Low-dose topiramate versus lamotrigine in migraine prophylaxis (the Lotolamp study). Effects of levetiracetam vs topiramate and placebo on visually evoked phase synchronization changes of alpha rhythm in migraine. Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. Oxcarbazepine in migraine headache: a double-blind, randomized, placebo-controlled study. Zonisamide versus topiramate in migraine prophylaxis: a double-blind randomized clinical trial. Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised placebo-controlled trial. Evaluation of carisbamate for the treatment of migraine in a randomized, double-blind trial. Aetiology of migraine and prevention with carbamazepine (Tegretol): results of a double-blind, cross-over study. Clonazepam (rivotril) in migraine prophylaxis.
To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo.
                Sixty patients with frequent migraine (more than 4 attacks per month) from the headache clinic at a tertiary referral centre in India were randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between. Primary efficacy measure was responder rate (50% decrease in mean migraine frequency/intensity). Secondary efficacy measures included reduction in mean monthly frequency, intensity, duration, rescue medication use, migraine associated symptoms, and adverse events.
                Analysis was on intention to treat basis. Data were analyzed as correlated data. Generalized estimation equation was used to compute overall mean standard deviation and 95% confidence intervals for each of the outcome variables. Bonferroni's correction done for multiple comparisons. P value of < .017 was taken as significant.
                Fifty-seven patients comprised the intent-to-treat population. Four patients withdrew from the study at various phases, none because of the side effects. Responder rate for frequency was significantly higher for topiramate versus placebo (63% vs 30%, P < .001), and versus lamotrigine (63% vs 46 %, P = .02). For intensity of headache also a responder rate of topiramate versus placebo (50% vs 10%, P < .001), and versus lamotrigine (50% vs 41%, P = .01) was observed. Topiramate showed statistically significant benefits (P < .017) in most of the secondary efficacy measures while lamotrigine was beneficial for reduction in headache frequency, and migraine associated symptoms. Adverse events were similar.
                Low-dose topiramate is efficacious in migraine prophylaxis as compared to both placebo and lamotrigine. Lamotrigine in low doses might be beneficial for headache frequency; however, longer trials are required to establish its efficacy on the intensity and frequency of migraine. Recent theories about migraine pathogenesis have outlined an abnormal central processing of sensory signals, also suggested by an abnormal pattern of EEG hyper-synchronization under visual stimulation. The aim of the present study was to test the efficacy of topiramate and levetiracetam vs placebo in a double blind project observing the effects of the three treatments on the EEG synchronization in the alpha band under sustained flash stimulation.
                Forty-five migraine without aura outpatients (MO) were selected and randomly assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In addition, 24 non-migraine healthy controls were submitted to EEG analysis. The EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase synchronization index, that we previously applied in migraine, after EEG signals filtering in the alpha band. Our approach was based on the Hilbert transform.
                Both levetiracetam and topiramate significantly decreased migraine frequency, compared with placebo. MO patients displayed increased alpha-band phase synchronization as an effect of stimulus frequency; on the other hand the stimuli had an overall desynchronizing effect on control subjects. The phase synchronization index separates the two stages, before and after the treatment, only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz.
                An abnormal alpha band synchronization under visual stimuli was confirmed in migraine; this phenomenon was reversed by levetiracetam preventive treatment.
                These results confirmed in humans the inhibiting action of levetiracetam on neuronal hyper-synchronization. Lamotrigine blocks voltage-sensitive sodium channels, leading to inhibition of neuronal release of glutamate. Release of glutamate may be essential in the propagation of spreading cortical depression, which some believe is central to the genesis of migraine attacks. This study compared safety and efficacy of lamotrigine and placebo in migraine prophylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo-responders and non-compliers were excluded, leaving 77 to be treated with lamotrigine (n = 37) or placebo (n = 40) for up to 3 months. Initially, lamotrigine therapy was commenced at the full dose of 200 mg/day, but, following a high incidence of skin rashes, a slow dose-escalation was introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on lamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that lamotrigine is ineffective for migraine prophylaxis. There were more adverse events on lamotrigine than on placebo, most commonly rash. With slow dose-escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups. To evaluate the efficacy, safety, and tolerability of oxcarbazepine (1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine headaches.
                This multicenter, double-blind, randomized, placebo-controlled, parallel-group trial consisted of a 4-week single-blind baseline phase and a 15-week double-blind phase consisting of a 6-week titration period, an 8-week maintenance period, and a 1-week down-titration period, after which patients could enter a 13-week open-label extension phase. During the 6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The primary outcome measure was change from baseline in the number of migraine attacks during the last 28-day period of the double-blind phase.
                Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive placebo. There was no difference between the oxcarbazepine (-1.30) and placebo groups in mean change in number of migraine attacks from baseline during the last 28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients (65%). The majority of adverse events were mild or moderate in severity. The most common adverse events (>or=15% of patients) in the oxcarbazepine-treated group were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event occurred in more than 15% of the placebo-treated patients.
                Overall, oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show efficacy in the prophylactic treatment of migraine headaches. Topiramate is an antiepileptic drug that has been approved for migraine prophylaxis. Despite appropriate efficacy for migraine prophylaxis, some patients cannot tolerate its adverse effects. The aim of this study was to compare the efficacy of zonisamide, another antiepileptic drug, with topiramate in decreasing the frequency and severity of migraine attacks to determine whether it could be used as an alternative for noncompliant patients to topiramate.
                Eighty patients, recruited from referred migraineurs to our neurology clinic, who met the diagnosis and inclusion criteria were allocated randomly to group A (50-mg/d zonisamide, gradually titrated up to 200 mg/d) and group B (25-mg/d topiramate, gradually titrated up to 100 mg/d). Each patient was followed for 12 weeks and was assessed at entrance, in the fourth week and twelfth week for frequency of attacks, headache severity, need for acute medication, migraine disability assessment score, and adverse effects. A P < 0.05 was considered as the level of significant difference in all tests.
                Both drugs caused a significant decrease in frequency, severity, need for acute medication in migraine attacks, and migraine disability assessment score (P < 0.05). Except headache severity that was reduced significantly better by zonisamide (P < 0.008), there were no significant difference between the 2 groups in other items. Except for 2 cases of intolerable paresthesia, both drugs were tolerated well during the study.
                Our results indicated that zonisamide is as effective as topiramate in migraine prophylaxis and can be considered as an alternative treatment when topiramate is not tolerated well. Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are allelic disorders with distinct types of mutations in the CACNA1A gene. EA2 attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.
                To evaluate the efficacy and the tolerability of acetazolamide in migraine prophylaxis.
                We compared daily oral 500 mg acetazolamide and placebo in patients with migraine in a multicentre, double-blind, randomised trial of 12 weeks duration after a run-in period of 4 weeks without treatment. Frequency of attacks at the last trial period of 4 weeks was the primary efficacy criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks, the severity and duration of attacks, the number of hours with migraine as well as the number of responders with more than 50% reduction in attack frequency.
                53 patients had been enrolled when the study was prematurely stopped because of a high number of withdrawals (34%), primarily linked to acetazolamide related side effects. Considering the primary and secondary efficacy criteria, among the 53 included patients (27 in the placebo group and 26 in the acetazolamide group), no difference between the 2 study groups could be demonstrated. The most frequent adverse events related to acetazolamide were paresthesias and asthenia.
                In this trial, migraine sufferers poorly tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious prophylactic beneficial effect of acetazolamide appeared on migraine attacks. This study explored the dose-response relationship of carisbamate administered at doses of 100 mg per day, 300 mg per day, or 600 mg per day, in the prevention of migraine.
                Carisbamate ([S]-2-O-carbamoyl-1-o-chlorophenyl-ethanol; RWJ 333369) is a new chemical entity being studied for efficacy as adjunctive therapy in partial onset epilepsy. Because some antiepileptic drugs are also efficacious in migraine, for example, topiramate and valproate sodium, we tested carisbamate in migraine prophylaxis.
                This was a double-blind, placebo-controlled trial, approximately 22-week duration. The primary efficacy variable was the percent reduction from baseline through the double-blind phase in average monthly migraine frequency using a 48-hour rule. Patients were randomized 1 : 1 : 1 : 1 to treatment with carisbamate 100, 300, or 600 mg per day, or placebo. Migraine attacks were counted during a prospective 4-week baseline period, which was followed by a 2-week titration period, a 12-week maintenance period, a 1-week medication reduction period, and a 3-week observation period. Patients had an established history of migraine, with or without aura, for at least 1 year and a 3-month history of 3-12 migraine attacks per month.
                Patients (n = 323) were predominantly women (85%) and white (89%); mean age was 41 years. There were no statistically significant differences between any of the carisbamate groups and placebo (P > or = .6) for the median (range) percentage reduction from baseline to end point in average monthly migraine frequency (P value vs placebo): 37% (-250%, 100%) for placebo; 33% (-210%, 100%; P = .7) CRS 100 mg/day; 27% (-100%, 100%; P = .8) CRS 300 mg/day; and 35% (-87%, 100%; P = .6) CRS 600 mg/day. Results for secondary efficacy measures (responder rate, percent reduction in average monthly migraine frequency using the 24-hour rule, and percent reduction in average monthly migraine days) were consistent (P > or = .075). The proportion of patients discontinuing because of adverse events was similar for placebo and carisbamate-treated patients (13% each). The most common (occurring in > or =5% of patients) treatment-emergent adverse events in patients treated with carisbamate were fatigue (17%) and nasopharyngitis (13%). Fatigue appeared to be dose related.
                Carisbamate was not more efficacious in migraine prophylaxis than placebo in this well-controlled study that included a suitable population. However, carisbamate monotherapy was well tolerated at doses up to 600 mg per day. nan nan
Available evidence does not allow robust conclusions regarding the efficacy of antiepileptic drugs other than gabapentin, pregabalin, topiramate, and valproate in the prophylaxis of episodic migraine among adults. Acetazolamide, carisbamate, clonazepam, lamotrigine, oxcarbazepine, and vigabatrin were not more effective than placebo in reducing headache frequency. In one trial each, carbamazepine and levetiracetam were significantly superior to placebo in reducing headache frequency, and there was no significant difference in proportion of responders between zonisamide and active comparator. These three positive studies suffer from considerable methodological limitations.