Topamax(topiramate) for Migraines

Topamax and migrainesThis webpage contains the current research for the anticonvulsant topamax and migraine headaches. U.S. FDA Approves TOPAMAX(R) For Migraine Prophylaxis, Providing Hope For Those Who Suffer From Migraine Headaches and reduce the frequency of migraines. Over 14,000,000 millions suffer from migraines.

So far research suggests it is helpful in binge eating, alcohol treatment, and biolar mood stabilization and weight loss. It is a treasure chest.

This webpage is courtesy of Rxbyfax for educational purposes only. Only your doctor can recommend Topamax for your migraines, bipolar, weight loss or on label epilepsy. Hopefully you will find it fascinating how one drug can possibly help so many conditions and suggest that some forms of each condition that are refractory may be have a relationship to each other. Please skim the research abstracts and don't get overwhelmed. They are like a jigsaw puzzle and watching pieces gradually fit together.

The writer is currently on topamax for bipolar II.

Epilepsy Drug Fights Migraine
" By using about half the normal dose prescribed for epilepsy, researchers found treatment with the drug Topamax cut the number of migraine episodes in half for more than 50% of the migraine sufferers. "

Epilepsy Drug Could Help Prevent Migraines: Study Mon Sep 23,10:32 AM ET
" Researchers now believe that migraines, like epilepsy, are a central nervous system disorder, which is why anti-epilepsy drugs have been tested against the headaches, Silberstein explained. In his study, patients were given 50 milligrams (mg), 100 mg or 200 mg daily of Topamax, or placebo. Those taking the 100 mg and 200 mg doses had the greatest response...Silberstein said Topamax was promising, but cautioned that "no drug works in everybody." "

: JAMA. 2004 Feb 25;291(8):965-73. : Topiramate for migraine prevention: a randomized controlled trial.
Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D; MIGR-002 Study Group.
Nashville Neuroscience Group, Nashville, Tenn 37203, USA.
jbrandes@nashvilleneuroscience.com CONTEXT: Small open-label and controlled trials suggest that the antiepileptic drug topiramate is effective for migraine prevention. OBJECTIVE: To assess the efficacy and safety of topiramate for migraine prevention in a large controlled trial. DESIGN, SETTING, AND PATIENTS: A 26-week, randomized, double-blind, placebo-controlled study was conducted during outpatient treatment at 52 North American clinical centers. Patients were aged 12 to 65 years and had a 6-month history of migraine (International Headache Society criteria) and 3 to 12 migraines a month but no more than 15 headache days a month during a 28-day prospective baseline phase. INTERVENTIONS: After a washout period, patients meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or maximum tolerated dose, whichever was less. Patients continued receiving that dose for 18 weeks. MAIN OUTCOME MEASURES: The primary efficacy measure was change from baseline in mean monthly migraine frequency. Secondary efficacy measures included responder rate (proportion of patients with > or =50% reduction in monthly migraine frequency), reductions in mean number of monthly migraine days, severity, duration, and days a month requiring rescue medication, and adverse events. The month of onset of preventive treatment action was assessed. RESULTS: Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy assessment and comprised the intent-to-treat population. Mean monthly migraine frequency decreased significantly for patients receiving topiramate at 100 mg/d (-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1). Statistically significant reductions (P<.05) occurred within the first month with topiramate at 100 and 200 mg/d. The responder rate was significantly greater with topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P<.001), and 200 mg/d (47%, P<.001) vs placebo (23%). Reductions in migraine days were significant for the 100-mg/d (P =.003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups. Adverse events resulting in discontinuation in the topiramate groups included paresthesia, fatigue, and nausea. CONCLUSION: Topiramate showed significant efficacy in migraine prevention within the first month of treatment, an effect maintained for the duration of the double-blind phase.

Headache. 2003 Nov-Dec;43(10):1080-4. : Topiramate as an adjunctive treatment in migraine prophylaxis.
Martinez HR, Londono O, Cantu-Martinez L, del Carmen Tarin L, Castillo CD.
Neurology Service, Hospital Universitario, Monterrey, NL, Mexico.

BACKGROUND: Anticonvulsants now are commonly used for headache prevention. Topiramate, one of the newer anticonvulsants, recently has been demonstrated to be effective as monotherapy for migraine prophylaxis. OBJECTIVE: To assess the efficacy, safety, and tolerability of topiramate as adjunctive prophylactic therapy for migraine. MATERIAL AND METHODS: A prospective trial involving patients with more than 3 migraine attacks per month was performed. Patients continued their usual prophylactic treatment. Baseline analgesic use and frequency and duration of migraine attacks were recorded. A 4-point visual analog scale evaluated severity. Laboratory tests, electrocardiogram, and computed tomography or magnetic resonance imaging were performed before study entry. After informed consent was obtained, patients were instructed to take 25 mg of topiramate per day, with 25- to 50-mg weekly increments to a maximum of 100 mg per day. Safety was assessed at the first month; tolerability and efficacy were assessed every week for the first month and then every month for 3 months. Effectiveness was assessed by comparing baseline and on-treatment migraine status, and data were analyzed by the Fisher exact test. RESULTS: Twenty-five women and 11 men (mean age, 44 years) were evaluated. Existing prophylactic treatment was either propranolol or flunarizine (or both) in 80% of the patients. At 3 months of therapy with topiramate, headache frequency decreased from 17 to 3 episodes per month, headache duration from 559 to 32 minutes, and intensity from 9 to 1 by visual analog scale (P <.001). Improvement in frequency and severity of migraine was observed in 83% of patients. Slight or no changes in headache were observed in 6 patients. Tolerability was good in 30 patients. The most common side effects were acroparesthesias, weight loss, sleepiness, and headache worsening. No adverse interaction with propranolol or flunarizine was observed. CONCLUSIONS: These results suggest that topiramate is efficacious and safe as an adjunctive treatment in patients with migraine whose prior response to prophylactic management has been less than satisfactory.

Cephalalgia. 2003 Oct;23(8):820-4. : Topiramate in the treatment of chronic migraine.
Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L.
Department of Neurological Sciences, University of Ancona, Ancona, Italy, IRCCS, S. Lucia, Rome, Italy.
masilvestrini@libero.it
The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache +/- SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.

Neurologia. 2003 Sep;18(7):364-7. : Topiramate for patients with refractory migraine: an observational, multicenter study in Spain.
Pascual J, Sanchez del Rio M, Mateos V, Lainez JM, Hernandez-Gallego J, Leira R, Jimenez MD.
University Hospital Marques de Valdecilla (UC), Santander.
juliopascual@telefonica.net
INTRODUCTION: The efficacy of current preventive migraine treatments is limited. In addition, tolerability problems are not infrequent. OBJECTIVES: To check our experience with topiramate in the treatment of patients with refractory migraine. PATIENTS AND METHODS: We offered treatment with topiramate to patients with the diagnosis of International Headache Society (IHS) migraine who had not responded to or tolerated beta-blockers, amitriptyline, flunarizine and/or valproate. This series is made up of 115 patients (88 women), between 16 and 81 years. Most of them (n=79) fulfilled the Silberstein et al. criteria for transformed migraine. The parameters analyzed were "response" (reduction in migraine frequency>50%), excellent response (>75%) and tolerability. RESULTS: After 3 months, the maintenance doses of topiramate ranged from 25 to 400 mg, though most patients took 100 mg. Twenty-four (21%) patients withdrew due to adverse events, mostly cognitive difficulties, that had already occurred with doses as low as 25-50 mg, while 26 (23%) found topiramate ineffective. The remaining 65 (56%) patients responded, 34 with excellent response. Sixteen patients (10 obese) lost weight (3-13 kg). CONCLUSIONS: Topiramate seems to be a good therapeutic option for about half of the patients with refractory migraine. In these patients response is usually excellent. Intolerance due to adverse events appears in one-fifth of the cases early and at low doses.

CNS Spectr. 2003 Jun;8(6):428-32. : Topiramate in the preventive treatment of episodic migraine: a combined analysis from pilot, double-blind, placebo-controlled trials.
Edwards KR, Potter DL, Wu SC, Kamin M, Hulihan J.
Department of Neurology, Harvard Medical School School and Beth Israel Deaconess Medical Center in Boston, Massachusetts, USA.
kedwards@vtneuro.com.
The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6-8 week titration, and 8-12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.

Curr Pain Headache Rep. 2003 Feb;7(1):63-6. : 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.com
The 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.

Characteristics and indications of topiramate
AIM. To evaluate the efficiency of topiramate (TPM), an antiepileptic medication (AEM) which possesses multiple mechanisms of action and good pharmacokinetics, in the different types of childhood epilepsy and to make an appraisal of its value in migraines, bipolar disorder, eating disorders and neuropathic pain, according to studies that have been published. To do so, we have made use of an analysis of the literature, together with a multi centre study conducted in Spain and personal casuistry. METHOD. We consider the percentage of seizure free patients and of patients who responded (reduction of 50% or above in the frequency of the seizures) in childhood epilepsy, partial epilepsy, generalized tonic clonic seizures, absence seizures, tonic seizures, patients with diverse types of seizures, juvenile myoclonic epilepsy, Lennox Gastaut syndrome, falling sickness and GTCS, West s syndrome and Dravet s syndrome. With monotherapy, in partial epilepsy, between 39 and 54% of patients treated were seizure free. TPM has also proved to be efficient in experiments with animals, as a neuroprotector, and in clinical trials, in type I bipolar disorder, eating disorders, neuropathic pain and migraine. CONCLUSIONS. TPM is an AEM offering a wide therapeutic spectrum that has proved to be efficient in clinical trials, expansion phases and observational studies, as an associated drug in partial epilepsy, generalized epilepsy, Lennox Gastaut syndrome, West s syndrome and Dravet s syndrome. It has proved to be more efficient in monotherapy, in partial epilepsy, as a first line AEM. TPM has also proved to be useful in mood disorders, eating disorders, neuropathic pain and tremor in observational studies, although this efficiency has not been backed up by clinical trials. In migraine and in clinical trials TPM has shown its efficiency. Its neuroprotective effect opens up new therapeutic perspectives.

Headache 2002 Nov-Dec;42(10):978-83 : Cost-effectiveness of antiepileptic drugs in migraine prophylaxis.
Adelman JU, Adelman LC, Von Seggern R.
Headache Wellness Center, Greensboro, North Carolina.
Objective.-To analyze the cost-effectiveness of antiepileptics in migraine prophylaxis. Methods.-A cost-effectiveness analysis was performed using efficacy data from three recent, double-blind, placebo-controlled, clinical trials of antiepileptic drugs studied for migraine prevention and cost data. Two measures of cost-effectiveness were used: cost per headache prevented and the cost-equivalent number. Results.-In the double-blind, placebo-controlled, clinical trials evaluated, three antiepileptic drugs were shown to be effective in migraine prevention. All three antiepileptic drugs had high costs per migraine reduced. Gabapentin was the most costly at $138.00 per migraine prevented, whereas the cost per migraine prevented with topiramate was $114.80 and with divalproex sodium was $48.00. For migraine prevention divalproex sodium became cost-effective with 10 migraines per month, whereas gabapentin and topiramate required considerably more migraines per month to be cost-effective. Conclusions.-Antiepileptic drugs have proven effectiveness in migraine prophylaxis. However, in patients responsive to their acute care medications, the antiepileptic drugs are only cost-effective for those patients with a high frequency of migraines and those with comorbid diseases. Future studies should be done with antiepileptic drugs in patients exhibiting a migraine frequency of 10 or more headaches per month.

Surv Ophthalmol. 2003 Jul-Aug;48(4):447-51. : Foggy visual field defect.
Foroozan R, Buono LM.
Neuro-Ophthalmology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
A 32-year-old female migraneur developed a right incongruous homonymous hemianopia after taking the antiepileptic agent, topiramate. The visual field defect partially resolved when the medication was discontinued. The differential diagnosis of the homonymous hemianopia is discussed.

Curr Opin Neurol. 2003 Jun;16(3):341-5. : The evolving management of migraine.
Ashkenazi A, Silberstein SD.
Jefferson Headache Center, Department of Neurology, Thomas Jefferson University Hospital, Gibbon Building, Suite #8130, 111 South Eleventh Street, Philadelphia, PA 19107, USA.
PURPOSE OF REVIEW: To review recent advances in acute and preventive migraine treatment. RECENT FINDINGS: The number of migraine drugs continues to expand, allowing for more flexible and tolerable treatment plans. Two new triptans, frovatriptan and eletriptan, and a nasal formulation of zolmitriptan have been recently developed. Eletriptan is effective for acute migraine treatment and may have some pharmacologic and clinical advantages. Frovatriptan has a longer half-life and lower headache recurrence rates compared with other triptans. It may be useful for patients who have prolonged attacks and high headache recurrence rate. Zolmitriptan nasal spray has a rapid onset of action and high efficacy. It should be considered when patients have rapid-onset attacks, especially when associated with severe nausea or vomiting. The butyrophenone neuroleptic droperidol is very effective in aborting acute migraine attacks. Central nervous system side effects are common, however, and the ECG should be monitored. Botulinum toxin type A shows promise as a safe, tolerable and effective drug for migraine prevention, with the unique advantages of almost no systemic adverse events and a long interval between treatments. The anticonvulsant topiramate is effective for migraine prevention. Cognitive side effects are of less concern with the lower doses needed for migraine. The angiotensin converting enzyme receptor blocker candesartan appears to be effective and highly tolerable in the prevention of migraine, but needs to be further evaluated. SUMMARY: New drugs expand the spectrum of migraine treatment both for the acute attack and for prevention. Curr Pain Headache Rep. 2003 Feb;7(1):63-6.: 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.com
The 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.

Headache 2001 Nov-Dec;41 Suppl 1:S18-24 : Antiepileptic drugs in migraine prevention.
Mathew NT.
University of Texas Medical School and Houston Headache Clinic, Houston, TX 77004, USA.
Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including beta-blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P< or =.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P =.09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P =.0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P =.0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention.

New and emerging prophylactic agents for migraine.
Frequent, severe and long-lasting migraine attacks require prophylaxis. Established drugs used for the prevention of migraine such as beta-adrenoceptor antagonists (beta-blockers), calcium channel antagonists, antidepressants and others have an unknown mode of action in migraine. Their prophylactic effect in migraine was discovered by chance in clinical practice when these drugs were used for other purposes. Recently, research into the mechanisms of migraine and the progressive recognition that cortical hyperexcitability and an imbalance between neuronal inhibition [mediated by gamma-aminobutyric acid (GABA)] and excitation (mediated by excitatory amino acids) may play an important role in migraine pathophysiology have lead to the identification of potential new agents for the prevention of migraine attacks. This paper reviews the recent literature on these new agents. A search was conducted using MEDLINE from 1998 to November 2001 with the following search terms: migraine, preventive, prophylactic and treatment. Headache textbooks edited in 2000 and 2001 were also used. After analysing the available controlled and uncontrolled clinical studies as well as abstracts, divalproex sodium (valproate semisodium) can be recommended for the prevention of migraine. Lamotrigine may be useful for preventing aura associated with migraine, and topiramate seems a promising option pending trials with more patients, which are currently underway. Riboflavin (which is possibly involved in improving neuronal energy production) appears to be a promising agent, although comparisons with established prophylactic medications are needed. Gabapentin, magnesium, lisinopril and botulinum toxin A have recently been suggested to be effective; however, at present, there are insufficient rigorous and reliable controlled data on these drugs for them to be indicated for such use. Emerging options such as tiagabine, levetiracetam, zonisamide and petasites may all be useful, but controlled data are required to confirm their efficacy. The anti-asthma medication montelukast was found to be effective in an open trial, but ineffective in a recently completed controlled trial. There is an expectation that modern neuroscience will soon provide more efficacious and better tolerated prophylactic medications for migraine.

Topiramate in migraine prevention: a double-blind, placebo-controlled study.
OBJECTIVE: To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine. BACKGROUND: Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine. METHODS: Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase. RESULTS: During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment. CONCLUSIONS: Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.

Antiepileptic drugs: how they work in headache.
Antiepileptic drugs (AEDs) are promising agents for the prevention of migraine and other head pain. Migraine and epilepsy share several clinical features and respond to many of the same pharmacologic agents, suggesting that similar mechanisms may be involved in their pathophysiology. The mechanisms of action of AEDs are not fully understood, and a single drug may have more than one mechanism, both in epilepsy and in migraine. Valproate, topiramate, and gabapentin are likely to affect nociception by modulating gamma-aminobutyric acid- (GABA-) and/or glutamate-mediated neurotransmission. All three AEDs enhance GABA-mediated inhibition. Valproate and gabapentin interfere with GABA metabolism to prevent its ultimate conversion to succinate, and topiramate potentiates GABA-mediated inhibition by facilitating the action of GABA receptors. In addition, topiramate acts directly on non-N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate glutamate receptors. Valproate, topiramate, and possibly gabapentin inhibit sodium ion channels. All three drugs modulate calcium ion channel activity. Valproate blocks T-type calcium ion channels; topiramate inhibits high-voltage-activated L-type calcium ion channels; and gabapentin binds to the alpha2delta subunit of L-type calcium ion channels. AEDs may be useful in migraine prevention through such mechanisms as modulating the biochemical phenomena of aura or acting directly on the nociceptive system. Further evaluations of AEDs in migraine models will provide a better understanding of the pathophysiology and prevention of migraine.

Antiepileptic drugs in migraine prevention.
Migraineurs may continue to experience attacks, despite daily use of one or more agents from a wide range of drugs, including beta-blockers, calcium channel blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic drug approved for migraine prevention. Gabapentin, topiramate, and other antiepileptic agents are being evaluated for migraine prevention and treatment. Prospective, double-blind, placebo-controlled clinical trials of divalproex, gabapentin, and topiramate for migraine prevention generally were composed of a prospective baseline period, a dose titration period, and a fixed-dose treatment period. The primary efficacy variable was a reduction in the 28-day frequency of migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500 mg/day achieved significant decreases in the migraine frequency (P<.05), corresponding to reductions of 30% to 40% compared with baseline. Nearly half of the divalproex-treated patients had a 50% or more reduction from baseline in headache frequencies (P< or =.05). Asthenia, vomiting, somnolence, tremor, and alopecia were common adverse events associated with divalproex. Significant reductions in migraine frequency were also observed with gabapentin (1800 to 2400 mg/day) when compared with placebo (P<.01), and nearly half of all patients treated at the highest dose experienced a reduction in headache rate of 50% or more. Somnolence was the most commonly reported adverse event among the gabapentin-treated patients. Two single-center, double-blind, placebo-controlled clinical trials evaluated topiramate for migraine prevention. A lower 28-day migraine frequency was seen during 18 weeks of administration at a maximum daily dose of 200 mg (P =.09). In a second study, a significantly lower mean 28-day migraine frequency was observed during 16 weeks of treatment with topiramate (P =.0015). Mean reduction in migraine frequency was also significantly greater in topiramate-treated patients (P =.0037). Paresthesias, diarrhea, somnolence, and altered taste were commonly reported adverse events in the topiramate-treated patients. Unlike some patients given divalproex or gabapentin, some given topiramate reported weight loss. Large, double-blind, placebo-controlled trials may prove the effectiveness of novel antiepileptic drugs in migraine prevention.

drugs that might help in migraine preventation-A MUST READ...JUST TIP OF ICEBERG AS TO WHAT IT CONTAINS

Leukotriene-Antagonists-They include zileuton (Ziflo), zafirlukast (Accolate), montelukast (Singulair), and pranlukast (Ultair, Onon).

Angiotensin Converting Enzyme (ACE) Inhibitors. Commonly used for treating high blood pressure, ACE
ielisinopril

Hormone Replacement TherapyORAL CONCEPTIVES

Positive Effects. Oral contraceptives, however, appear to help about 35% of women with migraines.

Negative Effects. Oral contraceptives have been associated with worse headaches in 18% to 50% of women and have also been linked to a higher risk for stroke in women with migraines.

Ergots-Ergotamine and dihydroergotamine (DHE)

CALCIUM BLOCKERS-Verapamildiltiazem (Cardizem), nimodipine (Nimotop), nifedipine (Procardia), amlodipine (Norvasc), felodipine (Plendil), and nisoldipine (Sular).

Antidepressants-Tricyclic antidepressants. They include amitriptyline (Elavil, Endep) and protriptyline (Vivactil).MMThe selective serotonin-reuptake inhibitors (SSRIs) and similar agents. These include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox). Nefazodone (Serzone

Anticonvulsants-Valproate and Divalproex Sodium.. gabapentin (Neurontin), topiramate (Topamax), and tiagabine (Gabitril).

bETA bLOCKERS-Propranolol (Inderal) and timolol (Blocadren) have been approved specifically for prevention of migraine. offlabel-tenolol (Tenormin), metoprolol (Lopressor, Toprol XL), and nadolol (Corgard).