi , GB14 Yangbai , EX-HN5 Taiyang , GV20 Baihui. In group F, 10 mg flunarizine were given daily for the first 2 months and then for 20 days per month for the next 4 months. Results.—The frequency of attacks and use of symptomatic drugs significantly decreased during treatment in both groups. The number of attacks after 2 and 4 months of therapy was significantly lower in group A than in group F, and analgesic consumption was significantly lower in group A at 2 months of treatment. At 6 months no such differences existed between the two treatment groups. Pain intensity was significantly reduced only by acupuncture treatment. Side effects were significantly less frequent in group A. Conclusions.—Acupuncture proved to be adequate for migraine prophylaxis. Relative to flunarizine, acupuncture treatment exhibited greater effectiveness in the first months of therapy and superior tolerability.

Effectiveness of topiramate in the prevention of childhood headaches.

Abstract: 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.

Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey.

Abstract: Objective.—To investigate the co-occurrence of migraine without aura (MWOA) and migraine with aura (MWA) in a population-based twin survey. Background.—Migraine without aura and MWA are multifactorial disorders. If MWOA and MWA share common genes, co-occurrence should be observed more frequently than expected, ie, the product of the prevalence in the general population. Material and Methods.—The study population included all living Danish monozygotic (MZ) and same-gender dizygotic (DZ) twin pairs born between 1953 and 1960: 5360 twins (2026 MZ, 3334 DZ). The sample included 2840 men and 2520 women. All received a posted questionnaire, and those with possible migraine were interviewed via telephone by trained physicians (V.U. or M.G.). Twins who did not respond to the questionnaire and who had a co-twin with possible migraine were contacted by telephone. The questionnaire response rate was 87% (4660 of 5360), and the telephone interview was participated in by 90% (2035 of 2272). The physician interviewers were unaware of questionnaire answers, zygosity, and the clinical diagnosis of the co-twin. The criteria of the International Headache Society were used to establish a diagnosis of migraine. Results.—Lifetime prevalence in the twin sample: 7% of men and 19% of women had MWOA, while 7% of men and 8% of women had MWA. Lifetime prevalence of MWA in twin pairs with MWOA: MZ men, 2% (1 of 47); MZ women, 6% (5 of 90); DZ men, 9% (7 of 75); and DZ women, 10% (19 of 182). Lifetime prevalence of MWOA in twin pairs with MWA: MZ men, 3% (1 of 33); MZ women, 5% (3 of 58); DZ men, 9% (4 of 44); and DZ women, 13% (10 of 76). The observed and the expected numbers of twins with co-occurrence of MWOA and MWA based on the prevalence in the general population were not significantly different in either men or women (men, P=.1 and women, P=.5). Conclusion.—The results strongly suggest that MWOA and MWA are distinct disorders, and identification of common genes for MWOA and MWA, thus, should not be expected to result from future genetic research.

Within‐Patient Early Versus Delayed Treatment of Migraine Attacks With Almotriptan: The Sooner the Better

Abstract: Background.—Migraine sufferers typically have been instructed to delay triptan therapy until headache intensity is at least moderate. Recent data suggest that earlier use of triptans may be more beneficial. Objective.—To address the potential “within-patient” benefit of intervention with almotriptan 12.5 mg for migraine headache of mild intensity. Methods.—We performed a post hoc analysis of a subgroup of patients from a large, open-label, long-term clinical trial wherein 762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity. Specifically, we evaluated the efficacy and safety of treatment in those patients who had treated at least 3 “mild” attacks and 3 “moderate/severe” attacks, examining rates of pain-free status, use of rescue medication, early recurrence, and adverse events for the first 3 mild and the first 3 moderate/severe attacks treated. Results.—There were 118 migraineurs and 708 attacks available for analysis. At 1 hour following treatment, pain-free status was achieved in 47% of mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2 hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue medication was required in 8% of mild attacks and in 13% of moderate/severe attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and 33% for moderate/severe attacks (P<.01). There was no difference in the incidence of adverse events for mild versus moderate/severe attacks (6% versus 7%). Conclusion.—These results support early intervention with oral triptan therapy. When used for mild intensity head pain, almotriptan 12.5 mg produced a significantly higher incidence of pain-free status at 1 and 2 hours and lower incidences of early headache recurrence or need for rescue medication.

Primary headaches: a convergence hypothesis.

Abstract: After reviewing the historic differentiation between migraine and tension-type headache, the authors note that the similarities between these two types of primary headaches outweigh the differences, and so hypothesize that these headaches share a common pathophysiology. The convergence hypothesis for primary headaches links the clinical features of an evolving headache to current pathophysiological models. The authors suggest that successive symptoms experienced clinically reflect an escalating pathophysiological process, beginning with the premonitory period and progressing into tension-type headache and, if uninterrupted, finally into migraine. The clinical manifestations of other headache types, such as so-called sinus headache or temporomandibular headache, may also be explained by this model. A convergence hypothesis for primary headaches has important implications for earlier recognition, diagnosis, and treatment.

Sodium Valproate Prophylaxis in Childhood Migraine

Abstract: Migraine is a cause of recurrent headache in childhood. The efficacy of sodium valproate is well known in the prophylactic treatment of adult migraine, but there are few studies involving the drug's effect in pediatric migraine. Objective.—To determine the efficacy of sodium valproate in the prophylactic treatment of childhood migraine. Methods.—Fifteen children with migraine according to International Headache Society criteria were included in the study. Headache severity was measured and assessed by Algology unit by a using visual analog scale and a numerical rating scale. All of the subjects were asked to keep a headache diary for 8 weeks. Three subjects who had no headache attacks during the baseline period and two cases who were lost to follow up were excluded. Thus, sodium valproate was initiated in 10 subjects (six boys, four girls), 500 mg/night, and the daily dose was increased up to 1000 mg according to blood levels. Their ages ranged from 9 to 17 (mean age 13.6 ± 3.2 years). Therapy continued for at least 12 weeks. Results.—Headache severity as measured via the mean visual analog score was 6.8 ± 1.8 at baseline and was 0.7 ± 1.2 at the end of the treatment period (P = 0.000). Mean headache attacks per month were 6 ± 4.2 at baseline and were 0.8 ± 1.9 at the end of the treatment period (P = 0.002). The duration of headache was significantly decreased from a mean of 5.5 ± 3.9 hours to 1.1 ± 2.5 hours with treatment (P = 0.001). The observed side effects were dizziness, drowsiness, and increase in appetite; none required drug withdrawal. In two cases, headache attacks recurred after the cessation of valproate, and therapy was restarted. Headache control lasted for six months following cessation of the drug in the remainder of the subjects. Conclusion.—Sodium valproate appears to be effective and safe in selected patients with childhood migraine.

Prophylaxis of migraine, transformed migraine, and cluster headache with topiramate.

Abstract: Objective.—To assess the efficacy and tolerability of topiramate for prophylaxis of migraine and cluster headache via a retrospective chart analysis. Background.—Topiramate has multiple mechanisms of action that could potentially contribute to migraine prophylaxis. We conducted a retrospective chart review to assess the efficacy of topiramate as add-on therapy in patients with transformed migraine or cluster headache, and as first-line therapy in patients with episodic migraine. Methods.—Patients diagnosed with transformed migraine, episodic migraine, or cluster headache, who received topiramate either as add-on therapy or monotherapy were selected via retrospective chart review. Patients had begun topiramate therapy at 25 mg/day for the first week and increased their dosage by 25 mg/week to a maximum of 200 mg/day. Topiramate was used as add-on therapy for patients with transformed migraine and cluster headache, and as a first-line monotherapy in patients with episodic migraine who had no previous prophylactic therapy. The outcome parameters examined included a mean 28-day migraine frequency, migraine severity, number of headache days/month, number of abortive medication tablets/month, patient global evaluation, and the MIDAS scale. Results.—One hundred seventy-eight patients (transformed migraine: n = 96; episodic migraine: n = 70; and cluster headache: n = 12) were included in the retrospective analysis. The mean dose of topiramate for all patients was 87.5 mg/day. For patients with transformed migraine, mean migraine frequency decreased from 6.3/28 days to 3.7 (P = 0.005). Mean severity decreased from 7.1 to 3.8 on a 10-point scale, with 10 representing the most severe pain (P = 0.003). The mean number of headache days/month decreased from 22.1 to 9.6 (P = 0.001), and the mean number of abortive medication tablets decreased from 28.7/month to 10.6 (P = 0.001). Patient global evaluation indicated substantial or moderate improvement in 53% of patients with transformed migraine who used topiramate as add-on therapy. Mean MIDAS scale values decreased from 90.2 to 24.9 (P< 0.0001). The 70 episodic migraine patients who were administered topiramate as first-line therapy exhibited a decrease in mean migraine frequency (5.8/28 days to 1.9, P = 0.001), while mean migraine severity decreased from 8.1 to 2.0 (P = 0.003). Sixty-one percent of patients reported marked improvement. Nine of the 12 cluster headache patients exhibited substantial or moderate improvement in symptoms, whereas three had no improvement. The most common adverse effects were paresthesias (12%), cognitive effects (11%), and dizziness (6%). Eight patients discontinued topiramate due to adverse effects; cognitive effects were the most common reason. No patient discontinued topiramate treatment due to lack of efficacy. Twelve percent of patients lost more than 5 lbs during treatment (a range of 5-120 lbs). Conclusion.—For both patients with transformed migraine (add-on therapy) and patients with episodic migraine (first-line monotherapy), topiramate yielded significant reductions in migraine frequency, migraine severity, number of headache days/month, and use of abortive medications. Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache. Prospective double-blind, placebo-controlled trials will be required to confirm our results.

Tolerability and Safety of Frovatriptan With Short‐ and Long‐term Use for Treatment of Migraine and in Comparison With Sumatriptan

Abstract: Objective.—To evaluate the tolerability and safety of frovatriptan 2.5 mg in patients with migraine. Background.—Frovatriptan is a new, selective serotonin agonist (triptan) developed for the acute treatment of migraine. Dose range-finding studies identified 2.5 mg as the dose that conferred the optimal combination of efficacy and tolerability. Methods.—The tolerability and safety of frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100 mg, as well as a 12-month open-label study during which patients could take up to three doses of frovatriptan 2.5 mg within a 24-hour period. Safety and tolerability were assessed through the collection of adverse events, monitoring of heart rate and blood pressure performance of 12-lead electrocardiogram, hematology screen, and blood chemistry studies. Results.—In the short-term studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the 12-month study, 496 patients treated 13 878 migraine attacks. Frovatriptan was well tolerated in the short- and long-term studies with 1% of patients in the short-term studies and 5% of patients in the long-term study withdrawing due to lack of tolerability. The incidence of adverse events was higher in the frovatriptan-treated patients than in the patients who took placebo (47% versus 34%) and the spectrum of adverse events was similar. When compared to sumatriptan 100 mg, significantly fewer patients taking frovatriptan experienced adverse events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62 versus 0.91), there were also fewer adverse events suggestive of cardiovascular symptoms in the frovatriptan group. Analysis of the entire clinical database (n=2392) demonstrated that frovatriptan was well tolerated by the patients regardless of their age, gender, race, concomitant medication, or the presence of cardiovascular risk factors. No effects of frovatriptan on heart rate, blood pressure, 12-lead electrocardiogram, hematology screen, or blood chemistry were observed. No patient suffered any treatment-related serious adverse event. Conclusions.—Short- and long-term use of frovatriptan 2.5 mg was well tolerated by a wide variety of patients. Frovatriptan treatment produced an adverse events profile similar to that of placebo, and in a direct comparison study was better tolerated than sumatriptan 100 mg.

Headache Associated with Epileptic Seizures: Epidemiology and Clinical Characteristics

Abstract: Objective.—To investigate the incidence and characteristics of seizure-associated headaches and the modalities of treatment. Background.—Systematic investigations of the characteristics of seizure-associated headaches are rare. Although data in the literature on the incidence of postictal headaches range between 37% and 51%, experiences with their treatment are limited and pathophysiological concepts do not exist. Methods.—One hundred ten epileptic outpatients from an epilepsy referral center participated in a semi-standardized interview about headaches associated with epileptic seizures. The characteristics of these patients and of 15 additionally recruited patients with known postictal headaches were analyzed. Results.—The incidence of seizure-associated headaches was 43% (n = 47). Forty-three patients had exclusively postictal headaches. One patient had exclusively preictal headaches. Three patients had both pre- and postictal headaches. The duration of postictal headaches was longer than 4 hours in 62.5% of the patients. In the majority of patients, postictal headaches occurred in more than 50% of the seizures. Postictal headaches were treated by self-medication in 19 patients (30%). No patient treated headaches according to a medical prescription. In 11 patients, postictal migraine was untreated. Postictal headaches were associated with focal seizures in 23 patients and/or with generalized seizures in 54 patients. According to the headache classification of the International Headache Society, headaches were classified as migraine-type in 34% of patients and as tension-type headache in 34% of patients. Headaches could not be classified in 21% of patients. Patients with and without postictal headaches did not differ as to localization of the epileptogenic zone or to the number of prescribed antiepileptic drugs. There was no relationship between the localization of the epileptogenic focus, localization of the headache, or the headache classification. Conclusions.—Headaches associated with partial and generalized seizures are frequent and undertreated. Treatment should consider both the headache syndrome and the general guidelines for treating primary headaches. The pathophysiology of seizure-associated headaches cannot be explained by the epileptic syndrome.

Refining the Clinical Spectrum of Chronic Paroxysmal Hemicrania: A Review of 74 Patients

Abstract: Objective To refine the clinical spectrum of chronic paroxysmal hemicrania (CPH). Methods From 1976 to 1996, 74 patients were diagnosed with CPH by Mayo Clinic neurologists. Data were collected on those cases. Results Of the 74 patients, 62% were women. Most (93%; 69/74) had strictly unilateral pain, 78% (53/68) had daily attacks, and 4% (2/47) had no autonomic features. The mean usual attack duration was 26 minutes, whereas the mean usual attack frequency was six per day. Three-quarters (30/40) had a consistent response to indomethacin, whereas 25% did not. In 34 patients, there were incomplete data concerning indomethacin response. Some (9/13) were able to stop indomethacin without headache recurrence. Few (2/25) stopped indomethacin because of side effects. Two patients had initial responses to indomethacin that did not persist. Oxygen was beneficial in three patients. Three surgically treatable cases of secondary CPH were identified. Conclusions Attack duration is the clinical feature that best distinguishes CPH from other trigeminal autonomic cephalgias. Although long-term therapy with indomethacin is generally well-tolerated, some patients who clinically appear to have CPH do not respond to indomethacin, and tachyphylaxis may develop in some cases. Some patients are able to stop indomethacin without headache recurrence, highlighting the importance of a trial of discontinuation. A consistent clinical profile and treatment response do not exclude the possibility of intracranial pathology.

Melatonin as Adjunctive Therapy in the Prophylaxis of Cluster Headache: A Pilot Study

Abstract: 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.

Prevalence of Menstrually Related Migraine and Nonmigraine Primary Headache in Female Students of Belgrade University

Abstract: Objectives.—To determine prevalence and characteristics of menstrually related migraine and nonmigraine headache in female students of Belgrade University. Method.—A questionnaire was administered to female students during randomly selected classes of the Schools of Medicine and Pharmacy. Diagnoses were assigned according to the criteria of the International Headache Society and MacGregor's stricter definition of “menstrual” migraine. Results.—Of 1943 female students (18 to 28 years old), 1298 (66.8%) had primary headaches. Among 1298 students with headache, 245 (12.6%) had migraine and 1053 (54.2%) had nonmigraine headache. The prevalence rates of migraine versus nonmigraine headache in relation to the menstrual cycle were: premenstrual, 0.9% versus 4.4%; menstrual, 1.5% versus 1.5%; menstrually associated, 6.1% versus 10.1%; menstrually unchanged, 2.7% versus 19.2%; and menstrually unrelated, 1.4% versus 18.9%. Female students with migraine had menstrually related attacks more frequently than students with nonmigraine headache (67.7% versus 29.5%). This difference was most prominent among students with menstrual migraine compared with students with menstrual nonmigraine headache (12.2% versus 2.7%). Exacerbation of migraine during menstruation was slightly more severe and more complex than exacerbation of nonmigraine headache. Female students with migraine versus nonmigraine headache did not differ significantly in age, age at onset of menarche, or age at onset of headache. Female students with migraine were significantly more likely to report a positive family history for migraine and menstrual migraine, severe attacks, reduced work activity, and aura. Conclusion.—The results obtained are in accord with the prevailing opinion that there is a relationship between migraine and female sex hormones, and suggest that women with nonmigraine headache are also susceptible to hormonal fluctuations.

Chronic daily headache in children and adolescents presenting to tertiary headache clinics.

Abstract: Background.—Adults with chronic daily headache often describe a transformation from episodic migraine and partial retention of migrainous features. Although chronic daily headache has not been investigated as carefully in the pediatric population, one study showed a predominance of coexisting daily headache and episodic migraine, without a clear history of transformation. Objective.—To identify the clinical features of chronic daily headache in children and adolescents, to evaluate the efficacy of current headache classification criteria, and to compare the features of coexistent daily and episodic headaches so as to determine whether they represent separate syndromes or different stages in the “transformation” process. Design.—We surveyed 189 consecutive patients, 18 years of age or younger, who presented for initial evaluation of daily or near daily headache at one of 9 tertiary headache clinics. Data were collected in semistructured interviews employing a standard questionnaire and analyzed using Statistical Analysis Systems and Stata statistical software computer programs. Results.—Of the patients enrolled, 70% were female and 87% were white. Mean age was 13.0 ± 3.1 years. Male gender was associated with a higher degree of reported disability. A family history of headache (typically migraine) was described in 79%. Use of nonsteroidal anti-inflammatory drugs 5 days per week or more was reported by 44% of patients. The International Headache Society (IHS) criteria failed to classify 64% of patients and criteria proposed by Silberstein et al failed to classify 31% of patients. Participating physicians misclassified patients according to criteria of the IHS and Silberstein et al in one third of cases. Nearly one quarter of patients reported two separate headache types with distinguishing characteristics. “Baseline” headache was present 27.3 ± 4.1 days per month with a mean pain intensity of 5.9 ± 2.1 on a 10-point scale. Superimposed episodic headache occurred 4.7 ± 3.8 days per month with a mean pain intensity of 8.4 ± 1.4, and was more often accompanied by other migrainous symptoms. After logistic regression to control for pain intensity, the only statistically significant difference between the two headache types was a lower prevalence of tension-type head pain with the superimposed headache. Conclusions.—Our data suggest that rather than having two coexistent headache types, children and adolescents with chronic daily headache have a single syndrome that, in many cases, will paroxysmally worsen and gather migrainous features.

Migraine and coronary heart disease in women and men

Abstract: Objective.—We evaluated migraine as an independent risk factor for subsequent coronary heart disease (CHD) events among women in the Women’s Health Study (WHS) and men in the Physicians’ Health Study (PHS). Background.—Although several studies have suggested that migraine is associated with increased risk of stroke, there are few and conflicting data on whether migraine predicts risk of future CHD events. Methods.—The WHS is an ongoing randomized, double-blind, placebo-controlled trial of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer in 39,876 women health professionals aged � 45 years in 1993, and the PHS is a completed randomized, double-blind, placebo-controlled trial of aspirin and � -carotene in the primary prevention of cardiovascular disease and cancer in 22,071 men physicians aged 40 to 84 years in 1982. Primary endpoints were defined as major CHD (nonfatal myocardial infarction [MI] or fatal CHD) and total CHD (major CHD plus angina and coronary revascularization). Results.—After adjusting for other CHD risk factors, female health professionals and male physicians reporting migraine were not at increased risk for subsequent major CHD (women: relative risk [RR], 0.83; 95% confidence interval [CI], 0.53 to 1.29; men: RR, 1.02; 95% Cl, 0.79 to 1.31) or total CHD (women: RR, 1.01; 95% Cl, 0.76 to 1.34; men: RR, 0.98; 95% Cl, 0.82 to 1.18). When considered separately, there was also no increase in risk of MI or angina. Conclusion.—These prospective data suggest that migraine is not associated with increased risk of subsequent CHD events in women or men.

Depression, automatic thoughts, alexithymia, and assertiveness in patients with tension-type headache.

Abstract: Objective.—The role of psychological factors related to headache has long been a focus of investigation. The aim of this study was to evaluate depression, automatic thoughts, alexithymia, and assertiveness in persons with tension-type headache and to compare the results with those from healthy controls. Methods.—One hundred five subjects with tension-type headache (according to the criteria of the International Headache Society classification) and 70 controls were studied. The Beck Depression Inventory, Automatic Thoughts Scale, Toronto Alexithymia Scale, and Rathus Assertiveness Schedule were administered to both groups. Sociodemographic variables and headache features were evaluated via a semistructured scale. Results.—Compared with healthy controls, the subjects with headache had significantly higher scores on measures of depression, automatic thoughts, and alexithymia and lower scores on assertiveness. Subjects with chronic tension-type headache had higher depression and automatic thoughts scores than those with episodic tension-type headache. Conclusions.—These findings suggested that persons with tension-type headache have high depression scores and also may have difficulty with expression of their emotions. Headache frequency appears to influence the likelihood of coexisting depression.

Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with menstrual migraine.

Abstract: Objective It has been suggested that magnesium deficiency may play an important role in menstrual migraine and that the serum ionized calcium (ICa2+)/ionized magnesium (IMg2+) ratio is important in migraine headache. Studies were designed to test these hypotheses. Design We prospectively evaluated 270 women seen at a headache clinic and in 61 women with menstrual migraine measured IMg2+, total magnesium, and ICa2+ levels so as to calculate the ICa2+/IMg2+ ratio. Results The incidences of IMg2+ deficiency were 45% during menstrual attacks, 15% during nonmenstrual attacks, 14% during menstruation without a migraine, and 15% between menstruations and between migraine attacks. The serum ICa2+ levels were within our reference range, but the ICa2+/IMg2+ ratio was elevated (P Conclusions The high incidence of IMg2+ deficiency and the elevated ICa2+/IMg2+ ratio during menstrual migraine confirm previous suggestions of a possible role for magnesium deficiency in the development of menstrual migraine.

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

Abstract: 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 × 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 .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.

Olanzapine in the Treatment of Refractory Migraine and Chronic Daily Headache

Abstract: Background.—Olanzapine, a thienobenzodiazepine, is a new “atypical” antipsychotic drug. Olanzapine's pharmacologic properties suggest it would be effective for headaches, and its propensity for inducing acute extrapyramidal reactions or tardive dyskinesia is relatively low. We thus decided to assess the value of olanzapine in the treatment of chronic refractory headache. Methods.—We reviewed the records of 50 patients with refractory headache who were treated with olanzapine for at least 3 months. All previously had failed treatment with at least four preventative medications. The daily dose of olanzapine varied from 2.5 to 35 mg; most patients (n = 19) received 5 mg or 10 mg (n = 17) a day. Results.—Treatment resulted in a statistically significant decrease in headache days relative to baseline, from 27.5 ± 4.9 before treatment to 21.1±10.7 after treatment (P < .001, Student t test). The difference in headache severity (0 to 10 scale) before treatment (8.7±1.6) and after treatment (2.2 ± 2.1) was also statistically significant (P < .001). Conclusion.—Olanzapine may be effective for patients with refractory headache, including those who have failed a number of other prophylactic agents. Olanzapine should receive particular consideration for patients with refractory headache who have mania, bipolar disorder, or psychotic depression or whose headaches previously responded to other neuroleptic medications.

Quality of life, coping strategies, and family routines in children with headache.

Abstract: Objective.—To identify the relationship between headache severity, child coping, and quality of life (QoL) in the context of everyday family life. Background.—In the pediatric headache research only 3 studies have examined children's coping strategies and only 4 studies considered QoL. Methods.—A sample of 48 Italian families with children seeking treatment for primary headaches was interviewed using an adaptation of the Ecocultural Family Interview (EFI). The EFI is a parent interview that explores the daily routines of family life in which the child and parent participate and the main concerns regarding how that routine is organized. Results.—As expected the Lisrel analyses consistently showed that QoL is affected by a child's coping abilities in a causal direction. Headache frequency and duration have a significant impact on a child's QoL. The family daily routine influences significantly both the child's coping ability and QoL. Surprisingly enough, children's coping strategies are not related to headache severity. Conclusions.—More research is needed on the causal factors influencing child's ability to cope with pain, and in particular more attention should be devoted to the contextual and family factors related to pediatric headache.