Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1988, the first report on valproate in migraine prophylaxis was published. Since 1992, 359 patients have been investigated in five double blind studies. Valproic acid was effective in all studies compared to placebo; one study confirmed an effect similar to propranolol. There are no analyses of efficacy in comparison to plasma levels. Adverse events seem to occur somewhat more frequently than in propranolol, but are well known in epilepsy therapy. In the international literature and according to the recommendations of the German Headache Society, valproic acid is a well-established second-choice drug in migraine prophylaxis.
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PMID:[Valproic acid in prophylactic treatment of migraine]. 983 84

We report the successful use of valproate in a 44-year-old woman with migraine induced by selective serotonin reuptake inhibitors. Valproate should be considered for those patients who develop serious migraine for the first time, or worsening of previous migraine, after the initiation of treatment with selective serotonin reuptake inhibitors and for whom continued treatment with this class of drugs is important.
Headache 2000 Mar
PMID:Valproate prophylaxis for migraine induced by selective serotonin reuptake inhibitors. 1075 29

The authors presented the results of treatment with lamotrigine (LTG, Lamictal) in 13 patients with drug resistant epilepsy (add-on therapy). There were 8f, 5m. aged 16-60 years, mean age 28.8 years. Generalized seizures occurred in 8 patients (62%). In this group there was 1 patient (aged 16 years) with the Lennox-Gastaut syndrome and 1 patient (aged 20 years) with valproate resistant juvenile myoclonic epilepsy. Complex partial seizures and complex partial with secondary generalization occurred in 5 patients (38%). Before LTG addition mean seizure frequency was from 3/month to several times/day. The mean duration of epilepsy was 16.6 years. The 8 patients were treated with CBZ and VPA, one with PHT and VPA, one CBZ and VGB. Monotherapy with VPA was introduced in 3 patients. After 6 months of treatment with LTG the efficacy was evaluated. 12 patients took LTG with VPA, 1 LTG with CBZ. Complete reduction of seizures was achieved in 3 cases (23%), at least 50% reduction in 3 patients (23%), reduction below 50% in 4 patients (31%). In 3 cases (23%) the results of treatment were negative (increase or no change in seizure frequency). Beneficial psychotropic effect was observed in 9 patients (69%). Adverse effects occurred in 2 patients (15%). Headache, vertigo, sleepness were observed in one case. Rash occurred in 1 patient (treated with LTG and VPA). After 6 months 3 patients were excluded from the study because of negative effects of treatment. LTG is helpful and well tolerated in drug-resistant epilepsy.
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PMID:[Lamotrigine in add-on therapy: assessment of efficacy in drug resistant epilepsy]. 1084 3

We followed 23 patients with pediatric migraine, ranging in age from 7 to 17 years, who were treated with preventive divalproex sodium for migraine prophylaxis. Patients were evaluated for the presence or absence of comorbid psychiatric disorders or epilepsy to assess the possible differential effects of divalproex therapy. Doses ranged from 3.1 to 32.9 mg/kg/day. Seven patients had comorbid psychiatric disorders, whereas six patients had epilepsy (three rolandic, two generalized, and one indeterminate). Fifteen patients had a greater than 50% reduction in migraine; six patients became headache free. Divalproex doses used were not statistically different among the three groups. A favorable response and headache freedom were more likely in patients with migraine alone or with comorbid epilepsy, and less likely in patients with psychiatric comorbidity. Divalproex was well tolerated, and no significant side effects were reported. No notable changes were noted in behavioral problems, and patients with epilepsy were well controlled. In our cohort of patients, divalproex was most effective in patients with migraine alone or comorbid epilepsy.
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PMID:Pediatric migraine prophylaxis with divalproex. 1166 46

We examined the effect of standard migraine prophylaxis with sodium valproate on repeated measures of occipital excitability using transcranial magnetic stimulation (TMS). We predicted that, comparing pre- and post-treatment assessments, a reduction in clinical migraine parameters would be paralleled by a decrease in excitability measurements.A total of 31 migraine patients enrolled in the study, for assessment prior to and 1 month after commencement of sodium valproate prophylaxis. At each assessment, we used a standardized protocol to stimulate the occipital cortex with a 90-mm circular (coil A) and 70 mm figure-of-eight (coil B) coil. We recorded the threshold stimulation intensity at which subjects just perceived phosphenes. Subjects kept detailed records of headache parameters 1 month before and also during the study period. Valproate therapy significantly improved headache indexes, as expected. In MA subjects assessed with coil B, phosphene thresholds were significantly higher post-treatment than pre-treatment, but those for MO did not change. Modest correlations were observed in MA patients between increase in phosphene threshold and decrease in headache index. Although preliminary, the findings with coil B lend some support to the notion that effective migraine prophylaxis may be achieved through lowering cortical excitability by gamma-aminobutyric acid (GABA)-ergic intervention. Further investigation of the effect of sodium valproate or other similarly acting substances on cortical excitability in migraine is warranted.
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PMID:Visual cortex excitability in migraine before and after valproate prophylaxis: a pilot study using TMS. 1178 74

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.
Headache
PMID:Antiepileptic drugs: how they work in headache. 1190 34

Cluster headache and trigeminal neuralgia are relatively rare but debilitating neurologic conditions. Although they are clinically and diagnostically distinct from migraine, many of the same pharmacologic agents are used in their management. For many patients, the attacks are so frequent and severe that abortive therapy is often ineffective; therefore, chronic preventive therapy is necessary for adequate pain control. Cluster headache and trigeminal neuralgia have several distinguishing clinical features. Cluster headache is predominantly a male disorder; trigeminal neuralgia is more prevalent in women. Individuals with cluster headaches often develop their first attack before age 25; most patients with trigeminal neuralgia are between age 50 and 70. Cluster headaches are strongly associated with tobacco smoking and triggered by alcohol consumption; trigeminal neuralgia can be triggered by such stimuli as shaving and toothbrushing. Although the pain in both disorders is excruciating, cluster headache pain is episodic and unilateral, typically surrounds the eye, and lasts 15 to 180 minutes; the pain of trigeminal neuralgia lasts just seconds and is usually limited to the tissues overlying the maxillary and mandibular divisions of the trigeminal nerve. Cluster headache is unique because of its associated autonomic symptoms. Although the pathophysiology of cluster headache and trigeminal neuralgia are not completely understood, both appear to have central primary processes, and these findings have prompted investigations of the effectiveness of the newer antiepileptic drugs for cluster headache prevention and for the treatment of trigeminal neuralgia. The traditional antiepileptic drugs phenytoin and carbamazepine have been used for the treatment of trigeminal neuralgia for a number of years, and while they are effective, they can sometimes cause central nervous system effects such as drowsiness, ataxia, somnolence, and diplopia. Reports of studies in small numbers of patients or individual case studies indicate that the newer antiepileptic drugs are effective in providing pain relief for trigeminal neuralgia and cluster headache sufferers, with fewer central nervous system side effects. Divalproex has been shown to provide effective pain control and to reduce cluster headache frequency by more than half in episodic and chronic cluster headache sufferers. Topiramate demonstrated efficacy in a study of 15 patients, with a mean time to induction of cluster headache remission of 1.4 weeks (range, 1 day to 3 weeks). In the treatment of trigeminal neuralgia, gabapentin has been shown to be effective in an open-label study. When added to an existing but ineffective regimen of carbamazepine or phenytoin, lamotrigine provided improved pain relief; it also may work as monotherapy. Topiramate provided a sustained analgesic effect when administered to patients with trigeminal neuralgia. The newer antiepileptic drugs show considerable promise in the management of cluster headache and trigeminal neuralgia.
Headache
PMID:Antiepileptic drugs in the management of cluster headache and trigeminal neuralgia. 1190 37

Valproic acid has been used in the treatment of migraine headache for nearly 20 years. During this period of use several additional delivery modes have been developed to either improve tolerability or patient compliance with the divalproex sodium formulation and the extended-release formulation of divalproex sodium. Additionally, an intravenous formulation has become available which permits rapid achievement of therapeutic levels of the drug. There have been a number of reports on the use of valproic acid in migraine and other headache disorders, suggesting it to be an efficacious treatment. This paper reviews the results of the published reports of valproic acid in migraine and other headache disorders, including open-label studies, comparator trials, and double-blind, placebo-controlled trials. These studies have been conducted with the various formulations of valproic acid that have been on the market. The papers utilized in this study were obtained though Medline searches on valproic acid and divalproex sodium coupled with the various headache disorders. Additionally, the CD-ROM of past issues of Headache and Cephalalgia was reviewed for similar keywords. Lastly, the indices of the journal Headache Quarterly were reviewed for additional articles on valproic acid and divalproex sodium. Valproic acid in its various formulations has been demonstrated to be an efficacious and well-tolerated agent for the preventive treatment of migraine, chronic daily headache, and cluster headache. Additionally, it has been demonstrated to be efficacious and well tolerated in treating acute migraine attacks when given as an intravenous solution.
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PMID:Divalproex in the treatment of migraine. 1502 65

Migraine is a common, disabling disorder that often requires preventive treatment. The decision to treat migraine preventively generally is based on disability, problems with acute medicines, patient preference, risk of acute medication overuse, special circumstances, and concern that high migraine attack frequency may be a risk factor for chronic daily headache. Migraine and epilepsy are comorbid episodic central nervous system disorders that can have stereotyped symptoms with negative and positive phenomena. Controlled trials have demonstrated the efficacy of anticonvulsants in migraine prevention. Valproic acid, topiramate and, to a lesser extent, gabapentin, have demonstrated efficacy in randomized, placebo-controlled trials. Lamotrigine may be effective at controlling migraine aura, but has not demonstrated effectiveness at controlling migraine headache. Anticonvulsants are a useful option for the preventive treatment of migraine.
Curr Pain Headache Rep 2004 Jun
PMID:Anticonvulsants in migraine. 1511 45

Valproic acid pharmacokinetic profile and tolerability after administration of divalproex sodium extended-release tablets was characterized in older children and adolescents. In this multiple-dose, open-label, pharmacokinetic study, the patients were divided into two age groups, 8-11 years (older children; n = 15) and 12-17 years (adolescents; n = 14). Once-daily administration of divalproex sodium extended-release tablets (doses ranged from 250 to 1750 mg) in older children and adolescents produced relatively flat plasma valproic acid concentration-time profiles over the entire 24-hour dosing interval, similar to the pharmacokinetic performance of this formulation in adults. The mean (standard deviation) oral clearance values for unbound valproic acid were 94.3 (51.8) and 82.3 (28.2) mL/h/kg and for total valproic acid were 11.2 (3.77) and 9.06 (2.03) mL/h/kg in older children and adolescents, respectively. Two patients discontinued for administrative reasons, whereas one discontinued for an adverse event (flulike syndrome). Adverse events reported by three or more patients were flu syndrome (5 patients, 17.2%) and headache (3 patients, 10.3%). Reported adverse events were generally mild to moderate in severity and similar to those reported in previous divalproex studies. This study demonstrates that in older children and adolescents, once-daily administration of divalproex sodium extended-release tablets may potentially be used to sustain plasma valproic acid concentrations within the usually accepted therapeutic ranges for various indications.
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PMID:Divalproex-ER pharmacokinetics in older children and adolescents. 1516 35


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