A Risk-Benefit Assessment of Vigabatrin in the Treatment of Neurological Disorders

Abstract

Vigabatrin was designed to increase the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. It does this by replacing GABA as a substrate for the action of the catabolic enzyme GABA-transaminase. As a result of this inhibition, neuronal GABA levels are elevated, resulting in enhanced endogenous GABA transmission. A number of clinical trials assessing the effect of vigabatrin in epilepsy have been completed. Vigabatrin is of proven benefit in partial seizures and secondarily generalised tonic clonic seizures, and it is licensed for use as adjunctive therapy in these conditions in several European countries. It has been shown to be effective in some epilepsy syndromes in children including West's syndrome, infantile spasms and cryptogenic partial seizures. Its effect on primary generalised tonic clonic seizures is variable, while there is considerable evidence that it has a deleterious effect on myoclonic and absence seizures. There have been a few reports of the benefits of vigabatrin in other neurological disorders including tardive dyskinesia, degenerative ataxias and GABA metabolism disorders. The adverse effects associated with vigabatrin are similar to those seen with other anticonvulsants, with a predominance of CNS effects including somnolence, fatigue, irritability, dizziness and headache. Psychiatric symptoms including depression and psychosis are seen in a small number of patients and cause the most problems. These often necessitate discontinuation of vigabatrin, which usually results in resolution of symptoms.

Concurrent Illnesses in Adults with Childhood‐Onset Epilepsy: A Population‐Based 35‐Year Follow‐Up Study

“…Kokkonen (23), however, reported the overall prevalence of mental disorders to be similar in patients with childhood-onset epilepsy (17%) and in age-matched controls (22%). In contrast to some previous studies (36)(37)(38)(39)(40)(41)(42), our population-based, unselected study, did not show AEDs to have any significant independent attributive effect on the occurrence of psychiatric or psychosomatic comorbidity.…”

“…Distribution of occupations in the general employed population aged[25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] years living in the study area, in a printing company in Turku (the TS-Group), in patients with childhood-onset epilepsy only, and in the two control populations(%) were classified according to a modification of the International Classification of Diseases(21). For statistical analyses, the following tests were used: Pearson's chi-square test with Yates' correction when appropriate, Fischer's exact test (two-tailed), McNemar's test of symmetry, Mann-Whitney U test, and logistic and stepwise logistic regression.…”

The Potential for Vigabatrin‐Induced Intramyelinic Edema in Humans

“…VGB provides effective seizure control and has a relatively benign clinical adverse-event profile, with the most commonly reported side effects being headache, drowsiness, fatigue, and dizziness (1). Overall, the treatment of epilepsy patients with VGB demonstrates an acceptable risk-to-benefit ratio.…”

Alteration of Cardiac Function in Patients with Temporal Lobe Epilepsy: Different Roles of EEG‐ECG Monitoring and Spectral Analysis of RR Variability

“…The effect of PB on heart function also was evaluated, and it does not seem to have any effect on cardiac conduction (33,34). No effect of VGB on the autonomic control of cardiac function has been described (35).…”