Efficacy Of Vigabatrin Research Articles

Long-term Safety and Efficacy of Vigabatrin in Japanese Patients with Infantile Spasms: A Multicenter Open-label Study

Long-term Safety and Efficacy of Vigabatrin in Japanese Patients with Infantile Spasms: A Multicenter Open-label Study

Vigabatrin in Low Doses Selectively Suppresses the Clonic Component of Audiogenically Kindled Seizures in Rats

The effect of systemic administration of the gamma-aminobutyric acid (GABA)-transaminase inhibitor vigabatrin (VGB) on different components of convulsions was tested in the model of audiogenically kindled seizures, which consist of brainstem (running, tonus) and forebrain (clonus) elements. Audiogenically susceptible rats of Krushinsky-Molodkina (KM), Wistar, and WAG/Rij strains received repeated sound stimulation (60 dB, 10-80 kHz) until kindled audiogenic seizures were reliably elicited. Kindled audiogenic seizures consisted of running, tonic, and generalized clonic phases in KM rats (severe audiogenic seizures) and of running and Racine stage 5 facial/forelimb clonus in Wistar and WAG/Rij rats (moderate seizures). Vehicle, 100, or 200 mg/kg of VGB was intraperitoneally injected 2, 4 and 24 h before the induction of kindled audiogenic seizures. At both doses, VGB did not change the seizure latency and the duration of running and tonic convulsions, but suppressed clonic ones in all rat strains. In KM rats, the mean duration of posttonic clonus was significantly reduced at 24 h after 100 mg/kg and from 4 h after 200 mg/kg. In Wistar and WAG/Rij rats, the mean duration of facial/forelimb clonus was reduced from 4 and 2 h after 100- and 200-mg/kg administration, respectively; 24 h after the high-dose injection, clonus was completely blocked in all rats of both strains. No difference in efficacy of VGB between Wistar and WAG/Rij rats was observed. VGB more effectively suppresses clonic convulsions than running and tonic ones in audiogenically kindled rats. It is supposed that this selective anticonvulsive effect of VGB results from different sensitivities of forebrain and brainstem epileptic networks to the presumed GABA enhancement.

Avaliação da eficácia e tolerabilidade da vigabatrina na síndrome de West

West syndrome (WS) is a severe epileptic encephalopathy of childhood, characterized by spasms, developmental deterioration and hipsarhythymia. To evaluate the safety and efficacy of vigabatrin (VGB) in the treatment of WS. We evaluated every patient diagnosed with WS seen at the pediatric epilepsy clinic and exposed to VGB. Patients were interviewed according to a semistructured questionnaire and we analyzed gender, age, etiology (cryptogenic or symptomatic), associated diseases, age of seizure onset, neuroimaging findings, EEG prior and after VGB, use of other antiepileptic drugs, time for seizure control, electroretinogram, visual complaints, adverse events and family history of epilepsy. Twenty-three patients were evaluated, 16 boys, ages ranging from 1.25 years to 11.5 years (mean=5y3m). Sixteen (69.5%) patients were seizure free, five (22%) had partial seizure control and in two (8.5%) there was no improvement. Only one patient presented gabaergic retinopathy. Six (26%) patients presented adverse events: somnolence, aggressivity or retinopathy. Patients with seizure onset after 6 months of age presented better results after VGB introduction (p<0.05). There was no difference in seizure control according to duration of epilepsy before VGB treatment or etiology of the seizures (p>0.05). After VGB, no patient presented hipsarrhythymia and 50% had a normal EEG. Although VGB may be associated with serious adverse events such as gabaergic retinopathy, our results show that it should be considered in the treatment of WS.

Vigabatrin for Infantile Spasms

The efficacy of vigabatrin (VGB) as the first, and adrenocorticotropin hormone (ACTH) or valproate (VPA) as the second, treatment of choice for newly diagnosed infantile spasms was evaluated in 42 infants treated at the University of Helsinki, Finland.

Safety and efficacy of vigabatrin and carbamazepine in ne wly diagnosed epilepsy: a multicentre randomised double-blind study

Vigabatrin is a newly licensed drug for use in patients with epilepsy. We investigated whether this drug was comparable to standard first-line monotherapy in efficacy and incidence of adverse events. We enrolled 459 patients with newly diagnosed, previously untreated partial epileptic seizures from 44 European centres and randomly assigned them carbamazepine 600 mg daily (n=230) or vigabatrin 2 g daily (n=229). After initial maintenance doses were reached, doses were adjusted downwards (in the case of adverse events) or upwards (in the case of seizures) by the clinician. The primary outcome was time to withdrawal because of lack of efficacy or adverse events. Secondary outcomes included efficacy (time to 6-month remission of seizures, time to first seizure after initial dose stabilisation), and adverse events (incidence and severity). Analysis was by intention to treat. Time to withdrawal for lack of efficacy or adverse events did not differ between groups (p=0.318). Vigabatrin was better tolerated than carbamazepine with fewer withdrawals, but was more frequently associated with psychiatric symptoms (58 [25%] vs 34 [15%]) and weight gain (25 [11%] vs 12 [5%]). Carbamazepine was associated with rash (22 [10%] vs seven [3%]). All efficacy outcomes favoured carbamazepine and failed to show equivalence between the two drugs. No significant difference was found for time to achieve 6 months of remission from seizures (p=0.058), but the most powerful outcome, time to first seizure after the first 6 weeks from randomisation, showed carbamazepine to be significantly more effective than vigabatrin (p=0.0001). Vigabatrin seems less effective but better tolerated than carbamazepine, which is the first-choice drug for the treatment of partial epilepsies. Vigabatrin cannot therefore be recommended as a first-line drug for monotherapy in this group of patients.

Open Comparative Long-term Study of Vigabatrin vs Carbamazepine in Newly Diagnosed Partial Seizures in Children

To compare vigabatrin with carbamazepine as monotherapy in newly diagnosed children with partial epilepsy in order to evaluate the efficacy and tolerability of both drugs. Open and randomized with a 2-year follow-up period. The Infantile Neuropsychiatric Division of the Regional Pediatric Hospital, Ancona, Italy. Seventy children with newly diagnosed partial epilepsy were treated with vigabatrin (38 patients) or carbamazepine (32 patients). Vigabatrin, 50 to 60 mg/kg per day, or carbamazepine, 15 to 20 mg/kg per day, split into twice-a-day doses. The efficacy and tolerability of vigabatrin were compared with those of the standard treatment (carbamazepine) for this patient group. The efficacy of vigabatrin and carbamazepine was similar, with the suggestion of a better side effect profile with vigabatrin. Vigabatrin monotherapy should be considered as a monotherapeutic treatment option in patients with newly diagnosed epilepsy. However, more studies are needed to evaluate other issues of concern, such as the cognitive and behavioral adverse effects of antiepileptic drugs, to determine the most suitable therapy.

Vigabatrin.

Vigabatrin (VGB) is a structural analogue of the inhibitory neurotransmitter gamma-amino butyric acid (GABA), which produces its antiepileptic effect by irreversibly inhibiting the degradative enzyme GABA-transaminase. This produces an increase in central nervous system (CNS) GABA levels. VGB is among the few antiepileptic drugs (AEDs) that was synthesized with a specific targeted mechanism in mind and was subsequently demonstrated to function by that mechanism. Tiagabine, a GABA reuptake blocker, is the only other "designer drug" among the currently available AEDs. Therefore, VGB is among the few AEDs for which the mechanism of action is well understood. Recently, safety issues have been raised with regard to the use of vigabatrin. This article reviews the mechanism of action, pharmacokinetics, safety, and efficacy of VGB.

Long-term treatment with vigabatrin – 10 years of clinical experience

This report describes the long-term follow-up of 56 patients with refractory partial epilepsy who, within 3 months of vigabatrin add-on therapy (3 g/day), showed a reduction in monthly seizure frequency of more than 50%. The short-term (6 months) and long-term (5 years) effects of vigabatrin on seizure frequency in this patient cohort have been published separately. The reduction in seizure frequency appeared to be long-lasting in the patients followed-up (n= 36) and, importantly, a significant number of the patients (n= 7) became seizure-free, especially during long-term treatment. Thus, the efficacy of vigabatrin appears to be progressive, at least in patients who show an early response to treatment. These results are consistent with experimental findings that suggest that vigabatrin may have anti-epileptogenic and neuroprotective effects.

The first-line use of vigabatrin to achieve complete control of infantile spasms

Vigabatrin was given as first-line therapy in 29 children with infantile spasms (IS). Vigabatrin monotherapy achieved complete control of spasms without subsequent relapse in 45% of patients. In all other patients, response was Partial or relapse occurred, and in these patients add-on therapy with tetracosactrin and/or clonazepam achieved a complete response. Side-effects with vigabatrin were mild and transient, and occurred in only four patients. The complete responses observed with vigabatrin occurred a short time after initiating treatment. These data further support the high efficacy of vigabatrin as first-line monotherapy for the treatment of IS.

Vigabatrin in uncontrolled seizures: Belgian clinical experience

The antiepileptic activity of vigabatrin has been established in several double-blind, placebo-controlled, clinical trials. The purpose of this study was to evaluate the efficacy and tolerability of this new antiepileptic drug in normal clinical practice rather than in controlled studies. A total of 102 patients (46 females and 56 males, ranging in age from 1 to 62 years) with previously uncontrolled seizures were treated with vigabatrin (0.5–4 g/day) as add-on medication, on an individual patient basis by 39 neurologists, for a mean duration of 235 days (range 30–520 days). Efficacy of vigabatrin was assessed after 3 months of therapy. Sixty-five patients (63.7%) showed a > 50% decrease in seizure frequency, and 12 patients (11.7%) became seizure-free. Thirty-one patients (29.4%) experienced a <50% decrease or no change in seizure frequency, and 6 patients (5.9%) had an increase in seizure frequency. Adverse events, nearly all of mild severity, were reported in 27 patients (26.5%). These data are remarkably similar to previous placebo-controlled studies and support that vigabatrin is beneficial to a significant number of patients with previously uncontrolled seizures.

Vigabatrin in the Treatment of Infantile Spasms

The anti-epileptic effect of vigabatrin as a first choice therapy was investigated in 6 children suffering from infantile spasms (IS). All 6 children showed a reduction in seizure frequency. Three children became seizure-free within a period of 2 weeks. Because our results suggest "an all or nothing phenomenon", a period of 2 weeks may be sufficient to evaluate the efficacy of vigabatrin in untreated infants suffering from IS. We suggest to use vigabatrin as a first choice anti-epileptic drug in infants with IS.

Efficacy and safety of vigabatrin in the long‐term treatment of refractory epilepsy.

1. The long term safety and efficacy of vigabatrin has been studied in 254 patients with refractory epilepsy (82% with partial seizures) in 23 different clinics in eight European countries. 2. This was an open multicentre study in which patients who had experienced a significant benefit from vigabatrin and had continued to take the drug for 1 year or longer were eligible for evaluation. The mean duration of therapy in the 254 patients was 22.7 months; 72 patients received vigabatrin for more than 2 years. 3. Patients were severely affected by epilepsy with a median monthly seizure frequency of 15.7 despite taking an average of 2.2 antiepileptic drugs. On vigabatrin, the median seizure frequency was about 35% of baseline, remaining stable over time despite a 10% reduction in the number of concurrent medications. 4. The lack of tachyphylaxis to the antiepileptic effect of vigabatrin is shown by the small number of patients who discontinued for insufficient efficacy (11%), two thirds of them during the first 6 months of follow-up. Maintenance of efficacy is also clearly demonstrated by analysis of 2 year and 3 year cohorts of patients. 5. Clinical and biological tolerability was excellent. There was a very low rate of drop out for adverse events (1.6%). Adverse events, mainly sedation, irritation and weight gain were mostly mild and transient. 75% of patients reported no adverse event at all. 6. Safety evaluation included serial neurological, ophthalmological and general examinations: no new abnormal clinical feature or adverse event emerged with long term therapy.

Response to vigabatrin in relation to seizure type.

1. The purpose of this study was to evaluate the efficacy of vigabatrin in relation to the seizure type. 2. A review of the literature concerning the efficacy of vigabatrin in clinical trials was performed. 3. To date, vigabatrin has been used in a small number of patients with generalized seizures: in this group no significant effect was noted. 4. Vigabatrin was also given to a large number of patients with complex partial seizures: in this group vigabatrin produced a greater than 50% decrease in seizure frequency in almost 50% of patients included. 5. This review provides evidence that vigabatrin is effective in the treatment of complex partial seizures: patients with only one seizure type, low seizure frequency and unifocal EEG abnormalities are particularly expected to respond. 6. This implies that patients with complex partial seizures do not constitute an homogeneous group and that various parameters should be considered in the evaluation of the response to treatment.