MEDLINE Abstracts: Headache Prophylaxis
What's new concerning the prophylaxis of migraine and other headaches? Find out in this easy-to-navigate compilation of MEDLINE and conference abstracts compiled by the editors at Medscape.
Saper JR, Lake AE, Tepper SJ
Headache. 2001;41:465-474
Objective: To assess effectiveness, tolerability, and safety of nefazodone as a prophylactic agent for chronic daily headache.
Background: Nefazodone is a potent, selective 5-HT2 antagonist with a distinct and atypical mechanism of action. The evolution of intermittent migraine to chronic daily headache has been linked to upregulation of 5-HT2 receptors as well as other factors. Other effective migraine prophylactic medications are also 5-HT2 antagonists. Although research has shown nefazodone to be an effective antidepressant with a good tolerability and safety profile, its potential role in headache prophylaxis has not been tested.
Design: This was a 2-center open-label study with a 4-week baseline, followed by 12 weeks of treatment with nefazodone at a median dose of 300 mg (mean, 303.66 +/- 65.57 mg; range, 100 to 450 mg, depending on tolerability). Potential patients were required to report more than 15 days of headache per month for at least 3 months prior to screening. Only patients with at least 15 days of recorded headache during baseline were included in the final sample (N = 52). Most patients (n = 48) had a history of migraine based on International Headache Society criteria; 4 had primarily chronic tension-type headache, but with more migrainous features than permitted by International Headache Society criteria for a primary chronic tension-type headache diagnosis.
Results: Significant improvement was demonstrated for all headache diary measures, with significance levels ranging from P < .00001 for average intensity, duration, headache index (intensity x duration), peak intensity, headache days per week, and peak impairment, to P < .0033 for severe headache days per week, and P < .0051 for rescue medication days. During the last month of treatment, 71% of the patients completing the study showed at least a 50% reduction in headache index compared to baseline, and 59% had at least a 75% improvement. Visual analog scales completed at 4-week intervals showed significant improvement in patient ratings of overall headache status, quality of life, sleep, mood (P < .00001), and sexual function (P < .00053). Significant improvements were also observed in the Pain Disability Index (P < .00007), Beck Depression Inventory-II (P < .00001), Hamilton Rating Scale for Depression (P < .0008), and Hamilton Psychiatric Rating Scale for Anxiety (P < .00007). Headache indices for patients in the top quartile on the depression and anxiety scales (clinical depression/anxiety) did not differ from the other patients during baseline. However, patients who were depressed or anxious showed significantly more improvement over the course of 12 weeks of treatment (P < .0006 or less for the depression scales, P < .026 for anxiety). Common mild to moderate adverse events reported by 10% or more of the patients included fatigue, nausea, dry mouth, dizziness, sleep disturbance, blurred vision, irritability/nervousness, and sedation. Only 5 of the 52 patients discontinued the study due to adverse events: headache (2 patients), and nausea, sleep disturbance, and a drugged feeling (1 patient each).
Conclusions: These results provide preliminary support for the efficacy of nefazodone in the prophylaxis of chronic daily headache. In this sample, nefazodone was safe and generally well tolerated. Patient ratings of sexual function improved over the course of treatment, in contrast to what is generally observed with most antidepressants. Nefazodone may be particularly beneficial for patients with chronic daily headache and comorbid depression. Further research is indicated.
Micieli G, Cavallini A, Marcheselli S, Mailland F, Ambrosoli L, Nappi G
Int J Clin Pharmacol Ther. 2001;39:144-151
Objective: A double-blind, crossover study was carried out to compare the efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol (40 mg twice daily) in the prophylaxis of migraine without aura, and to identify possible predictors of therapeutic response by evaluating the symptomatological profile of individual migraine attacks and the autonomic cardiovascular response to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests.
Patients and methods: Forty migraineurs (10 males, 30 females) were randomized according to a 2-period (3-month), 2-treatment, crossover design. Efficacy was assessed using quantitative data recorded in the patient's headache diary. Data were evaluated using the Wallenstein's method.
Results: Both drugs showed a significant reduction in all the efficacy variables (headache attacks, days with headache, analgesic consumption) with no difference between treatments. Neither a bromocriptine test, nor a cold pressor test, nor the symptomatological profile of individual migraine attacks differed between the 2 groups of migraine patients. Ten patients experienced at least 1 adverse drug reaction during the first period of the crossover design, 5 being treated with alpha-dihydroergocryptine and 5 with propranolol.
Conclusions: It is concluded that alpha-dihydroergocryptine is an effective medication for migraine prophylaxis. The biochemical tests and the type of psychological profile cannot be used to predict drug response.
Saper JR, Winner PK, Lake AE
Headache. 2001;41:357-368
Objective: To assess effectiveness and safety of tizanidine hydrochloride tablets for the prophylaxis of chronic daily headache.
Background: Tizanidine hydrochloride is an alpha2-adrenergic agonist that inhibits the release and effectiveness of norepinephrine at both central sites (eg, the locus ceruleus) and the spinal cord. It acts as a central muscle relaxant and has antinociceptive effects. Preliminary research and retrospective analyses have suggested efficacy in treatment of both chronic tension-type headache and chronic daily headache with migrainous features.
Design: Thirty-nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed a 4-week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over 3 doses per day) by treatment week 4.
Results: The overall headache index through week 12 (headache frequency x average intensity x duration) declined significantly (P < .00000002), with a corresponding increase in mean percentage improvement from 49% for weeks 1 through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12 (P < .0182). During weeks 9 through 12, 67% had improved more than 50% compared to baseline. Overall headache frequency declined from 22.83 to 15.83 days per month (P < .00001), with frequency of severe headaches dropping from 7.52 to 3.58 days per month (P < .000035). Average headache intensity dropped from 1.83 to 1.07 (1-to-5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was reduced from 6.96 to 4.00 hours per headache (P < .00001). Improvement also occurred on visual analog scales of overall headache status, mood, sleep, quality of life (P <. 00001), and sexual function (P < .0075); as well as the Beck Depression Inventory-II (P < .00073). Mild-to-moderate adverse events reported by more than 10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients discontinued treatment due to adverse events: somnolence and dry mouth alone (n = 1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1). One patient had elevated liver enzymes that returned to normal after the drug was discontinued.
Conclusions: The results provide preliminary support for the efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic daily headache.
Diener HC, Hartung E, Chrubasik J, et al
Cephalalgia. 2001;21:120-128
This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between 2 and 6 migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from 3 to 2 in the ASA group and from 3 to 1 in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature.
Newman L, Mannix LK, Landy S, et al
Headache 2001;41:248-256
Objective: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine.
Background: Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine.
Methods: A randomized, double-blind, 3-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across 4 perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events.
Results: Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated 4 perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% vs 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 vs 4.0, P <.05) and menstrually associated migraine days (4.2 vs 7.0, P <.01) compared with placebo. More patients treated with naratriptan 1 mg were headache-free across all treated perimenstrual periods compared with placebo (23% vs 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan 2.5 mg was not statistically superior to placebo for any measure.
Conclusions: Naratriptan 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.
Wasiewski WW
J Child Neurol. 2001;16:71-78
Preventive therapy for migraine headache includes identification of migraine precipitants, possible adjustments in lifestyle, appropriate management of acute headache, and, when necessary, the use of pharmacologic agents. There are no well-controlled clinical trials with sufficient patient numbers to support the use of any agent in the prevention of migraine headache in children. Data on the use of amitriptyline and divalproex sodium in open-label studies suggest that these agents may be efficacious. The mechanism of action for these agents is unknown but may be related to the 5-hydroxytyptamine-2 (5-HT2) receptor antagonism or regulation of ion channels. A review of the pertinent literature on migraine prophylaxis in children is presented. Dosing guidelines are presented based on the limited data available and clinical experience.
Mathew NT, Rapoport A, Saper J, et al
Headache. 2001;41:119-128
Objective: To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura).
Study design and treatment: After screening, a 4-week, single-blind, placebo baseline period was followed by a 12-week, double-blind, treatment period. The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients were started on one 300-mg capsule of gabapentin or matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a 3-times-a-day dosing regimen.
Methods: The study hypothesis was defined a priori as a lower 4-week migraine rate during the second stabilization period for the gabapentin-treated patients as compared with the placebo-treated patients. The analyses were performed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor.
Results: At seven participating centers, 143 patients with migraine were randomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontinued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis were evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine episodes for a mean of about 21 years. At the end of the 12-week treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treated patients (P =.006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P =.008). The average number of days per 4 weeks with migraine was also statistically significant and favored gabapentin (P =.006) during stabilization period 2. The median change in 4-week headache rate was statistically significant as well (P =.013). The most frequently reported adverse events for both treatment groups were asthenia, dizziness, somnolence, and infection. Adverse events determined by the investigator to be associated with study drug resulted in patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness accounted for many of the premature withdrawals among those taking gabapentin.
Conclusion: Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mild to moderate somnolence and dizziness.
Hawken ER, Delva NJ, Lawson JS
Headache. 2001;41:92-96
To date, there have been no reports on the use of propranolol in electroconvulsive therapy (ECT)-induced migraine; we describe a 32-year-old woman who was successfully treated with propranolol for this condition. Over a course of ECT, the patient developed increasingly severe migraine which was refractory to treatment with acetaminophen, codeine, and naproxen. Sumatriptan did not relieve the headache and aggravated the nausea. Successful migraine relief was achieved with a combination of propranolol and naproxen, administered before and after ECT. Propranolol reduced blood pressure and decreased the heart rate, measured before and immediately after ECT. Propranolol, possibly in combination with naproxen, may be useful in both acute and prophylactic treatment of post-ECT migraine.
Schrader H, Stovner LJ, Helde G, Sand T, Bovim G
BMJ. 2001;322(7277):19-22
Objective: To determine the efficacy of an angiotensin converting enzyme inhibitor in the prophylaxis of migraine.
Design: Double-blind, placebo-controlled, crossover study.
Setting: Neurological outpatient clinic.
Participants: Sixty patients aged 19-59 years with migraine with 2 to 6 episodes a month.
Interventions: Treatment period of 12 weeks with one 10 mg lisinopril tablet once daily for 1 week then two 10 mg lisinopril tablets once daily for 11 weeks, followed by a 2-week wash out period. Second treatment period of 1 placebo tablet once daily for 1 week and then 2 placebo tablets for 11 weeks. Thirty participants followed this schedule, and 30 received placebo followed by lisinopril.
Main outcome measures:Primary end points: number of hours with headache, number of days with headache, number of days with migraine. Secondary end points: headache severity index, use of drugs for symptomatic relief, quality of life and number of days taken as sick leave, acceptability of treatment.
Results: In the 47 participants with complete data, hours with headache, days with headache, days with migraine, and headache severity index were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to 30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril compared with placebo. Days with migraine were reduced by at least 50% in 14 participants for active treatment vs placebo and 17 patients for active treatment versus run-in period. Days with migraine were fewer by at least 50% in 14 participants for active treatment vs placebo. Intention-to-treat analysis of data from 55 patients supported the differences in favour of lisinopril for the primary end points.
Conclusion: The angiotensin converting enzyme inhibitor, lisinopril, has a clinically important prophylactic effect in migraine.
Tanacetum parthenium L.): An Update of a Systematic Review
Ernst E, Pittler MH
Public Health Nutr. 2000;3:509-514
Objective: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy often advocated for the prevention of migraine. The aims of this systematic review are to update the evidence from rigorous clinical trials for or against the efficacy of feverfew for migraine prevention and to provide a safety profile of this herbal remedy.
Design: Literature searches were performed using the following databases: MEDLINE, Embase, Biosis, CISCOM and the Cochrane Library (all from their inception to December 1999). Only randomized, placebo-controlled, double-blind trials of feverfew monopreparations for the prevention of migraine in human subjects were included. All articles were read by 2 independent reviewers. Data were extracted in a predefined, standardized fashion. The methodological quality of the trials was evaluated by the Jadad score. For the assessment of safety issues, major reference texts were also consulted.
Results: Six trials met the inclusion/exclusion criteria. The majority favour feverfew over placebo. Yet important caveats exist. The data also suggest that feverfew is associated with only mild and transient adverse effects and few other safety concerns.
Conclusions: Feverfew is likely to be effective in the prevention of migraine. There are no major safety problems.
[Article in French]
Lanteri-Minet M, Alchaar H, Besson G, et al
Rev Neurol. 2000;156:1106-1112
A pharmacoepidemiological survey was conducted in order to understand the pattern of migraine prophylactic drug utilization by French physicians. Neurologists and primary care physicians completed a phone-mail-phone questionnaire which inquired about migraine prophylactic treatment. French neurologists and PCP made the same use of migraine prophylaxis in terms of indication, time interval between treatment onset and evaluation, and duration. The 2 most commonly chosen migraine prophylactic agents were dihydroergotamine and beta-blockers. This study also showed the importance of considering quality of life to evaluate efficacy of migraine prophylaxis.
Erdemoglu AK, Ozbakir S
Acta Neurol Scand. 2000;102:354-358
Objective: The efficacy and safety of valproic acid were assessed as a prophylactic agent in migraine patients who previously derived no significant benefit from conventional prophylactic medications for migraine.
Patients and methods: One hundred and twenty patients aged 23-58 years with the diagnosis of migraine without aura. Response to therapy was determined by using a headache calendar detailing the frequency and severity of attacks. Reduction of 50% or greater in the frequency or severity of headache was considered as improvement.
Results: Improvement was observed in headache frequency within 67% of patients. Headache severity had been improved in 60% of patients. The mean average dosage of valproic acid was 1250 mg daily. Most of the side effects are mild and tolerable.
Conclusion: These results suggest that valproic acid is effective and safe in the treatment of refractory migraine headache.
Russell AL, McCarty MF
Med Hypotheses. 2000;55:195-198
Following a fortuitous observation that migraine headaches ceased in a patient receiving glucosamine therapy for osteoarthritis, a further 10 patients with migraine or migraine-like vascular headaches, refractory to established preventive or abortive therapies, have been treated with daily oral glucosamine. After a lag of 4-6 weeks, a substantial reduction in headache frequency and/or intensity has been noted; in some cases, the benefit appears to be dose-dependent. Since glucosamine can be a rate-limiting precursor for mucopolysaccharide synthesis, it is germane to note previous reports that heparin and pentosan polysulfate may have migraine-preventive activity. There is reason to suspect that mast cells are central mediators of the neurogenic inflammation associated with migraine and cluster headaches. The heparin produced by mast cells may function to provide feedback down-regulation of mast cell activation, and exerts a range of other anti-inflammatory effects. We postulate that supplemental glucosamine can boost mast cell heparin synthesis -- perhaps correcting a functional heparin deficiency -- thereby preventing or ameliorating the neurogenic inflammation that mediates pain in vascular headache. Whether or not this idea has validity, a controlled study of glucosamine for migraine prophylaxis appears to be warranted.
Caruso JM, Brown WD, Exil G, Gascon GG
Headache. 2000;40:672-676
Objective: To determine the beneficial use of divalproex sodium as a prophylactic treatment for migraine in children.
Background: Previous studies for treatment of migraine in adults have shown a greater than 50% reduction in migraine attack frequencies. Few data exist, however, regarding the efficacy and safety of divalproex sodium use in children with migraine.
Methods: We studied the incidence of headache relief in our patients with migraine aged 16 years and younger treated with divalproex sodium prophylactically at our institution from July 1996 to December 1998 to determine medication dosage used, concomitant headache medications, and possible adverse effects.
Results: A total of 42 patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated with divalproex sodium for headache. All had a history of migraine with or without aura. Baseline headache frequency during a minimum 6-month period was 1 to 4 headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to 45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their abortive medications. After 4 months' treatment, 50% headache reduction was seen in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients became headache-free.
Conclusion: These results indicate divalproex sodium to be an effective and well-tolerated treatment for the prophylaxis of migraine in children.
Di Trapani G, Mei D, Marra C, Mazza S, Capuano A
Clin Ter. 2000;151:145-148
Objective: Gabapentin is an antiepileptic drug of new generation that increases brain GABA levels. We report the results of a 3-month randomised double-blind placebo-controlled study on the effects of gabapentin in the prophylaxis of patients with migraine meeting the IHS criteria.
Patients and methods: We treated 63 patients suffering from migraine with or without aura. Patients treated their attack at home using symptomatic drugs and clinical assessment was recorded on a diary. After a washout of 8 week from any other prophylactic treatment, all patients were treated with 1200 mg/day of gabapentin; this is our therapeutic plan: 400 mg/day from 1st to 3rd day, 800 mg/day from 4th to 6th day and 1200 mg/day from 7th day.
Results: No patients withdrew, gabapentin was well tolerated; adverse events (somnolence, dizziness, tremor, fatigue and ataxia) generally were transient and mild to moderate in severity and in 13 patients (27%) only occurred. At the end of treatment, in such case, we reported a significant reduction of frequency and intensity of migraine in 30 patients treated with gabapentin.
Discussion: Our observations indicate that gabapentin is well tolerated by patients and that reduces headache frequency and use of symptomatic drugs in both groups. Gabapentin shows to have an effective therapeutic action in the prophylactic treatment of migraine.
Adelman LC, Adelman JU, Von Seggern R, Mannix LK
Headache. 2000;40:572-580
Objective: To assess the efficacy of extended-release venlafaxine in the prophylaxis of migraine and chronic tension-type headache.
Background: Venlafaxine, a structurally novel antidepressant, is a selective serotonin-norepinephrine reuptake inhibitor. This study is the first to test the effects of extended-release venlafaxine on headaches.
Methods: Patients were evaluated on a retrospective basis. Fifty-six patients with chronic tension-type headache and 114 patients with migraine were prescribed extended-release venlafaxine. Nearly all the study subjects had been resistant to several previous preventive medications. Patients took venlafaxine for an average of 6 months with a median dose of 150 mg (range, 37.5 to 300 mg).
Results: The mean frequency of headaches in the group with chronic tension-type headache fell from 24.0 to 15.2 per month (P < .0001). The group with migraine showed a reduction from 16.1 to 11.1 headaches per month (P < .0001). The medicine was well tolerated.
Conclusions: This trial indicates that extended-release venlafaxine has potential in headache prophylaxis based on its efficacy and safety profile. We recommend a double-blind, placebo-controlled study to further assess the role of extended-release venlafaxine in headache prevention.
Hershey AD, Powers SW, Bentti AL, Degrauw TJ
Headache. 2000;40:539-549
Objective: To study the effectiveness of a standardized dose of amitriptyline, 1 mg/kg, for childhood headaches.
Background: Amitriptyline has been shown to be effective for the prophylaxis of migraine in adults. Studies in children, however, have been quite limited. In adults, the suggested effective dose range is 10 to 150 mg. In children, a standardized dosage is often not used, resulting in a dosage range in clinical practice that often varies from a very low dose to a dose equivalent to that used in adults.
Methods: Children with more than three headaches per month were treated with amitriptyline, slowly increasing the dose to 1 mg/kg per day. The frequency, severity, and duration of their headaches were initially evaluated and subsequently measured at each follow-up evaluation. Two hundred seventy-nine children had headaches occurring frequently enough to indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with amitriptyline. The average age at presentation was 12.0 (+/- 3.0) years. The ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1 (+/- 10.1) days per month. The average severity was 6.84 (+/- 1.67) on a 10-point pain scale. The average duration was 11.5 (+/- 15.0) hours. The most frequent diagnoses using International Headache Society criteria were migraine (60.6%), migraine with aura (7.9%), and tension-type headache (10.4%). Of these children, 146 have been seen for at least one follow-up examination, occurring on average 67.3 (+/- 32.3) days after beginning prophylactic treatment.
Results: A total of 84.2% of the children reported an overall perception of being better, while 11.6% reported being the same. The frequency of headaches improved to 9.2 (+/- 10.0) days per month. The average severity was reduced to 5.1 (+/- 2.1), and the average duration was reduced to 6.3 (+/- 11.1) hours. If daily or continuous headaches were excluded, the improvements were more marked. Minimal side effects were reported from these children and their families. Long-term evaluation (156 to 415 days) showed continued sustained improvement.
Conclusions: Amitriptyline is an effective prophylactic medication for children with frequent headaches. A standardized dosing regimen results in a significant number of children responding with minimal side effects. The children are able to tolerate this dosing scheme and demonstrate good adherence to a dosing schedule of once a day.
Luciani R, Carter D, Mannix L, Hemphill M, Diamond M, Cady R
Cephalalgia. 2000;20:122-126
Objective: To determine the role of naratriptan in preventing migraine headache when administered during prodrome.
Procedures:Baseline phase: patients recorded prodrome symptoms and time of onset, time when patient knew that headache was inevitable, time of onset and severity of headache.
Treatment phase: patients given naratriptan 2.5 mg to take at the time they knew headache was inevitable. Patients recorded prodrome symptoms and time of onset, time they knew headache was inevitable, time naratriptan administered, time of onset and severity of any headache. Patients treated 3 prodromes separated by at least 48 h.
Findings: Twenty patients completed both phases. During baseline phase, 59 prodromes were reported and all were followed by headache. Severity of headache: 5% mild, 51% moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of these, 38/63 (60%) were not followed by headache. Among headaches that occurred, the majority occurred within 2 h of naratriptan administration, suggesting that naratriptan is more effective in preventing headache if taken early in prodrome. Severity of 25 headaches: 44% mild, 24% moderate, 32% severe.
Conclusions: Naratriptan 2.5 mg appears to prevent migraine headache when given early in prodrome. If headache occurs, severity appears to be reduced.
What's new concerning the prophylaxis of migraine and other headaches? Find out in this easy-to-navigate compilation of MEDLINE and conference abstracts compiled by the editors at Medscape.
Saper JR, Lake AE, Tepper SJ
Headache. 2001;41:465-474
Objective: To assess effectiveness, tolerability, and safety of nefazodone as a prophylactic agent for chronic daily headache.
Background: Nefazodone is a potent, selective 5-HT2 antagonist with a distinct and atypical mechanism of action. The evolution of intermittent migraine to chronic daily headache has been linked to upregulation of 5-HT2 receptors as well as other factors. Other effective migraine prophylactic medications are also 5-HT2 antagonists. Although research has shown nefazodone to be an effective antidepressant with a good tolerability and safety profile, its potential role in headache prophylaxis has not been tested.
Design: This was a 2-center open-label study with a 4-week baseline, followed by 12 weeks of treatment with nefazodone at a median dose of 300 mg (mean, 303.66 +/- 65.57 mg; range, 100 to 450 mg, depending on tolerability). Potential patients were required to report more than 15 days of headache per month for at least 3 months prior to screening. Only patients with at least 15 days of recorded headache during baseline were included in the final sample (N = 52). Most patients (n = 48) had a history of migraine based on International Headache Society criteria; 4 had primarily chronic tension-type headache, but with more migrainous features than permitted by International Headache Society criteria for a primary chronic tension-type headache diagnosis.
Results: Significant improvement was demonstrated for all headache diary measures, with significance levels ranging from P < .00001 for average intensity, duration, headache index (intensity x duration), peak intensity, headache days per week, and peak impairment, to P < .0033 for severe headache days per week, and P < .0051 for rescue medication days. During the last month of treatment, 71% of the patients completing the study showed at least a 50% reduction in headache index compared to baseline, and 59% had at least a 75% improvement. Visual analog scales completed at 4-week intervals showed significant improvement in patient ratings of overall headache status, quality of life, sleep, mood (P < .00001), and sexual function (P < .00053). Significant improvements were also observed in the Pain Disability Index (P < .00007), Beck Depression Inventory-II (P < .00001), Hamilton Rating Scale for Depression (P < .0008), and Hamilton Psychiatric Rating Scale for Anxiety (P < .00007). Headache indices for patients in the top quartile on the depression and anxiety scales (clinical depression/anxiety) did not differ from the other patients during baseline. However, patients who were depressed or anxious showed significantly more improvement over the course of 12 weeks of treatment (P < .0006 or less for the depression scales, P < .026 for anxiety). Common mild to moderate adverse events reported by 10% or more of the patients included fatigue, nausea, dry mouth, dizziness, sleep disturbance, blurred vision, irritability/nervousness, and sedation. Only 5 of the 52 patients discontinued the study due to adverse events: headache (2 patients), and nausea, sleep disturbance, and a drugged feeling (1 patient each).
Conclusions: These results provide preliminary support for the efficacy of nefazodone in the prophylaxis of chronic daily headache. In this sample, nefazodone was safe and generally well tolerated. Patient ratings of sexual function improved over the course of treatment, in contrast to what is generally observed with most antidepressants. Nefazodone may be particularly beneficial for patients with chronic daily headache and comorbid depression. Further research is indicated.
Micieli G, Cavallini A, Marcheselli S, Mailland F, Ambrosoli L, Nappi G
Int J Clin Pharmacol Ther. 2001;39:144-151
Objective: A double-blind, crossover study was carried out to compare the efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol (40 mg twice daily) in the prophylaxis of migraine without aura, and to identify possible predictors of therapeutic response by evaluating the symptomatological profile of individual migraine attacks and the autonomic cardiovascular response to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests.
Patients and methods: Forty migraineurs (10 males, 30 females) were randomized according to a 2-period (3-month), 2-treatment, crossover design. Efficacy was assessed using quantitative data recorded in the patient's headache diary. Data were evaluated using the Wallenstein's method.
Results: Both drugs showed a significant reduction in all the efficacy variables (headache attacks, days with headache, analgesic consumption) with no difference between treatments. Neither a bromocriptine test, nor a cold pressor test, nor the symptomatological profile of individual migraine attacks differed between the 2 groups of migraine patients. Ten patients experienced at least 1 adverse drug reaction during the first period of the crossover design, 5 being treated with alpha-dihydroergocryptine and 5 with propranolol.
Conclusions: It is concluded that alpha-dihydroergocryptine is an effective medication for migraine prophylaxis. The biochemical tests and the type of psychological profile cannot be used to predict drug response.
Saper JR, Winner PK, Lake AE
Headache. 2001;41:357-368
Objective: To assess effectiveness and safety of tizanidine hydrochloride tablets for the prophylaxis of chronic daily headache.
Background: Tizanidine hydrochloride is an alpha2-adrenergic agonist that inhibits the release and effectiveness of norepinephrine at both central sites (eg, the locus ceruleus) and the spinal cord. It acts as a central muscle relaxant and has antinociceptive effects. Preliminary research and retrospective analyses have suggested efficacy in treatment of both chronic tension-type headache and chronic daily headache with migrainous features.
Design: Thirty-nine patients with more than 15 headache days per month (33 with migraine, 5 migrainous, 1 chronic tension-type) completed a 4-week baseline, with 31 completing a planned 12 weeks of treatment with tizanidine. Dosing was titrated from 2 mg at bedtime to a median daily dose of 14 mg (mean, 13.5; SD, 4.3; range, 4 to 20, divided over 3 doses per day) by treatment week 4.
Results: The overall headache index through week 12 (headache frequency x average intensity x duration) declined significantly (P < .00000002), with a corresponding increase in mean percentage improvement from 49% for weeks 1 through 4, to 65% for weeks 5 through 8, and 64% for weeks 9 through 12 (P < .0182). During weeks 9 through 12, 67% had improved more than 50% compared to baseline. Overall headache frequency declined from 22.83 to 15.83 days per month (P < .00001), with frequency of severe headaches dropping from 7.52 to 3.58 days per month (P < .000035). Average headache intensity dropped from 1.83 to 1.07 (1-to-5 scale), peak intensity declined from 2.37 to 1.40, and mean duration was reduced from 6.96 to 4.00 hours per headache (P < .00001). Improvement also occurred on visual analog scales of overall headache status, mood, sleep, quality of life (P <. 00001), and sexual function (P < .0075); as well as the Beck Depression Inventory-II (P < .00073). Mild-to-moderate adverse events reported by more than 10% of the patients included somnolence, asthenia, and dry mouth. Only 3 patients discontinued treatment due to adverse events: somnolence and dry mouth alone (n = 1), or in combination with either hyperkinesis (n = 1) or constipation (n = 1). One patient had elevated liver enzymes that returned to normal after the drug was discontinued.
Conclusions: The results provide preliminary support for the efficacy, safety, and tolerability of tizanidine in the prophylaxis of chronic daily headache.
Diener HC, Hartung E, Chrubasik J, et al
Cephalalgia. 2001;21:120-128
This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between 2 and 6 migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from 3 to 2 in the ASA group and from 3 to 1 in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature.
Newman L, Mannix LK, Landy S, et al
Headache 2001;41:248-256
Objective: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice daily compared with placebo as short-term prophylaxis of menstrually associated migraine.
Background: Approximately 60% of women with migraine report headaches associated with their menstrual cycles. Results from an open-label study suggest that short-term administration of sumatriptan is useful in the prophylaxis of menstrually associated migraine.
Methods: A randomized, double-blind, 3-arm, parallel-group, placebo-controlled study was conducted in women aged 18 years or older with a history of migraine with or without aura, as defined by the International Headache Society, of at least 6 months. Two dose strengths of naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were administered twice daily for 5 days starting 2 days prior to the expected onset of menses across 4 perimenstrual periods. End points included the number of menstrually associated migraines, total migraine days, peak headache severity, lost work/activity time, migraine-related quality of life, and incidence of adverse events.
Results: Overall, the intent-to-treat population comprised 206 women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n = 66); 171 women treated 4 perimenstrual periods. Significantly more perimenstrual periods per subject treated with naratriptan, 1 mg, were headache-free compared with placebo (50% vs 25%, P =.003). Naratriptan, 1 mg, significantly reduced the number of menstrually associated migraines (2.0 vs 4.0, P <.05) and menstrually associated migraine days (4.2 vs 7.0, P <.01) compared with placebo. More patients treated with naratriptan 1 mg were headache-free across all treated perimenstrual periods compared with placebo (23% vs 8%). No difference in headache severity was observed in breakthrough headaches. The incidence and severity of adverse events was similar across treatment groups. Naratriptan 2.5 mg was not statistically superior to placebo for any measure.
Conclusions: Naratriptan 1 mg, with tolerability similar to placebo, is an effective, short-term, prophylactic treatment for menstrually associated migraine.
Wasiewski WW
J Child Neurol. 2001;16:71-78
Preventive therapy for migraine headache includes identification of migraine precipitants, possible adjustments in lifestyle, appropriate management of acute headache, and, when necessary, the use of pharmacologic agents. There are no well-controlled clinical trials with sufficient patient numbers to support the use of any agent in the prevention of migraine headache in children. Data on the use of amitriptyline and divalproex sodium in open-label studies suggest that these agents may be efficacious. The mechanism of action for these agents is unknown but may be related to the 5-hydroxytyptamine-2 (5-HT2) receptor antagonism or regulation of ion channels. A review of the pertinent literature on migraine prophylaxis in children is presented. Dosing guidelines are presented based on the limited data available and clinical experience.
Mathew NT, Rapoport A, Saper J, et al
Headache. 2001;41:119-128
Objective: To compare gabapentin with placebo for use as a prophylactic agent in patients with migraine (with or without aura).
Study design and treatment: After screening, a 4-week, single-blind, placebo baseline period was followed by a 12-week, double-blind, treatment period. The 12-week treatment period consisted of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week titration phase, patients were started on one 300-mg capsule of gabapentin or matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1) to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study medication by the end of the titration period. Study medication was to be given on a 3-times-a-day dosing regimen.
Methods: The study hypothesis was defined a priori as a lower 4-week migraine rate during the second stabilization period for the gabapentin-treated patients as compared with the placebo-treated patients. The analyses were performed with the 4-week migraine rate at baseline as a covariate and center as a blocking factor.
Results: At seven participating centers, 143 patients with migraine were randomized in a 2:1 ratio and received either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients (24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98 gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the majority of patients discontinued due to adverse events (16 [16.3%] of 98 gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients included in the analysis were evenly balanced for age, sex, race, weight, and height. The majority of these patients were white (80 [92.0%] of 87) and women (72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of migraine episodes for a mean of about 21 years. At the end of the 12-week treatment phase, the median 4-week migraine rate was 2.7 for the gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5 for the placebo-treated patients (P =.006), compared with 4.2 and 4.1, respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P =.008). The average number of days per 4 weeks with migraine was also statistically significant and favored gabapentin (P =.006) during stabilization period 2. The median change in 4-week headache rate was statistically significant as well (P =.013). The most frequently reported adverse events for both treatment groups were asthenia, dizziness, somnolence, and infection. Adverse events determined by the investigator to be associated with study drug resulted in patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%) of 45 placebo-treated patients. Somnolence and dizziness accounted for many of the premature withdrawals among those taking gabapentin.
Conclusion: Gabapentin is an effective prophylactic agent for patients with migraine. In addition, gabapentin appears generally well tolerated with mild to moderate somnolence and dizziness.
Hawken ER, Delva NJ, Lawson JS
Headache. 2001;41:92-96
To date, there have been no reports on the use of propranolol in electroconvulsive therapy (ECT)-induced migraine; we describe a 32-year-old woman who was successfully treated with propranolol for this condition. Over a course of ECT, the patient developed increasingly severe migraine which was refractory to treatment with acetaminophen, codeine, and naproxen. Sumatriptan did not relieve the headache and aggravated the nausea. Successful migraine relief was achieved with a combination of propranolol and naproxen, administered before and after ECT. Propranolol reduced blood pressure and decreased the heart rate, measured before and immediately after ECT. Propranolol, possibly in combination with naproxen, may be useful in both acute and prophylactic treatment of post-ECT migraine.
Schrader H, Stovner LJ, Helde G, Sand T, Bovim G
BMJ. 2001;322(7277):19-22
Objective: To determine the efficacy of an angiotensin converting enzyme inhibitor in the prophylaxis of migraine.
Design: Double-blind, placebo-controlled, crossover study.
Setting: Neurological outpatient clinic.
Participants: Sixty patients aged 19-59 years with migraine with 2 to 6 episodes a month.
Interventions: Treatment period of 12 weeks with one 10 mg lisinopril tablet once daily for 1 week then two 10 mg lisinopril tablets once daily for 11 weeks, followed by a 2-week wash out period. Second treatment period of 1 placebo tablet once daily for 1 week and then 2 placebo tablets for 11 weeks. Thirty participants followed this schedule, and 30 received placebo followed by lisinopril.
Main outcome measures:Primary end points: number of hours with headache, number of days with headache, number of days with migraine. Secondary end points: headache severity index, use of drugs for symptomatic relief, quality of life and number of days taken as sick leave, acceptability of treatment.
Results: In the 47 participants with complete data, hours with headache, days with headache, days with migraine, and headache severity index were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to 30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril compared with placebo. Days with migraine were reduced by at least 50% in 14 participants for active treatment vs placebo and 17 patients for active treatment versus run-in period. Days with migraine were fewer by at least 50% in 14 participants for active treatment vs placebo. Intention-to-treat analysis of data from 55 patients supported the differences in favour of lisinopril for the primary end points.
Conclusion: The angiotensin converting enzyme inhibitor, lisinopril, has a clinically important prophylactic effect in migraine.
Tanacetum parthenium L.): An Update of a Systematic Review
Ernst E, Pittler MH
Public Health Nutr. 2000;3:509-514
Objective: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy often advocated for the prevention of migraine. The aims of this systematic review are to update the evidence from rigorous clinical trials for or against the efficacy of feverfew for migraine prevention and to provide a safety profile of this herbal remedy.
Design: Literature searches were performed using the following databases: MEDLINE, Embase, Biosis, CISCOM and the Cochrane Library (all from their inception to December 1999). Only randomized, placebo-controlled, double-blind trials of feverfew monopreparations for the prevention of migraine in human subjects were included. All articles were read by 2 independent reviewers. Data were extracted in a predefined, standardized fashion. The methodological quality of the trials was evaluated by the Jadad score. For the assessment of safety issues, major reference texts were also consulted.
Results: Six trials met the inclusion/exclusion criteria. The majority favour feverfew over placebo. Yet important caveats exist. The data also suggest that feverfew is associated with only mild and transient adverse effects and few other safety concerns.
Conclusions: Feverfew is likely to be effective in the prevention of migraine. There are no major safety problems.
[Article in French]
Lanteri-Minet M, Alchaar H, Besson G, et al
Rev Neurol. 2000;156:1106-1112
A pharmacoepidemiological survey was conducted in order to understand the pattern of migraine prophylactic drug utilization by French physicians. Neurologists and primary care physicians completed a phone-mail-phone questionnaire which inquired about migraine prophylactic treatment. French neurologists and PCP made the same use of migraine prophylaxis in terms of indication, time interval between treatment onset and evaluation, and duration. The 2 most commonly chosen migraine prophylactic agents were dihydroergotamine and beta-blockers. This study also showed the importance of considering quality of life to evaluate efficacy of migraine prophylaxis.
Erdemoglu AK, Ozbakir S
Acta Neurol Scand. 2000;102:354-358
Objective: The efficacy and safety of valproic acid were assessed as a prophylactic agent in migraine patients who previously derived no significant benefit from conventional prophylactic medications for migraine.
Patients and methods: One hundred and twenty patients aged 23-58 years with the diagnosis of migraine without aura. Response to therapy was determined by using a headache calendar detailing the frequency and severity of attacks. Reduction of 50% or greater in the frequency or severity of headache was considered as improvement.
Results: Improvement was observed in headache frequency within 67% of patients. Headache severity had been improved in 60% of patients. The mean average dosage of valproic acid was 1250 mg daily. Most of the side effects are mild and tolerable.
Conclusion: These results suggest that valproic acid is effective and safe in the treatment of refractory migraine headache.
Russell AL, McCarty MF
Med Hypotheses. 2000;55:195-198
Following a fortuitous observation that migraine headaches ceased in a patient receiving glucosamine therapy for osteoarthritis, a further 10 patients with migraine or migraine-like vascular headaches, refractory to established preventive or abortive therapies, have been treated with daily oral glucosamine. After a lag of 4-6 weeks, a substantial reduction in headache frequency and/or intensity has been noted; in some cases, the benefit appears to be dose-dependent. Since glucosamine can be a rate-limiting precursor for mucopolysaccharide synthesis, it is germane to note previous reports that heparin and pentosan polysulfate may have migraine-preventive activity. There is reason to suspect that mast cells are central mediators of the neurogenic inflammation associated with migraine and cluster headaches. The heparin produced by mast cells may function to provide feedback down-regulation of mast cell activation, and exerts a range of other anti-inflammatory effects. We postulate that supplemental glucosamine can boost mast cell heparin synthesis -- perhaps correcting a functional heparin deficiency -- thereby preventing or ameliorating the neurogenic inflammation that mediates pain in vascular headache. Whether or not this idea has validity, a controlled study of glucosamine for migraine prophylaxis appears to be warranted.
Caruso JM, Brown WD, Exil G, Gascon GG
Headache. 2000;40:672-676
Objective: To determine the beneficial use of divalproex sodium as a prophylactic treatment for migraine in children.
Background: Previous studies for treatment of migraine in adults have shown a greater than 50% reduction in migraine attack frequencies. Few data exist, however, regarding the efficacy and safety of divalproex sodium use in children with migraine.
Methods: We studied the incidence of headache relief in our patients with migraine aged 16 years and younger treated with divalproex sodium prophylactically at our institution from July 1996 to December 1998 to determine medication dosage used, concomitant headache medications, and possible adverse effects.
Results: A total of 42 patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated with divalproex sodium for headache. All had a history of migraine with or without aura. Baseline headache frequency during a minimum 6-month period was 1 to 4 headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to 45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their abortive medications. After 4 months' treatment, 50% headache reduction was seen in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients became headache-free.
Conclusion: These results indicate divalproex sodium to be an effective and well-tolerated treatment for the prophylaxis of migraine in children.
Di Trapani G, Mei D, Marra C, Mazza S, Capuano A
Clin Ter. 2000;151:145-148
Objective: Gabapentin is an antiepileptic drug of new generation that increases brain GABA levels. We report the results of a 3-month randomised double-blind placebo-controlled study on the effects of gabapentin in the prophylaxis of patients with migraine meeting the IHS criteria.
Patients and methods: We treated 63 patients suffering from migraine with or without aura. Patients treated their attack at home using symptomatic drugs and clinical assessment was recorded on a diary. After a washout of 8 week from any other prophylactic treatment, all patients were treated with 1200 mg/day of gabapentin; this is our therapeutic plan: 400 mg/day from 1st to 3rd day, 800 mg/day from 4th to 6th day and 1200 mg/day from 7th day.
Results: No patients withdrew, gabapentin was well tolerated; adverse events (somnolence, dizziness, tremor, fatigue and ataxia) generally were transient and mild to moderate in severity and in 13 patients (27%) only occurred. At the end of treatment, in such case, we reported a significant reduction of frequency and intensity of migraine in 30 patients treated with gabapentin.
Discussion: Our observations indicate that gabapentin is well tolerated by patients and that reduces headache frequency and use of symptomatic drugs in both groups. Gabapentin shows to have an effective therapeutic action in the prophylactic treatment of migraine.
Adelman LC, Adelman JU, Von Seggern R, Mannix LK
Headache. 2000;40:572-580
Objective: To assess the efficacy of extended-release venlafaxine in the prophylaxis of migraine and chronic tension-type headache.
Background: Venlafaxine, a structurally novel antidepressant, is a selective serotonin-norepinephrine reuptake inhibitor. This study is the first to test the effects of extended-release venlafaxine on headaches.
Methods: Patients were evaluated on a retrospective basis. Fifty-six patients with chronic tension-type headache and 114 patients with migraine were prescribed extended-release venlafaxine. Nearly all the study subjects had been resistant to several previous preventive medications. Patients took venlafaxine for an average of 6 months with a median dose of 150 mg (range, 37.5 to 300 mg).
Results: The mean frequency of headaches in the group with chronic tension-type headache fell from 24.0 to 15.2 per month (P < .0001). The group with migraine showed a reduction from 16.1 to 11.1 headaches per month (P < .0001). The medicine was well tolerated.
Conclusions: This trial indicates that extended-release venlafaxine has potential in headache prophylaxis based on its efficacy and safety profile. We recommend a double-blind, placebo-controlled study to further assess the role of extended-release venlafaxine in headache prevention.
Hershey AD, Powers SW, Bentti AL, Degrauw TJ
Headache. 2000;40:539-549
Objective: To study the effectiveness of a standardized dose of amitriptyline, 1 mg/kg, for childhood headaches.
Background: Amitriptyline has been shown to be effective for the prophylaxis of migraine in adults. Studies in children, however, have been quite limited. In adults, the suggested effective dose range is 10 to 150 mg. In children, a standardized dosage is often not used, resulting in a dosage range in clinical practice that often varies from a very low dose to a dose equivalent to that used in adults.
Methods: Children with more than three headaches per month were treated with amitriptyline, slowly increasing the dose to 1 mg/kg per day. The frequency, severity, and duration of their headaches were initially evaluated and subsequently measured at each follow-up evaluation. Two hundred seventy-nine children had headaches occurring frequently enough to indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with amitriptyline. The average age at presentation was 12.0 (+/- 3.0) years. The ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1 (+/- 10.1) days per month. The average severity was 6.84 (+/- 1.67) on a 10-point pain scale. The average duration was 11.5 (+/- 15.0) hours. The most frequent diagnoses using International Headache Society criteria were migraine (60.6%), migraine with aura (7.9%), and tension-type headache (10.4%). Of these children, 146 have been seen for at least one follow-up examination, occurring on average 67.3 (+/- 32.3) days after beginning prophylactic treatment.
Results: A total of 84.2% of the children reported an overall perception of being better, while 11.6% reported being the same. The frequency of headaches improved to 9.2 (+/- 10.0) days per month. The average severity was reduced to 5.1 (+/- 2.1), and the average duration was reduced to 6.3 (+/- 11.1) hours. If daily or continuous headaches were excluded, the improvements were more marked. Minimal side effects were reported from these children and their families. Long-term evaluation (156 to 415 days) showed continued sustained improvement.
Conclusions: Amitriptyline is an effective prophylactic medication for children with frequent headaches. A standardized dosing regimen results in a significant number of children responding with minimal side effects. The children are able to tolerate this dosing scheme and demonstrate good adherence to a dosing schedule of once a day.
Luciani R, Carter D, Mannix L, Hemphill M, Diamond M, Cady R
Cephalalgia. 2000;20:122-126
Objective: To determine the role of naratriptan in preventing migraine headache when administered during prodrome.
Procedures:Baseline phase: patients recorded prodrome symptoms and time of onset, time when patient knew that headache was inevitable, time of onset and severity of headache.
Treatment phase: patients given naratriptan 2.5 mg to take at the time they knew headache was inevitable. Patients recorded prodrome symptoms and time of onset, time they knew headache was inevitable, time naratriptan administered, time of onset and severity of any headache. Patients treated 3 prodromes separated by at least 48 h.
Findings: Twenty patients completed both phases. During baseline phase, 59 prodromes were reported and all were followed by headache. Severity of headache: 5% mild, 51% moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of these, 38/63 (60%) were not followed by headache. Among headaches that occurred, the majority occurred within 2 h of naratriptan administration, suggesting that naratriptan is more effective in preventing headache if taken early in prodrome. Severity of 25 headaches: 44% mild, 24% moderate, 32% severe.
Conclusions: Naratriptan 2.5 mg appears to prevent migraine headache when given early in prodrome. If headache occurs, severity appears to be reduced.
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