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)

Lamotrigine (LTG) inhibits repetitive high frequency firing in depolarised neurones by selectively prolonging slow inactivation of the sodium channel, thereby suppressing the release of excitatory amino acids. It has been shown to be effective in 11 pivotal double-blind add-on trials in patients with refractory partial seizures with or without secondary generalisation. Subsequent anecdotal data support its efficacy for typical and atypical absences, myoclonic jerks, tonic or clonic seizures, Lennox-Gastaut syndrome and infantile spasms. Most recently LTG has been compared with carbamazepine and phenytoin in double-blind trials in patients with newly diagnosed partial and primary and secondary generalised tonic-clonic seizures. At the doses used, its efficacy was similar to the older agents for all seizure types, but LTG was better tolerated than both of the older agents. The commonest side-effects with LTG include headache, nausea, diplopia, dizziness, ataxia and tremor. Rash occurs in fewer than 5% patients. Its incidence can be reduced by starting treatment with a low dose, particularly in patients receiving concomitant sodium valproate which inhibits LTG metabolism. Enzyme inducers, such as carbamazepine, phenytoin and phenobarbital, accelerate its elimination, but LTG itself has no effect on hepatic metabolic processes. A pharmacodynamic interaction with carbamazepine necessitates a dosage reduction in some patients when LTG is introduced. LTG is a new antiepileptic agent with a long elimination half-life, a broad spectrum of activity, and a wide therapeutic ratio.
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PMID:Lamotrigine--an update. 895 Dec 13

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.
Cephalalgia 1997 Apr
PMID:Lamotrigine versus placebo in the prophylaxis of migraine with and without aura. 913 45

We report a small open pilot study to evaluate the efficacy of lamotrigine (100 mg/day) in the prevention of migraine with aura attacks. We studied 24 patients affected by migraine with aura with a high frequency of attacks. Following a 1-month run-in period, the patients took lamotrigine for 3 months. Mean attack number per month was reduced from 6.1 +/- 4.1 during the run-in period to 0.7 +/- 1.3 at the 3rd month of treatment (p < 0.0001). In 13 out of 21 patients who completed the study, the attacks were completely abolished at the 3rd month of treatment, while only one patient was completely unresponsive to the drug. Lamotrigine seems worthy of a controlled trial as prophylaxis of a migraine with aura.
Cephalalgia 1999 Jan
PMID:Effectiveness of lamotrigine in the prophylaxis of migraine with aura: an open pilot study. 1009 62

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

The prophylactic management of recurrent head and facial pains may be challenging because of lack of efficacy and/or bothersome adverse effects of available drug therapies. New generation antiepileptic drugs offer new perspectives in difficult cases. We will review the available published data and present our experience with lamotrigine in various head and facial pains such as migraine, cluster headache, neuropathic trigeminal pain, atypical facial pain, and chronic tension-type headache. Twenty-five patients were enrolled and followed for 18 months. The dose was gradually increased in steps of 25 mg up to the effective dose (mean 250 mg/d). Lamotrigine was most effective in trigeminal neuralgia and dysesthesia, but was of little utility in the other head or facial pains.
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PMID:New generation anti-epileptics for facial pain and headache. 1137 75

Lamotrigine (LTG) as both effective against a wide range of seizure types and epileptic syndromes and well tolerated drug is being used in mono--as well as in polytherapy of pharmacoresistant epilepsy. The aim of this study was to evaluate the efficacy, safety and neuropsychological functioning after LTG (mean daily dose: 316 mg) as long-term monotherapy (12 mo) in 24 young adult out-patients (22.5 ys) with newly recognised and not-previously treated epilepsy in an open, non-comparative trial. 67% of patients were responders (above 50% reduction in seizure frequency) and 42% reported seizures remission. The best were results in patients with generalised convulsive fits (87% with remission). Adverse events in the early phase of medication in 21% of patients typically concerned CNS and gastrointestinal system (headache, asthenia, insomnia, nausea, gastric aches) and resolved spontaneously without treatment discontinuation. Biochemical examinations were normal and transient leucopenia and diminishion of MCV were clinically not significant. Neurodynamic abilities, neuropsychological examination results, memory verbal and visual tests and organic evaluation in organic triada tests did not show deterioration after LTG treatment. Slight difficulties in abstractive and operative thinking and some focal symptoms of fronto-temporal origin should be considered a result of drug but also the epilepsy per se. No significant differences in latencies and amplitudes of evoked potentials (VEP, BAEP, SEP and especially ERP-300) were measured after LTG. Preliminary results obtained in this study supported good efficacy and tolerability and especially lack of unfavourable influence of LTG on neuropsychological functioning in young previously untreated patients with epilepsy.
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PMID:Long-term monotherapy with lamotrigine in newly diagnosed epilepsy in adults. 1197 53

Accumulating data suggest that the antiepilepsy drug lamotrigine, which has been available for adult use for more than a decade, also confers broad-spectrum, well-tolerated control of epilepsy in children. The current study--the open-label continuation phase of several short-term clinical trials--was conducted to assess the long-term tolerability and efficacy of lamotrigine as open-label adjunctive therapy or monotherapy in pediatric patients for a variety of seizure types and syndromes including partial seizures, absence seizures, and Lennox-Gastaut syndrome. Clinic visits occurred every 24 weeks throughout the treatment period. A total of 252 patients under 16 years of age were enrolled in the study. The numbers of patients exposed to at least 48 weeks, 96 weeks, and 144 weeks of treatment with lamotrigine were 185 (73.4%), 119 (47.2%), and 60 (23.8%), respectively, for an average duration of exposure of 96.7 weeks. The most common adverse events considered by the investigator to be drug related were dizziness (9.1%), somnolence (7.9%), nausea (6.3%), vomiting (5.2%), and headache (5.2%). The most common serious adverse events (regardless of suspected cause) included pneumonia (3.0%) and infection (1.9%). Investigators judged that the overall clinical status of three-fourths of the patients had improved at treatment weeks 48 and 96 relative to prelamotrigine clinical status. Lamotrigine administered as monotherapy or adjunctive therapy for an average of 2 years (96.7 weeks) was well tolerated and effective in pediatric patients with partial or generalized epilepsy. These results complement and extend the large body of data demonstrating the tolerability and efficacy of lamotrigine with short- and long-term use in adults.
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PMID:Long-term tolerability and efficacy of lamotrigine in pediatric patients with epilepsy. 1208 84

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.
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PMID:New and emerging prophylactic agents for migraine. 1215 33

This open-label, 6-year continuation study of several short-term clinical trials was conducted to assess the long-term tolerability and efficacy of lamotrigine when used as adjunctive therapy or monotherapy for partial seizures in adult patients (> or =16 years) with epilepsy. Study visits occurred every 24 weeks throughout the treatment period. Of the 527 patients enrolled in the long-term continuation study, 508 were exposed to lamotrigine for at least 6 months (including their exposure in the primary clinical study), and 248 were exposed to lamotrigine for at least 5 years. Of the 527 patients, 75 received initial lamotrigine exposure during this study. Investigators judged that overall clinical status at the end of the study or at time of discontinuation (whichever occurred first) was improved moderately or markedly relative to prelamotrigine clinical status for 36% of patients. The most common treatment-emergent adverse events (regardless of suspected cause) were dizziness, diplopia, and headache. The only serious treatment-emergent adverse event occurring at a frequency exceeding 2% was accidental injury (2.7% of patients). Adverse events prompted 28 patients to discontinue from the study. The most common adverse events leading to discontinuation were dizziness (1.3%), headache (0.8%), rash (0.8%), and somnolence (0.6%). All adverse events resolved without sequelae. Lamotrigine administered as monotherapy or adjunctive therapy during a 6-year open-label continuation study was associated with a low incidence of adverse events in adult patients with epilepsy.
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PMID:Long-term tolerability of lamotrigine: data from a 6-year continuation study. 1475 Dec 4

Tolerability and safety are important considerations in optimising pharmacotherapy for bipolar disorder. This paper reviews the tolerability and safety of lamotrigine, an anticonvulsant recommended in the 2002 American Psychiatric Association guidelines as a first-line treatment for acute depression in bipolar disorder and one of several options for maintenance therapy. This paper reviews the tolerability and safety of lamotrigine using data available from a large programme of eight placebo-controlled clinical trials of lamotrigine enrolling a total of nearly 1800 patients with bipolar disorder. This review is the first to collate all the safety information from these clinical trials, including data from four unpublished studies. The results these trials in which 827 patients with bipolar disorder were given lamotrigine as monotherapy or adjunctive therapy for up to 18 months for a total of 280 patient-years of exposure demonstrated that lamotrigine is well-tolerated with an adverse-event profile generally comparable with that of placebo. The most common adverse event with lamotrigine was headache. Lamotrigine did not appear to destabilise mood and was not associated with sexual adverse effects, weight gain, or withdrawal symptoms. Few patients experienced serious adverse events with lamotrigine, and the incidence of withdrawals because of adverse events was low. Serious rash occurred rarely (0.1% incidence) in the clinical development programme including both controlled and uncontrolled clinical trials. These findings - considered in the context of data showing lamotrigine to be effective for bipolar depression - establish lamotrigine as a well-tolerated addition to the psychotropic armamentarium.
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PMID:Safety and tolerability of lamotrigine for bipolar disorder. 1475 79


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