Safety and efficacy of vigabatrin and carbamazepine

Abstract

David Chadwick and colleagues (July 3, p 13)1Chadwick D Vigabatrin European Monotherapy Study Group.Safety and efficacy of vigabatrin and carbamazepine in newly diagnosed epilepsy: a multicentre randomised double-blind study.Lancet. 1999; 354: 13-19Summary Full Text Full Text PDF PubMed Scopus (154) Google Scholar conclude that vigabatrin is less effective but better tolerated than carbamazepine in the treatment of newly diagnosed partial epilepsy and that therefore vigabatrin cannot be recommended as a first-line drug for monotherapy in this group of patients. However, although they mention the risk of developing concentric visual field defects on vigabatrin, this safety issue has not been taken into account in their recommendations, which seem solely based on their study results. The occurrence of severe symptomatic concentric visual field defects has been reported in patients since 1997.2Eke T Talbot JF Lawden MC Severe persistent visual field constriction associated with vigabatrin.BMJ. 1998; 314: 180-181Crossref Scopus (434) Google Scholar The prevalence of symptomless field defects under vigabatrin is estimated at about 30%.3Revised SPC of Sabril, June, 1999.Google Scholar Evidence suggests that visual field defects are irreversible even after discontinuation of vigabatrin. The precise mechanism of action is unclear but Baulac and colleagues4Baulac M Bordmann JP Lanoé Y Severe visual field construction and side-effects of GBA-mimetic antiepileptic agents.Lancet. 1998; 352: 546Summary Full Text Full Text PDF PubMed Scopus (39) Google Scholar have suggested a direct toxic effect by γ-aminobutyric acid on the retina. Severe symptomatic visual field defects implies functional blindness, but the functional impact of symptomless defects should also not be underestimated. Symptomless here merely means that the patient is not aware of the defect, but that interference with normal functioning might have started much earlier. Moreover, before visual field defects become symptomatic, in the sense of being recognised by the patient, the defect must be substantial. There is, however, no rationale for waiting until symptomless visual defects become symptomatic because irreversible harm will have been done. The Committee for Proprietary Medicinal Products (CPMP) reviewed the benefit/risk profile of vigabatrin with special emphasis on this safety issue. As was indicated in a letter to doctors issued by the marketing authorisation holder, the indication for vigabatrin should be restricted to addon therapy in both adults and children, but only after all other appropriate drug combinations have failed. The risk/benefit profile for vigabatrin as monotherapy, taking into account Chadwick's findings is negative. For infantile spasms the benefit/risk profile is regarded as acceptable since alternatives with a more favourable profile are lacking. Safeguards for early detection of visual field defects by periodic perimetry are recommended, although in young children validated methods for detecting visual field defects need to be developed. Safety and efficacy of vigabatrin and carbamazepineAuthor's reply Full-Text PDF