oa Editorial [Vigabatrin: An Antiepileptic Drug with Major Benefits but Significant Adverse Effects]

As is the case for most drugs, vigabatrin (VGB) has major advantages and also has significant adverse effects. However, the situation for VGB is somewhat unusual. The drug was prescribed for many years before Eke et al. [1] reported peripheral visual field defects (VFDs) in three adult patients. Other adverse effects [2], including psychiatric changes and transient MRI abnormalities have been reported but will not be discussed here. VFDs appear to be common, having been found in 25% to 50% of adult patients taking VGB [2]. Although the VFDs are asymptomatic in most patients [3, 4], this must be viewed as a serious adverse effect. For example, those with horizontal visual fields less than 120° are not permitted to hold a driving licence. Visual acuity is not usually affected and, although those with VFDs retain an average lateral visual field of 65° [5] (i.e., 130° horizontal), sometimes the visual field constriction may be severe [3]. There is debate about whether the VFDs are reversible [6, 7] but a number of reports have suggested that they are not [8, 9]. Does the emergence of this frequent, serious, and possibly irreversible adverse effect imply that VGB should no longer be prescribed or should be withdrawn from the market? The recent FDA approval would suggest that this is certainly not the case. What is the justification for the availability of this drug? VGB is almost unique in having an apparently single, intended mode of action, namely inhibition of GABA-transaminase, the enzyme that breaks down the inhibitory neurotransmitter GABA, with result that GABA concentrations in the brain are increased. It can be of benefit in treating partial-onset seizures in some patients for whom no other drug has been effective. VGB also has a major role to play in the treatment of infantile spasms, a very severe form of epilepsy with a high risk of poor outcome, both in terms of ongoing seizures and in terms of significant cognitive impairment [10]. If the infantile spasms are secondary to tuberous sclerosis, VGB appears to be particularly effective; in the initial studies 100% of the babies became spasm free [11]. In subsequent studies the response rate has been less but has remained very high. The other effective treatment for infantile spasms is ACTH or steroids, which can be also associated with serious adverse effects [10]. How is the clinician to weigh the risk of the serious adverse effect of VFDs against the possible advantage of good seizure control? In the case of partial-onset seizures, the decision-making process might be easier because the advantages and disadvantages can usually be discussed directly with the patient, who can then make an informed decision. However, this is not always the case. One of my patients was a wheelchair-bound teenager with severe learning disability (mental retardation) and severe epilepsy, in whom good seizure control had been achieved with VGB. Another clinician stopped the VGB because of concerns about the possibility of VFDs. If this patient had developed visual field constriction, it would almost certainly not affected his quality of life, which was much more severely impaired by his other problems and which was certainly very severely decreased when the uncontrolled seizures returned. After consultation with his carers, the VGB was re-instituted, with a good response. The remainder of the discussion will concentrate on infantile spasms because the situation with this severe form of epilepsy is very different. Because the onset is typically around 4 to 9 months of age, it is up to the parents or carers to decide on treatment, in discussion with the clinician. Concerns about possible VFDs may weigh heavily with parents. They might also have difficulty in appreciating what the implications of this possible adverse effect could be for their child. What guidance can be given? To answer this question, further information is required. Perhaps the best way of considering this situation is to ask a series of additional questions. Several of these issues are discussed in the excellent review by Willmore et al. [2]. Have visual field defects been described in children who took VGB for infantile spasms as infants? What is the minimum period or minimum dose of VGB that has resulted in apparently permanent visual field defects? If the VGB is stopped at the first sign of VFDs, will this adverse effect be less than it would have been if the VGB had been continued? Is there any evidence that treating infantile spasms promptly and effectively changes prognosis, particularly with regard to cognitive outcome? Which is superior in treating infantile spasms, VGB or ACTH/steroids; should different treatments be favoured in different circumstances?