Approximately 26 million Americans suffer from migraines of which about 70 percent are women. Chances are if both parents suffered from migraines your chances of getting them are much higher and still much higher than average population if only one parent suffered from migraines.
This site is just for educational purposes and may help you in understanding some of your doctor's recommendations. Certainly your doctor wishes you to be educated.
The latest research abstracts are presented. Please do not let the abstracts overwhelm you. Although written for researchers, you can still pull out information that may be understood and make you more knowledgeable and offer you the opportunity to ask your doctor more questions.
Prices of triptans are also listed.
Medications that are used to treat migraines are also listed. Some super sites for additional overviews of migraine information are also provided.
: Arch Intern Med. 2003 May 12;163(9):1058-62. :
Comment in:
Arch Intern Med. 2003 May 12;163(9):1005.
Headache and the risk of stroke: a prospective observational cohort study among 35,056 Finnish men and women.
Jousilahti P, Tuomilehto J, Rastenyte D, Vartiainen E.
Department of Public Health, University of Helsinki, and the National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
pekka.jousilahti@ktl.fi
BACKGROUND: Previous studies have shown an increased risk of stroke among patients with migraine. However, very few data are available on the possible association between chronic unspecified headache and the risk of stroke. METHODS: A prospective cohort study including 35,056 randomly selected Finnish men and women aged 25 to 64 years at baseline who participated in a cardiovascular risk factor survey in 1972, 1977, 1982, or 1987. Self-reported headache, smoking, diabetes, blood pressure, weight, height, serum cholesterol level, and oral contraceptive use were recorded at baseline. During the follow-up, 2167 incident stroke events were ascertained with computer-based record linkage. RESULTS: Women reported headache twice as often as men (16.7% vs 8.9%). Among men, the headache-associated hazard ratios (95% confidence intervals) for stroke were 4.08 (2.10-7.93), 1.86 (1.33-2.59), and 1.24 (1.05-1.47) during 1, 5, and a maximum of 23 years of follow-up, respectively. Adjustment for the other risk factors decreased the hazard ratios only slightly. Among women, there was also a direct but statistically nonsignificant association between headache and the risk of stroke. CONCLUSIONS: Chronic headache is an independent predictor of stroke among men. Since the association between headache and the risk of stroke was particularly strong during a short follow-up, chronic headache may be a marker of the underlying disease process leading to acute stroke. The sex difference observed in this association may be due to a higher prevalence and a more heterogeneous etiology of headache in women compared with men.
Doc Ophthalmol. 2003 May;106(3):265-70.:
Effects of betaxolol and flunarizine on visual fields and intraocular pressure in patients with migraine.
Yarangumeli A, Comoglu S, Koz OG, Elhan AH, Kural G.
Ankara Numune Training and Research Hospital, 1st Eye Clinic, Ankara, Turkey.
alperyx@yahoo.com
Fifty-one patients with migraine were divided into four groups to investigate the effects of topical betaxolol and systemic calcium channel blocker flunarizine on visual fields (VF) and intraocular pressure (IOP). The first group (Group 0) was followed with no medications, topical betaxolol (bid) was precribed to the second group (Group B), oral flunarizine (10 mg daily) was prescribed to the third group (Group F), and the last group (Group BF) was assigned for combined betaxolol and flunarizine treatment. After a mean follow-up time of 4.2 +/- 1.2 months (3-6 months), IOP measurements and VF tests were repeated. Group B and Group BF were found to be statistically different from the other groups in terms of IOP reduction and VF improvement according to mean deviation and corrected pattern standard deviation indices in the second examinations. On the other hand, Group F and Group BF differed from the other two groups considering the improvement in migrainous complaints. VF findings which are probably influenced by perfusion problems due to vasospastic mechanisms in migraineurs, improved following topical betaxolol treatment. However, systemic use of flunarizine--a calcium channel blocker--did not seem to be effective on visual fields although it had beneficial effects on migraine.
Curr Pain Headache Rep 2003 Apr;7(2):135-8
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Topiramate in the treatment of cluster headache.
McGeeney BE.
Pain Management Group, Department of Neurology, Boston University School of
Medicine, 715 Albany Street, C329, Boston, MA 02118, USA.
bmcg@bu.eduCluster headache is a well-characterized, strictly unilateral headache with
cranial autonomic features and can be classified as episodic or chronic. Cluster
attacks reliably are short-lived, often have a clockwise regularity, and can
occur daily for weeks or months during an active cluster period. Pharmacologic
treatment for this disorder can be divided into abortive and prophylactic
agents. Prophylactic agents aim to quickly induce and maintain a remission.
Short-term prophylaxis may be attained with the use of steroids, ergotamine, or
methysergide, but these agents are not as suitable for continuous use. Verapamil
and lithium commonly are used for longer periods and other agents, such as
melatonin and baclofen, also are considered useful. There has been increased
interest in the use of anticonvulsants for pain syndromes such as primary
headache disorders. This includes topiramate use for cluster prophylaxis; a
number of open-label studies have had encouraging results. This article provides
an overview of topiramate and the open-label studies of this agent in the
prevention of cluster headache.
Curr Pain Headache Rep 2003 Feb;7(1):63-6
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The role of anticonvulsants in preventive migraine therapy.
Corbo J.
Department of Emergency Medicine, Jacobi Medical Center, 1400 Pelham
Parkway South, Bronx, NY 10462, USA.
jillcorbo@aol.comThe mainstay of migraine treatment is pharmacotherapy. There have been
numerous medications used to prevent migraine headaches, including b-blockers,
calcium-channel blockers, anticonvulsants, and nonsteroidal anti-inflammatory
drugs. Sodium valproate is the only antiepileptic drug approved by the Food and
Drug Administration for migraine prevention. Newer antiepileptics, including
gabapentin and topiramate, are being evaluated for their role in preventive
therapy.
The mechanism of action of antiepileptics is not fully understood, but
they all share a common role in enhancing gamma-aminobutyric acid-mediated
inhibition. This article reviews the role of anticonvulsants in preventive
migraine therapy.
Diagnosis and treatment of migraine.Despite recent advances in understanding the pathophysiology and treatment of
migraine, considerable uncertainty remains surrounding the diagnosis and treatment
of this disorder. This uncertainty is reflected in studies that show both
underdiagnosis and undertreatment of migraine. While the diagnosis can be assisted
by criteria from the International Headache Society, other approaches may be
useful in clinical practice. Treatment of migraine must be based on an individualized
patient strategy that integrates education, patient participation, and effective use
of pharmacological interventions. Many patients, despite self-treatment with simple
analgesics, continue to suffer considerable disability associated with their
migraines. Triptans, which are more effective at relieving migraine symptoms and
maintaining patient function than are nonspecific therapies, are used in only a
minority of patients with migraine. Treatment goals of rapid, complete relief with no
recurrence and minimal adverse effects can be achieved when effective therapy is
matched to individual patient goals. For prophylaxis, anticonvulsant drugs emerging
as effective options are being added to the armamentarium with traditional
compounds such as tricyclic antidepressants and beta-blockers.
Zanaflex(R) (tizanidine hydrochloride( prescription medication to treat muscle spasticity, a frequent
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at Rxbyfax-Tizanidine (Zanaflex)- 4 mg -150 -$99.44
Neurology 2002 Sep 10;59(5 Suppl 2):S8-13
:
Chronic headache: New advances in treatment strategies.Lake AE 3rd, Saper JR.
Michigan Head-Pain and Neurological Institute, 3120 ProfessionalDrive, Ann Arbor,
MI 48104, USA. aelake3rd@mhni.com
Chronic daily headache (CDH) affects approximately 4 to 5% of the population and
encompasses a number of different diagnoses, including transformed migraine,
chronic tension-type headache (TTH), new-onset daily persistent headache, and
hemicrania continua. Although the pathophysiology of CDH is still poorly understood,
some research has suggested that each of the various subtypes of CDH may have a
different pathogenesis. The goals of prophylactic therapy are to reduce the
frequency, severity, and duration of headache attacks; to improve responsiveness to
treatment of acute attacks; to improve function; and to reduce disability. However,
opinions differ as to exactly which are the best and most appropriate outcome
measures for prophylaxis.
Several pharmacologic treatment options exist, including
antidepressants, anticonvulsants, muscle relaxants, serotonin agonists, ergots,
serotonin antagonists, antianxiety agents, and other miscellaneous drugs. Tizanidine,
an alpha(2)-adrenergic agonist, has recently emerged as a promising prophylactic
adjunct for CDH, which implicates a central alpha(2)-adrenergic mechanism as an
important factor in the pathophysiology of CDH.
Tizanidine (Zanaflex) 4 mg 150 $99.44
Headache 2003 Apr;43(4):427
:
Chronic headache: new advances in treatment strategies.
Lake AE, Saper JR.Neurology. 2002;59(5 suppl 2):S8-S13. Chronic daily headache (CDH) affects
approximately 4 to 5% of the population and encompasses a number of
different diagnoses, including transformed migraine, chronic tension-type
headache (TTH), new-onset daily persistent headache, and hemicrania continua.
Although the pathophysiology of CDH is still poorly understood, some research
has suggested that each of the various subtypes of CDH may have a different
pathogenesis. The goals of prophylactic therapy are to reduce the frequency,
severity, and duration of headache attacks; to improve responsiveness to
treatment of acute attacks; to improve function; and to reduce disability.
However, opinions differ as to exactly which are the best and most appropriate
outcome measures for prophylaxis. Several pharmacologic treatment options
exist, including antidepressants, anticonvulsants, muscle relaxants, serotonin
agonists, ergots, serotonin antagonists, antianxiety agents, and other
miscellaneous drugs. Tizanidine, an alpha(2)-adrenergic agonist, has recently
emerged as a promising prophylactic adjunct for CDH, which implicates a
central alpha(2)-adrenergic mechanism as an important factor in the
pathophysiology of CDH. Comment: Drs. Lake and Saper provide a superb
overview of frequent headache, and taken with Dr. Silberstein's article
described above, the two reviews constitute the most up-to-date reviews on the
subject. SJT
Axert = Almotriptan ,
Ortho-McNeil: Axert influence on the migraine market"Axert will compliment Ortho-McNeil's epilepsy drug, Topamax (topiramate), which is currently in clinical trials for migraine prevention. The company intends to re-launch Axert in the second quarter of 2003. A regulatory submission is pending with Health Canada, and Janssen-Ortho will launch the product after it is approved there, anticipated to be later this year.
In 2001, the US Food and Drug Administration approved Axert, one of the newest migraine medications in the category of treatments known as triptans, for the acute treatment of migraine headaches with or without aura. Pharmacia originally launched Axert in the US in mid-2001, under a licensing agreement with Almirall. However, Pharmacia and Almirall have since agreed to terminate Pharmacia's rights to the license due to the company's merger with Pfizer. The product is also approved and marketed in the European Union, and was first launched in Spain in 2000."
Am J Health Syst Pharm 2002 Nov 15;59(22):2184-93 :
Efficacy and safety of almotriptan malate for migraine.
Balbisi EA.
College of Pharmacy and Allied Health Professions, St. John's University, Queens Hospital Center, Jamaica, NY, USA.
balbisie@stjohns.edu
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of almotriptan are reviewed. Migraine is a common disorder with a serious impact on quality of life. Newer serotonin-receptor agonists have been developed with the aim of improving pharmacokinetic characteristics. Almotriptan, a selective agonist of serotonin receptors 1B and 1D, carries FDA-approved labeling for use in the management of migraine with or without aura in adults. The efficacy and receptor affinity resemble those of sumatriptan, but almotriptan has a more favorable pharmacokinetic profile. It has a rapid onset of action, an oral bioavailability of 70-80%, and a longer half-life than sumatriptan. In clinical trials, almotriptan has been significantly more effective than placebo and as effective as sumatriptan. However, it has been associated with better tolerability and greater patient satisfaction. In clinical trials, the most commonly reported adverse effects were nausea, dry mouth, dizziness, somnolence, fatigue, vomiting, and paresthesia. Almotriptan is contraindicated in patients with known ischemic heart disease, coronary vasospasm, and other significant cardiovascular disorders. Almotriptan has a lower acquisition cost than other triptans and possibly lower overall health care costs because of a lower frequency of cardiovascular adverse effects. The recommended dose of almotriptan is one 6.25- or 12.5-mg tablet given at the onset of symptoms. Almotriptan is effective for the management of migraine and offers the potential for fewer adverse effects than other agents in its class.
J Clin Pharmacol 2002 Dec;42(12):1303-10 Related Articles, Links
Absolute bioavailability, pharmacokinetics, and urinary excretion of the novel antimigraine agent almotriptan in healthy male volunteers.
Jansat JM, Costa J, Salva P, Fernandez FJ, Martinez-Tobed A.
Department of Pharmacokinetics and Drug Metabolism, Almirall Prodesfarma S.A., Research Centre, Barcelona, Spain.
Absolute bioavailability, pharmacokinetics, and urinary excretion of almotriptan, a novel 5-HT(1B/1D) receptor agonist, were studied in 18 healthy males following single intravenous (i.v.) (3 mg), subcutaneous (s.c.) (6 mg), and oral (25 mg) doses. Volunteers received each dose in a randomized sequence separated by a 7-day washout. Blood and urine samples for pharmacokinetic evaluations were taken for up to 24 hours after dosing. The disposition kinetics of almotriptan after i.v. and s.c. administration showed biphasic decline described by a two-compartment model. The fastest disposition phase was well observed, although estimates of the rate constant showed high variability. After s.c. administration of almotriptan, the bioavailability was 100% with a time to maximum plasma concentration (tmax) of 5 to 15 minutes, whereas after oral administration, the bioavailability was about 70% with a tmax of 1.5 to 3.0 hours. No significant differences were observed between administration routes in the elimination half-life (t(1/2), obtaining mean values ranging from 3.4 to 3.6 hours. The volume of distribution, total clearance, and t(1/2) indicated that almotriptan was extensively distributed and rapidly cleared from the body irrespective of dose or route of administration. The primary route of elimination was renal clearance (approximately 50%-60% of total body clearance). About 65% of the i.v. and s.c. dose and 45% of the oral dose were excreted unchanged in urine in 24 hours, with nearly 90% of this in the first 12 hours. Renal clearance was approximately 2- to 3-fold that of the glomerular filtration rate in man, suggesting that almotriptan is eliminated in part by renal tubular secretion.
Cephalalgia 2002 Jul;22(6):453-61 :
Almotriptan is an effective and well-tolerated treatment for migraine pain: results of a randomized, double-blind, placebo-controlled clinical trial.
Dowson AJ, Massiou H, Lainez JM, Cabarrocas X.
Kings Headache Service, Kings College Hospital, Denmark Hill, London SE5 9RS, UK.
drandydowson@dowsona.fsnet.co.uk
Almotriptan is a novel and specific serotonin 5-HT1B/1D agonist for the acute treatment of migraine. This randomized, single-dose, double-blind, multicentre, study assessed the efficacy and safety of oral almotriptan (12.5 mg and 25 mg) in patients with migraine, and compared it with the standard treatment (sumatriptan 100 mg) and placebo. A total of 668 patients treated one migraine attack of moderate or severe intensity with study medication. The primary efficacy assessment was migraine pain relief, improvement from severe or moderate pain to mild or no pain, at 2 h after treatment. Response rates, stratified for variation in baseline pain levels, for both almotriptan doses were equivalent to sumatriptan and significantly better than placebo. Other efficacy assessments confirmed the equivalence of the almotriptan groups with the sumatriptan group. Almotriptan 12.5 mg was as well tolerated as placebo (P=0.493) and significantly better tolerated than sumatriptan (P<0.001), in terms of the overall incidence of adverse events. There was no statistically significant difference in the incidence of adverse events between almotriptan 25 mg and sumatriptan 100 mg (P=0.376). The results from this large clinical study indicate that the new, specific 5-HT1B/1D agonist, almotriptan, is an effective and well-tolerated treatment for migraine pain.
Headache 2003 Mar;43(3):300-301
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Almotriptan: a review of its use in migraine.
Keam S, Goa K, Figgitt D.Drugs. 2002;62(2):387-414 Almotriptan is a selective serotonin 5-HT(1B/1D)
receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in
a number of randomised, controlled trials in over 4800 adults with moderate or
severe attacks of migraine. Oral almotriptan has a rapid onset of action
(significant headache relief is observed 0.5 hours after administration of a
12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours.
The drug is significantly more effective than placebo as measured by a number
of parameters including 2-hour headache response and pain-free response rates.
Other symptoms of migraine, including nausea, photophobia and phonophobia, are
also alleviated by almotriptan. The efficacy of oral almotriptan appears to be
maintained over repeated doses for multiple attacks of migraine treated over a
long period (up to 1 year). High headache response rates were reported over all
attacks without tachyphylaxis. For the relief of single attacks of migraine, oral
almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients
given almotriptan report less concern with adverse effects than patients given
sumatriptan. The lower incidence of chest pain following treatment with
almotriptan than with sumatriptan may lead to a reduction in direct costs, with
fewer patients requiring management of chest pain. Almotriptan is well
tolerated. Most adverse events were of mild or moderate intensity, transient,
and generally resolved without intervention or the need for treatment
withdrawal. The most common adverse events associated with oral almotriptan
12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache,
somnolence, skeletal pain, vomiting and chest symptoms. The incidence of
adverse events did not differ from placebo and decreased in the longer term.
Almotriptan can be coadministered with drugs that share a common hepatic
metabolic path; in addition, dosage reduction is required only in the presence of
severe renal or hepatic impairment. CONCLUSIONS: Almotriptan is an
effective drug for the acute treatment of moderate or severe attacks of
migraine in adults. An oral dose of almotriptan 12.5mg has shown greater
efficacy than placebo; current data indicate that efficacy is similar to that of
oral sumatriptan 50mg, and is maintained in the long term (
Drug Saf 2003;26(2):93-107
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Tolerability of the triptans: clinical implications.
Nappi G, Sandrini G, Sances G.
University Centre for Adaptive Disorders and Headache, IRCCS 'C. Mondino
Foundation', University of Pavia, Pavia, Italy.
The triptans represent a relatively new class of compounds effective in the
treatment of migraine. The safety and tolerability of these drugs have been
extensively investigated since the first triptan (sumatriptan) became
commercially available. A report on a very large population of patients tested
during clinical trials and in postmarketing studies, confirms that these drugs are
safe and well tolerated when correctly used. Adverse events are frequently
reported, but are usually mild and only a few patients discontinue therapy
because of them. These adverse events include, in particular, the so-called
'triptan symptoms' (tingling, sensation of warmth, etc.). The exact mechanism of
chest symptoms reported by 20% of patients with migraine treated with
triptans remains unclear, but are exceptionally related to a cardiac mechanism.
CNS adverse events (i.e. somnolence) are also reported, but it is a matter of
debate whether they are related to the pharmacological properties (i.e.
lipophilicity) of the drug or are symptoms of the disease itself. The potential
risk for drug overuse must be taken into account when the triptans are given to
patients with a high frequency of migraine attacks. Clinical interaction of
triptans with other drugs metabolised in the liver may theoretically influence
the incidence of adverse events, but there is little evidence to support this
assumption. There is no evidence of a teratogenic risk of triptans in pregnant
women taking these drugs.
An open preference study with sumatriptan 50 mg and
zolmitriptan 2.5 mg in 100 migraine patients.
Understanding factors influencing patients' preference will improve guidance to
make rational choices in expanded symptomatic migraine treatment. The objective
of this open-label, cross-over study was to explore patients' preferences for
sumatriptan 50 mg vs. zolmitriptan 2.5 mg tablets, focusing on factors influencing
this preference. One hundred consecutive migraine patients attending our clinics
were asked to treat three attacks with each medication and then fill out a
preference questionnaire. Ninety-four migraineurs completed the trial and 42 (44%,
95% CI 34-58%) reported that they preferred zolmitriptan 2.5 mg over sumatriptan
50 mg tablets and 27 (29%, 20-38%) preferred sumatriptan 50 mg. The remaining
25 (27%, 18-36%) did not show any preference. For the initial treatment of the
attacks, there were more patients needing just one tablet of zolmitriptan 2.5 mg
compared with sumatriptan 50 mg (67 vs. 39%). The reasons for preference among
those 69 patients who had shown preference for either of the two triptans were: a
faster onset of action (speed of onset) (73%), a longer duration of the effects
(39%), fewer adverse events (35%) and lower price (13%). Only one-quarter of the
studied migraine population thought that sumatriptan 50 mg and zolmitriptan 2.5 mg
were equivalent, which suggests that most migraine patients differentiate between
triptans. A faster onset of action (speed of onset) was the most important reason
for preference.
Headache 2003 Mar;43(3):301
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Sumatriptan challenge in bipolar patients with and without
migraine: a neuroendocrine study of 5-HT1D receptor function.
Mahmood T, Silverstone T, Connor R, Herbison P.
Int Clin Psychopharmacol. 2002 Jan;17(1):33-36 An association between
bipolar disorder and migraine has been lately recognized and an abnormality of
central serotonergic function is suggested as the underlying neurophysiological
disturbance. To examine the role of serotonin in bipolar disorder and migraine,
we used the neuroendocrine challenge paradigm, and we chose sumatriptan, a
5HT1D agonist, as the pharmacological probe. We studied nine bipolar patients
with migraine, nine bipolar patients without it, seven migraine patients, and nine
matched normal controls. A post-hoc analysis showed subsensitivity of
serotonergic function, reflected in a blunted growth hormone response to
sumatriptan challenge in bipolar patients who also suffered from migraine.
Comment: Given regulatory and labelling concerns about the potential for
triptans to provoke serotonin syndrome, the apparent down-regulation of
serotonergic function in patients with bipolar disorder may suggest cause for
cautious optimism and encourage future study of triptans in these patients to
establish true causality or otherwise. A prospective trial of sumatriptan
injectable identified 1700 patients who repetitively used the triptan and were
concomitantly on selective serotonin reuptake inhibitor (SSRI) medication. No
serotonin syndrome was reported in any patient (Putnam GP, O'Quinn S,
Bolden-Watson CP, Davis RL, Gutterman DL, Fox AW. Migraine polypharmacy
and the tolerability of sumatriptan: a large-scale, prospective study.
Cephalalgia. 1999;19:668-675). Since SSRIs can rarely induce serotonin
syndrome alone, there is a significant difficulty in establishing a risk of
coadministration. DSM and SJT
Curr Pain Headache Rep 2002 Dec;6(6):480-5
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Prophylaxis for chronic daily headache and chronic migraine with
neuronal stabilizing agents.
Krusz JC.
Anodyne Pain Care,
5446 Glen Lakes Drive, Dallas, TX 75231, USA.
nodynia@swbell.net
Approaches to acute and prophylactic migraine and headache treatment are
evolving as our understanding of some of the underlying pathophysiology improves.
This article focuses on the emerging use of medications originally introduced for
the treatment of seizures (anticonvulsants) as primary therapy for eradicating or
reducing migraine and chronic daily headaches. A more accurate term for their
pharmacologic mechanisms, if they are used to treat headaches and pain disorders,
is neuromodulating or neuronal stabilizing agents. This term refers to their many
cellular actions to reduce pain transmission supraspinally, in the spinal cord, and in
the brainstem.
Comparison of triptan tablet consumption per attack: a
prospective study of migraineurs in Spain.
OBJECTIVES: To compare patient self-reported tablet consumption of rizatriptan
10 mg per attack (24 hours) with that of sumatriptan 50 mg, zolmitriptan 2.5 mg,
and naratriptan 2.5 mg on an unselected, prescription-based, Spanish migraine
population. METHODS: One hundred twenty community pharmacies recruited
patients with migraine, who used their pharmacies, to fill a triptan prescription. In
diaries, patients recorded baseline pain intensity and the number of triptan tablets
and additional medication taken per attack. Patients treated a maximum of three
attacks. Analysis of variance or the Student t test and chi-square or Fisher exact
tests were used for univariate comparisons. Hochberg corrections were used for
multiple-group comparisons. A generalized estimating equation method was used to
correct for within-subject correlation. Adjusted odds ratios (ORs) and 95%
confidence intervals (CIs) were calculated. RESULTS: Two hundred thirty-one
patients (84% women) treated 589 evaluable migraine attacks (sumatriptan, n = 135;
naratriptan, n = 90; zolmitriptan, n = 149; rizatriptan, n = 149). Triptan tablet
consumption per attack (mean +/- SD) for rizatriptan (1.24 +/- 0.56) was
significantly lower than that of sumatriptan (1.75 +/- 1.2; P< .05), zolmitriptan (1.61
+/- 0.86; P < .05), or naratriptan (1.46 +/- 0.62; P= .05). The average number of
triptan tablets taken and additional medication use increased according to baseline
pain severity. More attacks were treated with one tablet of rizatriptan (81.2%)
than with one tablet of sumatriptan (51.9%), zolmitriptan (55.7%), or naratriptan
(60%). The probability of using more than one triptan tablet per attack (24 hours)
was more than three times greater for sumatriptan (adjusted OR = 3.71; CI, 2.05 to
6.7; P = .001) and zolmitriptan (adjusted OR = 3.32; CI, 1.82 to 6.17; P = .001), and
more than two times greater for naratriptan (adjusted OR = 2.66; CI, 1.36 to 5.21; P
=.004) than for rizatriptan. CONCLUSIONS: Rizatriptan was associated with
significantly lower triptan tablet use and additional medication use per attack than
the other triptans. Additional randomized studies are needed to confirm the
conclusions of this study.
Effectiveness and safety of gabapentin in the preventive
treatment of migraine
INTRODUCTION. Migraine is a frequent and disabling pathological condition
with important socioeconomic repercussions. Recent studies have explored the
use of antiepileptic drugs in the prophylactic treatment of migraine.
Preliminary studies have shown that gabapentin is a drug that is effective and
well tolerated by patients. AIM. To evaluate the effectiveness and safety of
gabapentin in the prophylactic treatment of migraine. PATIENTS AND
METHODS. A prospective, open, multicentre, random clinical study, carried out
according to IHS criteria, which compares the effectiveness and safety of
gabapentin in 1,200 mg/day and 2,000 mg/day doses as a preventive treatment
for migraine over a 16 week period. RESULTS. Significant differences were
found in patients treated with gabapentin, as compared with their basal state,
in the following: a lower number of attacks (reduction in weeks 4, 10 and 16:
2.4 2.8, 2.9 2.9 and 3.1 2.9 attacks/month on a basal rate of 5.3 3.5
attacks/month), lower intensity (on a scale of 0 3 of increasing pain intensity:
basal rate: 2.7 0.4, week 4: 1.8 0.9, week 10: 1.7 0.9, week 16: 1.4 1.0) and how
long the pain lasts (basal rate 390 hours/month, week 4: 180 hours/month, week
10: 180 hours/month, week 16: 120 hours/month). No statistically significant
differences were found between doses of 1,200 or 2,000 mg/day. Mild adverse
effects were seen in 62 patients (37.8%): drowsiness (22.6%), asthenia (7.9%),
dizziness (4.9%), abdominal pain (3.7%) and dazedness (3.7%). No serious
adverse events occurred. CONCLUSIONS. Gabapentin can be considered an
effective and safe drug in the preventive treatment of migraine
Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed
results and methods of a meta-analysis of 53 trials.
The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute
migraine drugs. Soon, seven different triptans will be clinically available at 13
different oral doses, making evidence-based selection guidelines necessary.
Triptan trials have similar designs, facilitating meta-analysis. We wished to
provide an evidence-based foundation for using triptans in clinical practice, and
to review the methodological issues surrounding triptan trials. We asked
pharmaceutical companies and the principal investigators of
company-independent trials for the 'raw patient data' of all double-blind,
randomized, controlled, clinical trials with oral triptans in migraine. All data
were cross-checked with published or presented data. We calculated summary
estimates across studies for important efficacy and tolerability parameters,
and compared these with those from direct, head-to-head, comparator trials.
Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089
patients met the criteria for inclusion. Mean results (and 95% confidence
intervals) for sumatriptan 100 mg, the first available and most widely
prescribed oral triptan, are 59% (57-60) for 2 h headache response
(improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h
pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain
free by 2 h and no headache recurrence or use of rescue medication 2-24 h
post-dose), and 67% (63-70) for consistency (response in at least two out of
three treated attacks); placebo-subtracted proportions for patients with at
least one adverse event (AE) are 13% (8-18), for at least one central nervous
system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared
with these data: rizatriptan 10 mg shows better efficacy and consistency, and
similar tolerability; eletriptan 80 mg shows better efficacy, similar
consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy
at 2 h but better sustained pain-free response, consistency, and tolerability;
sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower
efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40
mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials
that directly compared triptans show the same overall pattern. We received no
data on frovatriptan, but publicly available data suggest substantially lower
efficacy. The major methodological issues involve the choice of the primary
endpoint, consistency over multiple attacks, how to evaluate headache
recurrence, use of placebo-subtracted proportions to control for across-study
differences, and the difference between tolerability and safety. In addition,
there are a number of methodological issues specific for direct comparator
trials, including encapsulation and patient selection. At marketed doses, all oral
triptans are effective and well tolerated. Differences among them are in
general relatively small, but clinically relevant for individual patients.
Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the
highest likelihood of consistent success. Sumatriptan features the longest
clinical experience and the widest range of formulations. All triptans are
contra-indicated in the presence of cardiovascular disease.
New insights into the molecular actions of serotonergic
antimigraine drugs
Migraine is a painful and debilitating neurological disorder that affects
approximately 10% of the adult population in Western countries. Sensitization
and activation of the trigeminal ganglia nerves that innervate the meningeal
blood vessels is believed to play an important role in the initiation and
maintenance of migraine pain. In this capacity, release of the neuropeptide
calcitonin gene-related peptide (CGRP) and the resultant neurogenic
inflammation is thought to underlie the pathophysiology of migraine. Largely due
to the success of the serotonin Type 1 migraine drugs such as sumatriptan,
migraine pathology and therapy has become a focus of intensive clinical and
physiological research during the past decade. The effectiveness of these drugs
is thought to be due to their ability to block the stimulated secretion of
neuropeptides from trigeminal nerves to break the vicious nociceptive cycle of
migraine. A component of this nociceptive cycle involves activation of
mitogen-activated protein kinase signaling pathways. Indeed, activation of
mitogen-activated protein kinase pathways can increase CGRP neuropeptide
synthesis and secretion. Recently, the serotonin Type 1 agonists have been
shown to cause a prolonged increase in intracellular Ca(2+) in trigeminal ganglia
neurons and an increased phosphatase activity that can repress stimulated CGRP
secretion and transcription. Identification of molecular signaling events in
migraine pathology and therapy has provided new insight into the pharmacology
and signaling mechanisms of sumatriptan and related drugs, and may provide the
foundation for development of novel treatments for migraine.
Chronic headache: New advances in treatment strategies.
Chronic daily headache (CDH) affects approximately 4 to 5% of the population
and encompasses a number of different diagnoses, including transformed
migraine, chronic tension-type headache (TTH), new-onset daily persistent
headache, and hemicrania continua. Although the pathophysiology of CDH is still
poorly understood, some research has suggested that each of the various
subtypes of CDH may have a different pathogenesis. The goals of prophylactic
therapy are to reduce the frequency, severity, and duration of headache
attacks; to improve responsiveness to treatment of acute attacks; to improve
function; and to reduce disability. However, opinions differ as to exactly which
are the best and most appropriate outcome measures for prophylaxis. Several
pharmacologic treatment options exist, including antidepressants,
anticonvulsants, muscle relaxants, serotonin agonists, ergots, serotonin
antagonists, antianxiety agents, and other miscellaneous drugs. Tizanidine, an
alpha(2)-adrenergic agonist, has recently emerged as a promising prophylactic
adjunct for CDH, which implicates a central alpha(2)-adrenergic mechanism as
an important factor in the pathophysiology of CDH.
Do butalbital-containing products have a role in the management
of migraine?
STUDY OBJECTIVE: To evaluate the role of butalbital-containing products in
the management of migraine. METHODS: Qualitative systematic search using
MEDLINE (January 1966-November 2001), review of the United States
Headache Consortium's evidence-based guidelines for migraine treatment, and
review of other pertinent literature. RESULTS: Over 28 million people suffer
with migraine, yet this illness is less than optimally diagnosed and managed.
Between 14% and 36% of diagnosed migraineurs are prescribed
butalbital-containing products, often as initial therapy. However, the only
identified controlled trial of these drugs for migraine treatment showed that
butalbital-containing products were inferior to butorphanol. The consortium's
guidelines specifically discourage administration of butalbital-containing
products for migraine. In addition, other published literature highlights the
frequent adverse consequences of butalbital-containing products for
migraineurs, such as poor migraine control, disability, drug-induced headaches,
and withdrawal symptoms. CONCLUSION: Although butalbital-containing
products commonly are prescribed for migraine, no evidence in the literature
demonstrates their benefit over other agents or placebo. Drugs with proven
migraine efficacy, as listed in the consortium's evidence-based guidelines,
should be prescribed instead.
A randomized trial of divalproex sodium extended-release tablets
in migraine prophylaxis.
OBJECTIVE: To evaluate the efficacy and safety of extended-release divalproex
sodium compared with placebo in prophylactic monotherapy treatment of migraine
headache. METHODS: This was a double-blind, randomized, placebo-controlled,
parallel-group study. Subjects with more than two migraine headache attacks during
a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive
either extended-release divalproex sodium or matching placebo once daily for 12
weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose
was then increased to 1,000 mg once daily with an option, if intolerance occurred, to
permanently decrease the dose to 500 mg during the second week. Reduction from
baseline in 4-week migraine headache rate was the primary efficacy variable.
Migraine headaches separated by a < 24-hour headache-free interval were counted
as single migraines in calculating migraine headache rates. Tolerance and safety
were also evaluated. RESULTS: The mean reductions in 4-week migraine headache
rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex
sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006);
reductions with extended-release divalproex sodium were significantly greater than
with placebo in all three 4-week segments of the treatment period. No significant
differences were detected between treatment groups in either the overall
incidence or in the incidence of any specific treatment-emergent adverse event; 8%
of subjects treated with extended-release divalproex sodium and 9% of those
treated with placebo discontinued for adverse events. CONCLUSION:
Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and
easy-to-use once-a-day prophylactic antimigraine medication.
Efficacy and tolerability in migraine prophylaxis of flunarizine in
reduced doses: a comparison with propranolol 160 mg daily.
This was a phase-IV double-blind equivalence trial designed to assess the efficacy
and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5 mg o.d.=FLU
5 mg) in the prophylaxis of migraine, in comparison with slow-release propranolol
(160 mg o.d.). A total of 808 subjects were treated in a treatment period of 16
weeks. 142 subjects discontinued the trial prematurely, mainly because of adverse
events (n=58). The mean attack frequency in the double-blind period was 2.0 for the
FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for the propranolol group. The
mean attack frequency in the last 28 days of the double-blind period was 1.8 for
FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for propranolol. Both flunarizine groups were at
least as effective as propranolol (P<0.001 in one-sided test). The percentage of
responders (defined as subjects for whom attack frequency decreased by at least
50% compared to run-in) in the last 28 days of the double-blind period was 46%
(118/259) for FLU 5 mg, 53% (141/264) for FLU 10 mg, and 48% (125/258) for
propranolol. Statistical analysis showed that FLU 10 mg is at least as effective as
propranolol (P<0.001) and showed a trend for noninferiority of FLU5 and propranolol
(P=0.053). No statistically significant differences between the treatment groups
were found for any of the secondary parameters. Overall, 190 subjects reported
one or more adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg
group, 76 (27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group.
The results of this equivalence trial show that 10 mg flunarizine daily with a
drug-free weekend is at least as effective as 160 mg propranolol in the prophylaxis
of migraine for all evaluated parameters (one-sided equivalence tests) after 16
weeks of treatment. In addition, 5 mg flunarizine proves to be at least as effective
as 160 mg propranolol when looking at the mean attack frequency for both the
whole double-blind period and the last 28 days of treatment. However, in the
analysis of responders, 160 mg propranolol seems to be slightly better than 5 mg
flunarizine. In addition, no significant differences between the three treatments
were found with regard to safety: all three treatments were generally
well-tolerated and safe.
Treatment of paediatric headache.
Lewis DW, Scott D, Rendin V.
Division of Pediatric Neurology, 850 Southampton Ave., Norfolk, Virginia 23510,
USA. dLewis@chkd.com
Headaches are very common during childhood and become increasingly frequent
during adolescence. The diagnosis of primary headache disorders (e.g., migraine and
tension-type headache) rests principally on clinical criteria as set forth by the
International Headache Society. Treatment options include acute or episodic
measures, prophylactic agents and non-pharmacological or behavioural interventions.
From review of available evidence, the most efficacious acute treatments of
paediatric migraine include the non-steroidal anti-inflammatory agent ibuprofen at
7.5 - 10 mg/kg/dose or nasal sumatriptan at doses of 5 or 20 mg. For those patients
with headaches that occur with sufficient frequency and severity to warrant daily
prophylaxis, controlled data are limited. Agents which are likely to be beneficial
include amitriptyline, flunarizine (not available in the US) and cyproheptadine.
Clinical experience with the anti-epileptic agents topiramate and valproate suggests
an expanding role for the prevention of paediatric migraine in the future.
Flunarizine (trade name Sibelium) a calcium channel blocker, (appears to be the most effective drug in treating Alternating Hemiplegia of Childhood. Flunarizine reduces the severity and duration, but rarely the frequency.0
Headache 2002 Jun;42(6):515-8
:
Olanzapine in the treatment of refractory migraine and chronic
daily headache.
Silberstein SD, Peres MF, Hopkins MM, Shechter AL, Young WB, Rozen
TD.
Jefferson Headache Center, Department of Neurology,
Thomas Jefferson
University Hospital, Philadelphia, Pa.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.
Treatment of idiopathic headache in childhood - recommendations
of the German Migraine and Headache Society (DMKG)]
Evers S, Pothmann R, Uberall M, Naumann E, Gerber WD.
Klinik und Poliklinik fur Neurologie, Westfalische Wilhelms-Universitat Munster,
Germany. everss@uni-muenster.de
According to the principles of evidence-based medicine, the controlled studies on
the treatment of idiopathic headache in childhood have been analysed and compiled
to treatment recommendations. For the acute treatment of migraine attacks or
tension-type headache, ibuprofen (10 mg per kg body weight) or acetaminophen (15
mg per kg body weight) are recommended with highest evidence, intranasal
sumatriptan (10 to 20 mg) can be given as second choice. For the prophylaxis of
migraine, betablockers (propranolol and metoprolol), flunarizine, and valproic acid
are recommended. Flunarizine is the drug of first choice in the treatment of
migraine-related disorders. No controlled studies are available for the treatment of
further headache types. First line methods for the non-drug treatment of headache
in childhood are relaxation therapies, biofeedback, and specific training schedules
Abortive Medications for Migraines
Prices at RxbyFax
Amerge®(naratriptan)-2.5mg-$12.60 per pill
Axert® (almotriptan)-not available
Frova® (frovatriptan)-not available
Imitrex®(sumatriptan)-100mg-$11.64 per pill
Maxalt® (rizatriptan)-10mg-$12.21 per pill or per wafer
Zomig®(zolmitriptan)-2.5 mg.-$10.48
Prices at well known US pharmacy
Amerge®(naratriptan)-2.5mg-$19.35 per pill
Axert® (almotriptan)12.5-$12.17 per pill
Frova® (frovatriptan)-2.5 mg $16.00 per pill
Imitrex®(sumatriptan)-100mg-$16.67 per pill
Maxalt® (rizatriptan)-10mg-$17.34 per pill
Zomig®(zolmitriptan)-2.5 mg.-$16.50
CATAPRES®
Ergot
ergotamine (Ergomar)
Wigraine
BELLERGAL-S®
Phenothiazines
Domperidone
Prochlorperazine
Metoclopramide
Reglan
Dihydoergotamine
dihydroergotamine (D.H.E. 45)
Migranal®
Analgesic Combinations
Excedrin Migraine®, Midrin®
Preventative Medications for Migraines
Beta blockers
ATENOLOL-® and Tenoretic® are brand names of Atenolol.
CORGARD
Inderal® (propranolol)-
Blocadren ® (timolol maleate)-not available
metoprolol- Lopressor-
metoprolol- generic
Calcium-channel blockers
Cardizem® (diltiazem)-
Procardia®(nifedipine)-
Antidepressants
Prozac® (fluoxetine)-
Paxil® (paroxetine) -
Zoloft® (sertraline)-
Anticonvulsants
Depakote® (valproic acid or divalproex sodium)-.
NSAIDs
Orudis® (ketoprofen) -Oruvail)
Aleve® (naproxen sodium).-
OTHER RESOURCES
MAYO CLINIC
Triptans. Sumatriptan (Imitrex) was the first drug
specifically developed to treat migraines. It mimics
the action of serotonin by binding to serotonin
receptors and causing blood vessels to constrict.
Migraines at work(Australian site)
National Heachache foundation
JAMA Migraine Headache Information Center
NINDS headache information
ACHE
Resources for migraine information |
American Headache society
