Effects of Vigabatrin on Cognitive Function and Mood When Used as Add‐on Therapy in Patients with Intractable Epilepsy

McGuire, Anna M.; Duncan, John S.; Trimble, Michael

doi:10.1111/j.1528-1157.1992.tb02295.x

Cited by 68 publications

(33 citation statements)

References 23 publications

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“…Four articles described neuropsychological testing used to detect drug-related changes in cognitive functioning; doses or serum levels were adequately reported (8,(33)(34)(35)…”

Section: Drug Toxicity Evaluated By Neuropsychological Testingmentioning

confidence: 99%

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Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

et al. 1997

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Summary: Purpose:We reviewed the literature to determine whether an analysis of published data could clarify the relationship between antiepileptic drug (AED) polytherapy and adverse affects (AE). We highlight the problems encountered.Methods: We made a Medline-search for articles published between 1974 and 1994 reporting the number of AE and doses or serum levels of every AED, per patient or treatment group, and used the PDD/DDD ratio to calculate AED load per patient from doses or the OSL/AToxL ratio to do so from serum levels of individual drugs. The PDD/ DDD is the sum of ratios of the actual prescribed daily doses divided by the published average therapeutic dose of each drug. The OSL/AToxL is the sum of each observed serum level divided by its average toxic level.Results: We retrieved 118 trial reports. Most had to be excluded because of incomplete reporting of concomitant medication or AE. The data of the 15 articles selected for further analysis indicate a relationship between drug load and number of AE. We noted no relationship between the number of AEDs administered and AE. In add-on studies, the difference in neurotoxicity between the active and placebo arm may be obscured if the relative increase in drug load is small, as exemplified by the study of McGuire et al. (35).Conclusions: Articles reporting add-on trials of new AEDs generally do not provide detailed information about the basic medication to which the new AED is added, which makes calculation of total drug load impossible. Furthermore, often only frequency of A E is reported, not severity or development of tolerance, making it difficult to judge the impact of AE. However, despite the paucity of available information, we present some evidence that toxicity in AED polytherapy may be related to total drug load, rather than to the number of drugs administered. Therefore, the present trend to reject polytherapy for fear of increased toxicity is not warranted, which removes one of the objections to initiating specific research to prove or disprove the value of AED combinations as long as the drug load is appropriate. Key Words: PolytherapyAntiepileptic drugs-Adverse effects-Drug loadEpilepsy.Antiepileptic drug (AED) pharmacotherapy is aimed at reducing seizure frequency and severity without producing adverse effects (AE). However, the reporting of AE in clinical trials lacks quantitative data because AE are often described in terms of frequency and rarely in terms of severity (1). Although the incidence of AE is important, the degree to which they occur also determines the acceptability of individual AEDs. When quantitative data are presented, a comparison is complicated because of the different rating scales used (2,3).The risk of development of chronic toxicity has been one of the arguments against use of polypharmacy in epilepsy (4). Much of this toxicity is believed Accepted January 13, 1997. Address correspondence and reprint requests to Dr. H. Meinardi, c/o P.O. Box 21,2100 AA Heemstede, The Netherlands.to be directly related to the number ...

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“…Four articles described neuropsychological testing used to detect drug-related changes in cognitive functioning; doses or serum levels were adequately reported (8,(33)(34)(35)…”

Section: Drug Toxicity Evaluated By Neuropsychological Testingmentioning

confidence: 99%

“…the difference in neurotoxicity between the active and placebo arm may be obscured if the relative increase in drug load is small, as exemplified by the study of McGuire et al (35).…”

mentioning

confidence: 99%

Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

et al. 1997

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“…In one study (McGuire et al 1992), tests of cognitive function and mood were performed in 15 Drug Safety 10 (5) 1994 Table VI. Adverse effects of vigabatrin in a study on its effects on infantile spasms in children (Luna et al 1989) Sedation 5 (7) Hypotonia 4 (6) Weight gain 4(6) Excitation, insomnia 3(4) patients before and 4 weeks after vigabatrin 2 g/day was added to their usual antiepileptic therapy.…”

Section: Psychiatric Effectsmentioning

confidence: 99%

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

Srinivasan

Richens

1994

Drug Safety

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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.

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“…Other studies report improved cognition in children [Camposano et al 2008] and in 66% of patients with epilepsy and psychosis . Improvements include better episodic memory, semantic memory and flexibility of mental processing in adolescents and adults and decreased arithmetic response time [McGuire et al 1992].…”

Section: Vigabatrinmentioning

confidence: 99%

The cognitive impact of antiepileptic drugs

Eddy¹,

Rickards²,

Cavanna³

2011

Ther Adv Neurol Disord

323

189

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Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evidence. Many studies have failed to investigate the influence of patient and treatment variables on cognitive functioning. Other difficulties include variation across studies in relation to design, treatment group and assessment tools, poor reporting of methodology and poor specification of the cognitive abilities assessed. Focused and rigorous experimental designs including a range of cognitive measures assessing more precisely defined abilities are needed to fill the gaps in our knowledge and follow up reported patterns in the literature. Longitudinal studies are needed to improve our understanding of the influence of factors such as age, tolerance and the stability of cognitive effects. Future trials comparing the effects of commonly prescribed agents across patient subgroups will offer critical insight into the role of patient characteristics in determining the cognitive impact of particular AEDs.

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Effects of Vigabatrin on Cognitive Function and Mood When Used as Add‐on Therapy in Patients with Intractable Epilepsy

Cited by 68 publications

References 23 publications

Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

Reappraisal of Polytherapy in Epilepsy: A Critical Review of Drug Load and Adverse Effects

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

The cognitive impact of antiepileptic drugs

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