Cognitive function in adult epileptic patients established on anticonvulsant monotherapy

Gillham, R. A.; Williams, N. M.; Wiedmann, Klaus D.; Butler, Elaine; Larkin, John G.; Brodie, Martin J.

doi:10.1016/0920-1211(90)90018-q

Cited by 52 publications

(27 citation statements)

References 23 publications

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“…These effects may be dose related [Gillham et al 1990], although one study reported no such relationship for cognitive-motor performance [Aman et al 1994]. Another study reported slowed performance on information processing tasks with phenytoin in comparison with carbamazepine, but no differences for memory or selective attention [Aldenkamp et al 1994].…”

Section: Phenytoinmentioning

confidence: 99%

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The cognitive impact of antiepileptic drugs

Eddy¹,

Rickards²,

Cavanna³

2011

Ther Adv Neurol Disord

319

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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Section: Phenytoinmentioning

confidence: 99%

“…Phenytoin has been implicated in declines in concentration, memory, visuomotor functions and mental speed [Pulliainen and Jokelainen, 1995;Gillham et al 1990;Andrewes et al 1986]. These effects may be dose related [Gillham et al 1990], although one study reported no such relationship for cognitive-motor performance [Aman et al 1994].…”

Section: Phenytoinmentioning

confidence: 99%

The cognitive impact of antiepileptic drugs

Eddy¹,

Rickards²,

Cavanna³

2011

Ther Adv Neurol Disord

319

189

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“…CBZ has been reported to have fewer adverse effects on cognitive function than other anticonvulsants (Trimble, 1987), although this view is not unanimous (Gillham et al, 1990). Impairment in psychomotor performance has been demonstrated after acute (Macphee et al, 1986a) and chronic dosing (Gillham et al, 1990;Macphee et al, 1986b) and correlates with increasing CBZ and CBZ-E concentrations (Gillham et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Monotherapy with conventional and controlled‐release carbamazepine: a double‐blind, double‐dummy comparison in epileptic patients.

Mckee

Blacklaw

Butler

et al. 1991

Brit J Clinical Pharma

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1 Twenty-one epileptic patients completed a double-blind, double-dummy, random order, crossover comparison of conventional carbamazepine (CBZ, Tegretol, CibaGeigy) with a new controlled-release formulation (CBZ-CR, Tegretol Retard). All participants were stabilised on maximally tolerated doses of CBZ as monotherapy (one twice daily, twelve three times daily, eight four times daily). Each preparation was taken with a matched placebo of the other for 4 weeks. 2 Peak serum CBZ concentrations (mean ± s.e. mean) were lower (CBZ 11.4 ± 0.4 mg 1-1; CBZ-CR 10.4 ± 0.5 mg 1-1; P < 0.01) and times to peak longer (CBZ 3.6 ± 0.5 h, CBZ-CR 5.2 ± 0.7 h, P < 0.01) during CBZ-CR treatment. Mean CBZ concentrations, however, were also slightly reduced with the new formulation (CBZ 9.9 ± 0.3 mg I-1; CBZ-CR 9.1 ± 0.5 mg 1-1, P < 0.05) and this was associated with greater seizure frequency (CBZ 2.8 ± 1.2, CBZ-CR 3.8 ± 0.9; P < 0.05) during the CBZ-CR treatment phase.3 Diurnal fluctuations (CBZ 41 ± 3%, CBZ-CR 28 ± 2%, P < 0.01) and variations (CBZ 53 ± 5%, CBZ-CR 33 ± 3%; P < 0.01) in serum CBZ concentration were substantially less with CBZ-CR and were similar to those calculated during a 6 or 8 hourly dosage interval with conventional CBZ (fluctuation 33 ± 3%, variation 42 + 5%). 4 Trough serum concentrations of the active metabolite CBZ 10,11 epoxide (CBZ-E)were lower on CBZ-CR (P < 0.05) than with conventional CBZ but no differences in peak or mean CBZ-E concentrations nor times to peak were found. Similar variations and fluctuations in CBZ-E concentrations were obtained with both formulations.5 Reaction times were longer (P < 0.05) and subjective side-effect scores higher (P < 0.05) shortly after dosing with conventional CBZ. 6 Blind patient preference significantly favoured CBZ-CR (fifteen CBZ-CR, two CBZ, four neither; P < 0.01). 7 CBZ-CR is a pharmacokinetically attractive method of administering CBZ and produces fewer subjective side-effects. However, the new formulation resulted in lower mean CBZ concentrations when given in the same total daily dose as the conventional preparation and may be less effective unless the dose is modified.

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“…7,12 Long term administration of phenytoin does not produce significant adverse effects on cognitive functions except some visually guided motor functions.dose of phenytoin is 300-500 mg and target range of plasma concentration is 5-25 µg/ml. 3 …”

Section: Phenytoinmentioning

confidence: 99%