Valproate and lamotrigine in migraine.
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Calcium Channel Blockers↗
Biomedical subjects
N T Mathew
Publications and source records attributed to N T Mathew.
Ineffectiveness of neurokinin-1 antagonist in acute migraine: a crossover study.
Lanepitant is a high-affinity, selective neurokinin-1 receptor (NK-1) and is effective in the dural inflammation model of acute migraine. Lanepitant 30, 80, and 240 mg given orally was evaluated in a double-blind, placebo-controlled crossover study to determine its effect in reducing migraine pain and severity of associated symptoms. Outpatients treated four migraine headaches of moderate or severe pain intensity with study drug according to a randomization schedule. They recorded their pain intensity and severity of migraine-associated symptoms at 30, 60, 90, and 120 min. Although 53 patients were randomly allocated to a treatment sequence, only 40 patients completed all treatments. There was no statistically significant difference in improvement in migraine pain at any time for any of the treatments. Additionally, there was no change in severity of migraine-associated symptoms associated with lanepitant therapy. No adverse events could be attributed to lanepitant. Lanepitant was ineffective orally in treating acute migraine in this trial. This may be due to poor bioavailability during a migraine attack. Alternatively, the neurogenic inflammation hypothesis may not apply to migraine.
Acute Disease↗
Cluster headache.
Cluster headache is characterized by regular periodicity, high frequency during a cluster period, relative brevity, and extreme intensity. Lancinations, as in trigeminal neuralgia, are rare. An important behavioral difference between migraine and cluster headache is that the patient is usually hyperactive during a cluster headache, whereas the migraineur retreats to a dark, quiet room. Cluster headache is more common in middle-aged men; migraine is more common in young women. Intermediate or overlap syndromes occur. Many of the same prophylactic and abortive treatments are effective in both, although in cluster headache there is a premium on rapid action.
Acute Disease↗
Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. The 017 Clinical Trial Study Group.
This study investigated the efficacy of zolmitriptan (Zomig, formerly 311C90) in acute migraine therapy. Patients with a history of migraine were randomized in a double-blind, multicenter, placebo-controlled, dose range-finding study of oral zolmitriptan 1, 2.5, 5, or 10 mg versus placebo for the treatment of a severe or moderate migraine headache. Patients with persistent or recurrent headache 4 to 24 hours after the initial dose, who did not take escape medication, were eligible to receive a second blinded dose of either zolmitriptan or placebo. Of 1,144 patients treated, 999 evaluable patients completed the study. The headache response rates with zolmitriptan doses > or = 2.5 mg were 44 to 51% at 1 hour, 65 to 67% at 2 hours, and 75 to 78% at 4 hours (all significantly superior to placebo). Also, zolmitriptan effectively relieved migraine-associated symptoms such as nausea, photophobia and phonophobia, and reduced activity impairment. Rates of headache recurrence, headache persistence, and use of escape medication were lower with zolmitriptan doses > or = 2.5 mg than with placebo. In patients with persistent or recurrent headache, a second zolmitriptan dose effectively treated both headache and nonheadache symptoms. Zolmitriptan was well tolerated, with a lower incidence of adverse events being reported with doses < or = 2.5 mg than with those > or = 5 mg. Zolmitriptan is a well tolerated and effective acute migraine therapy providing rapid relief of migraine headache within 1 hour. A clear dose-response relationship between efficacy and tolerability suggests that 2.5 mg is the optimal initial dose for the acute treatment of a migraine attack.
Acute Disease↗
Naratriptan is effective and well tolerated in the acute treatment of migraine. Results of a double-blind, placebo-controlled, crossover study. The Naratriptan S2WA3003 Study Group.
The efficacy and tolerability of naratriptan tablets (2.5 mg, 1 mg, and 0.25 mg) compared with placebo in the acute treatment of migraine were evaluated in a randomized, double-blind, four-period crossover study. Five hundred eighty-six assessable patients received naratriptan 2.5 mg, 595 received 1 mg, 591 received 0.25 mg, 602 received placebo. Headache relief (moderate or severe pain reduced to mild or none) 4 hours postdose was reported in 68% of patients after treatment with naratriptan 2.5 mg compared with 57% after 1 mg, 39% after 0.25 mg, and 33% after placebo (p < 0.001 naratriptan 2.5 mg and 1 mg versus placebo and 1 mg and 2.5 mg versus 0.25 mg). Headache relief was maintained 8, 12, and 24 hours postdose with no use of rescue medication or a second dose of study medication by significantly (p < 0.001) greater percentages of patients after treatment with naratriptan 2.5 mg or 1 mg compared with naratriptan 0.25 mg or placebo. Naratriptan was also more effective than placebo in reducing clinical disability and the incidences of nausea, photophobia, and phonophobia. The overall incidence of adverse events and the incidences of specific adverse events did not differ in the naratriptan groups compared with placebo. No clinically relevant changes in ECG, blood pressure, or laboratory findings were reported. These data demonstrate that naratriptan is effective and well tolerated for the acute treatment of migraine. The 2.5-mg dose was associated with superior efficacy, whereas its adverse event profile was similar to that of placebo.
Adolescent↗
Dosing and administration of ergotamine tartrate and dihydroergotamine.
Ergotamine tartrate (ET) and dihydroergotamine (DHE) are effective therapies for migraine and cluster headache. Optimal management with these agents must take several factors into account, including headache type and severity, associated symptoms, side effect potential, choice of dosage forms, and appropriate dosing. Oral ET is most appropriate for slowly evolving migraine without early onset nausea and/or vomiting, or for treatment of cluster headaches. Delivery of ET via rectal suppository (available only in combination with caffeine) is the most effective form, especially for patients with severe, rapid onset migraine accompanied by nausea and/or vomiting. Dihydroergotamine offers numerous benefits compared to ET, including a lower incidence of nausea and vomiting and headache recurrence, and a lack of rebound headache. Dihydroergotamine can be administered at any time during a migraine attack, including the aura. Intravenous administration provides rapid peak plasma levels and is the most effective form when a rapid effect is desired or for patients with intractable severe headache (status migrainosus, transformed migraine, rebound headache) and cluster headache. Intramuscular administration is effective for moderate to severe migraine with or without nausea and vomiting in the clinic. Intranasal delivery of DHE has shown significant promise for effective and convenient therapy in acute migraine and may be especially useful in the presence of nausea and/or vomiting. When used appropriately, DHE and ET provide clinicians with highly effective therapeutic options in a range of useful dosage forms for patients with migraine or cluster headaches.
Analgesics, Non-Narcotic↗
Serotonin syndrome complicating migraine pharmacotherapy.
Serotonin syndrome, a condition with numerous clinical neurological manifestations, is the result of central serotonergic hyperstimulation. Features of the syndrome include mental status and behavioral changes (agitation, excitement, hypomania, obtundation), motor system involvement (myoclonus, hemiballismus, tremor, hyperreflexia, motor weakness, dysarthria, ataxia) and autonomic symptoms (fever, chills, diarrhea). Serotonin syndrome has been reported exclusively in patients on medications for psychiatric illness and Parkinsonism, despite the fact that the putative action of many antimigraine agents also involves the serotonin system. We herein report six patients with migraine who developed symptoms suggestive of the serotonin syndrome. Five were taking one or more serotomimetic agents for migraine prophylaxis (sertraline, paroxetine, lithium, imipramine, amitriptyline). In each case the symptoms and signs developed in close temporal proximity with use of a migraine abortive agent known to interact with serotonin receptors. In three instances the agent was subcutaneous sumatriptan and, in three, intravenous dihydroergotamine. In each instance the symptoms were transient and there was full recovery. With the ever increasing use of migraine medications active at serotonin receptor sites, cases of serotonin syndrome will likely occur more frequently. It is important that physicians treating migraine are aware of the serotonin syndrome and are able to recognize its varying presentations.
Adult↗
Coexistence of migraine and idiopathic intracranial hypertension without papilledema.
Eighty-five patients with refractory transformed migraine type of chronic daily headache (CDH) had spinal tap as a part of diagnostic work-up. Twelve had increased intracranial pressure without papilledema, transient visual obscurations, or visual field defects. The headache profile of these 12 patients was not different from that of transformed migraine type of CDH. Acute headache exacerbations responded to specific antimigraine agents such as ergotamine, dihydroergotamine (DHE), and sumatriptan, whereas prophylactic antimigraine medications were only partially helpful. Addition of agents such as acetazolamide and furosemide, after the diagnosis of increased intracranial pressure, resulted in better control of symptoms. These observations suggest a link between migraine and idiopathic intracranial hypertension that needs further research. In refractory CDH with migrainous features, a spinal tap to exclude coexistent idiopathic intracranial hypertension without papilledema may be indicated.
Acetazolamide↗
Migraine prophylaxis with divalproex.
OBJECTIVE: To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache. DESIGN: Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance). SETTING: Eight headache/neurology clinics throughout the United States. PATIENTS: One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo. INTERVENTION: Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L. MEASUREMENTS AND MAIN RESULTS: During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group (p < or = .001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase (P < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant). CONCLUSIONS: Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.
Adolescent↗
Long-term subcutaneous sumatriptan in cluster headache.
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Clinical Trials as Topic↗
The International Headache Society (IHS) headache classification as applied to a headache clinic population.
Four hundred patients attending a headache clinic were classified using the IHS criteria. The majority required more than two, often three or four, diagnoses. Even though migraine was the most common diagnosis, only 1/4 of those with a migraine diagnosis had it as the only diagnosis. Seventy-five percent of migraine patients had coexistent chronic tension-type headache (CTTH), drug-induced headache or both. Ninety-six percent of patients diagnosed as having migraine with aura also suffered from migraine without aura. More than 1/3 of patients (37.7%) attending the clinic suffered from chronic daily headache (CDH) (chronic cluster headache excluded), which is not included as a separate entity in the IHS classification. Pure CTTH formed only a small minority of CDH, whereas 86.6% of CDH had migraine as one of the diagnoses. Drug-induced headache was a prominent second or third diagnosis. The advantages and disadvantages of multiple verses single diagnosis in CDH and the need to recognize the natural history of headache disorders in the classification are discussed.
Ambulatory Care Facilities↗
Classification of daily and near-daily headaches: proposed revisions to the IHS criteria.
The International Headache Society (IHS) headache classification, while a major advance, does not adequately classify the daily and near-daily headache disorders known as chronic daily headache (CDH). We believe that chronic daily headache is a group of disorders which includes chronic tension-type headache (CTTH), transformed migraine (TM), new daily persistent headache (NDPH), and hemicrania continua (HC). We propose specific criteria for transformed migraine, new daily persistent headache, and hemicrania continua, and have modified the criteria for chronic tension-type headache.
Chronic Disease↗
Valproate in intractable headache.
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Brain↗
Severe diffuse intracranial vasospasm as a cause of extensive migrainous cerebral infarction.
We report on a 47-year-old white female with a long history of recurrent episodes of migraine with aura, who progressed to develop a continuous intractable headache during the course of which cortical blindness and quadriparesis occurred due to extensive and bilateral hemispheric cerebral infarction. Severe diffuse intracranial major arterial vasospasm was demonstrated by arteriogram. All studies were negative for CNS vasculitis, including cerebral biopsy. The arterial spasm reversed itself, but the patient did not improve. Smoking was the only additional risk factor. Vasospasm is an important cause to be considered in migrainous infarctions. The use of vasoconstrictor agents such as DHE in patients with migraine with prolonged aura has to be carefully re-evaluated.
Blindness↗
Transformed migraine.
Chronic tension-type headache, which is included in the International Headache Classification, is present in only a minority of patients who present with chronic daily headache. The majority have what is termed transformed migraine, with a history of distinct episodes of migraine in the initial years which progresses into chronic daily headache. These patients with transformed migraine exhibit mixed features of migraine and chronic tension-type headache. Two distinct types of transformed migraine are identifiable, namely those related to excessive intake of medications (drug-induced transformed migraine) and those unrelated to excessive use of medications. The clinical features of transformed migraine and the drug-induced variety are described. The need for revision of the International Classification to include chronic daily headache and the subtypes of transformed migraine is pointed out.
Adult↗
Chronic refractory headache.
Approximately 40% of patients seen in major headache clinics suffer from chronic daily headache. Of a series of 630 patients with chronic daily headache, 489 were diagnosed with transformed migraine, 84 with chronic tension-type headache, and 57 with new daily persistent headache. Of these patients, 73% overused symptomatic medication, particularly analgesics and ergotamine, and as a result, suffered from drug-induced headache or rebound headache.
Adult↗
Dose ranging efficacy and safety of subcutaneous sumatriptan in the acute treatment of migraine. US Sumatriptan Research Group.
Sumatriptan, a specific serotonin1-like receptor agonist, was studied in the acute treatment of migraine. Two hundred forty-two adult migraineurs participated in a randomized, double-blind study in which one dose of 1, 2, 3, 4, 6, or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion. At each dose level, a placebo group was included. Efficacy was defined as reduction of moderate or severe pain to mild or no pain, without the use of rescue medication. Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. Relief of nausea and improvement in clinical disability were also approximately dose related. Adverse events were dose related; the most common types were injection site reactions and tingling. The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal.
Adult↗
Valproate in the prophylaxis of migraine.
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Humans↗