Vigabatrin

Abstract

Summary: Refractory epilepsies such as infantile spasms (IS) and complex partial seizures (CPS) can have a severe negative impact on the neurological integrity and quality of life of affected patients, in addition to drastically increasing their risk of premature mortality. Early identification of potentially effective pharmacotherapy agents is important. Vigabatrin has been shown to be a generally well tolerated and effective antiepileptic drug (AED) in a wide variety of seizure types affecting both children and adults, particularly those with IS and CPS. A bilateral, concentric constriction of the peripheral visual field characterizes the visual field defect (VFD) associated with vigabatrin, well characterized by numerous studies. This peripheral VFD presents in 30 -50% of patients with exposure of several years; however, most of these patients are asymptomatic. In well-controlled studies, the earliest onset in patients with CPS is 11 months and at 5 months in infants, with average onsets being more than 5 years and 1 year, respectively. Patients with a peripheral VFD retain an average 65°of lateral vision (normal, 90°). The fact that many patients never develop the vigabatrin-related peripheral VFD, despite long-term exposure at high doses, may support the hypothesis that the injury is an idiosyncratic adverse drug reaction (as opposed to a strict dose-or duration-dependent toxicity). Effective testing methods are available to aid in the early detection and management of the peripheral VFD. This article discusses issues of importance to clinical decision-making in the use of vigabatrin to assist the physician and patient in assessing the benefits of vigabatrin therapy and understanding the potential risks of the VFD and uncontrolled seizures.

Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review

“…In the last 10 years, 33 articles have evaluated pharmaceutical therapies in TSC 4,7,9,15,16,18,30,32,45,49,51,74,82,83,90,[112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129] . The recent literature on treatments for TSC with neurological manifestations expresses interest in pharmaceutical agents that prevent disease progression and control symptoms, as alternatives to surgical interventions.…”

Understanding and interpreting vision safety issues with vigabatrin therapy

“…Potential reasons for the variable prevalence rates include differences in the extent of drug exposure, variability in perimetric methods, unblinded assessments, relatively small sizes of the cohorts, retrospective nature of many studies, and sampling bias arising from the asymptomatic nature of the defect (19). The better evidence in the literature places the clinical study prevalence range at 30-50% (2,(33)(34)(35)(36)(37). Other sources (e.g., registry data and post-marketing surveillance) may indicate much lower rates overall.…”

“…The interim analysis of Study 4020 indicated that treatment with vigabatrin for more than 5 years was associated with 14.2-times the risk of developing a pVFD than treatment for less than 1 year (19). Based on the prevalence, distal appearance, lack of progression (in most cases), and lack of remission of pVFDs after discontinuing vigabatrin and the fact that many patients never develop vigabatrin-related pVFDs despite long-term exposure at high dosages, several investigators have proposed that the pathophysiology of the injury is an idiosyncratic adverse effect as opposed to a strict dosage-or duration-dependent toxicity (30,35,48,49).…”

Vigabatrin versus carbamazepine monotherapy for epilepsy

“…It can irreversibly inhibit the activity of GABA-transaminase, resulting in increased levels of GABA, an inhibitory neurotransmitter in the central nervous system (Petroff 1996;Wheless 2007). In animal seizure models, VGB-induced elevation of GABA levels have been associated with anticonvulsant activity (Gale 1986).…”