Differential Cognitive Effects of Carbamazepine and Gabapentin

Meador, Kimford J.; Loring, David W.; Ray, Paul H.; Murro, Anthony M.; King, Don W.; Nichols, Martha; Deer, E. M.; Goff, W. T.

doi:10.1111/j.1528-1157.1999.tb00858.x

Cited by 133 publications

(68 citation statements)

References 23 publications

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“…Reviewing the literature, it seems that TGB, similar to GABA A -or benzodiazepinereceptor agonists, evokes the impairment of acquisition and, additionallyFin contrast to these agonists, impairs the retrieval of the task. On the other hand, in patients with epilepsy, TGB and other GABA enhancers, such as GBP or VGB improved memory and cognitive functions (Kalviainen, 1998;Kalviainen et al, 1995;Mortimore et al, 1998;Meador et al, 1999). So far, considering the results of our study, as well as available evidence, it is difficult, at present, to unequivocally ascertain whether or not TGB disturbs the memory in animals.…”

Section: Controlcontrasting

confidence: 47%

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Łuszczki

Świąder

Parada-Turska

et al. 2003

Neuropsychopharmacol

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Polytherapy, based on the rational combining of antiepileptic drugs (AEDs), is required for patients with drug-resistant epilepsy. In such cases, the combinations of AEDs usually offer a significant enhancement of their protective effects against seizures. There has appeared a hypothesis that combining two AEDs, influencing the same neurotransmitter system, results in the potentialization of their anticonvulsant effects. For corroborating this hypothesis, a pharmacological character of interaction between tiagabine (TGB) and gabapentin (GBP)Ftwo novel AEDs affecting the GABA-ergic system, in the maximal electroshock seizure threshold (MEST)-test in mice was evaluated. TGB at the dose of 4 mg/kg and GBP at 75 mg/kg significantly raised the electroconvulsive threshold. Further, using the isobolographic calculations, TGB was coadministered with GBP at three fixed-ratios (1 : 3, 1 : 1, and 3 : 1) of their respective protective drug doses. All examined combinations of TGB with GBP exerted supra-additive (synergistic) interactions against MEST-induced seizures in mice. The interaction index, describing the strength and magnitude of interaction, ranged between 0.25 and 0.50 indicating supraadditivity. Adverse (neurotoxic) effects were evaluated in the chimney (motor performance) and the step-through, light-dark passive avoidance (long-term memory) tests in mice. The examined combinations of TGB with GBP did not affect the motor coordination, except for the fixed-ratio of 1 : 1, at which significant impairment of motor performance was observed. Moreover, all combinations selectively impaired the acquisition of the task in the passive avoidance test, having no impact on consolidation and retrieval in the longterm memory test. The pain threshold test revealed that the observed disturbances in the passive avoidance testing resulted presumably from the antinociceptive activity of these AEDs in combinations. After lengthening the exposing time to the direct current stimulus in the passive avoidance test from 2 to 6 s, the acquisition of the task, in animals receiving the combinations of TGB and GBP was not impaired. Neither the plasma, nor brain concentrations of GBP were affected by TGB application, so pharmacokinetic events that might negatively influence the observed effects are not probable. Results of this study clearly indicate that the activation of the same neurotransmitter system (GABA-ergic) leads to a synergistic interaction. The pain threshold test is a very good paradigm for screening the antinociceptive properties of AEDs, which may disturb the long-term memory testing in animals. Combinations of TGB with GBP (very promising from a preclinical point of view) should be clinically verified for elaborating the most effective treatment regimen in patients with intractable seizures.

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Section: Controlcontrasting

confidence: 47%

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Łuszczki

Świąder

Parada-Turska

et al. 2003

Neuropsychopharmacol

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“…Considering cognitive functioning, we found that these relatively well-controlled patients performed significantly worse on memory, selective and divided attention functions, and speed of information processing than the matched healthy controls. The diminished speed of information processing we found has also been established by pharmacological studies and might be due to medication [32]. REM sleep deprivation for example, caused by CBZ, might have affected cognitive performance, although the magnitude of this effect compared with other epilepsy-related characteristics remains controversial [33].…”

Section: Discussionmentioning

confidence: 93%

Cognition and health-related quality of life in a well-defined subgroup of patients with partial epilepsy

Engelberts¹,

Klein

Ploeg

et al. 2002

Journal of Neurology

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To investigate the extent and nature of the objective and subjective cognitive deficits and health-related quality of life (HRQOL) in adult outpatients with relatively well-controlled partial epilepsy without symptomatic aetiology, who were on carbamazepine (CBZ) monotherapy. Furthermore, we studied the influence of the epilepsy history and medication on various cognitive functions and the HRQOL. 56 outpatients (29 male, 27 female, mean age 41.3 years) with partial epilepsy were compared with 56 age-, gender-, and education-matched healthy controls. Patients were tested on attention, memory, speed of information processing, and executive functioning. Questionnaires aimed at measuring self-perceived cognitive functioning (CFQ) and HRQOL (SF-36) were administered. Mann Whitney-U tests were used to compare the two groups. Linear regression analysis was performed to identify the epilepsy and medication-related factors that are associated with cognitive functioning and HRQOL. Patients scored lower on measures of attention (P = 0.03), learning (P = 0.02) and speed of information processing (P = 0.00). Mental aspects of HRQOL such as fatigue were lower (P = 0.00), whereas physical functioning was unaffected. These patients also expressed reductions in mental functioning as indicated by a low self-perceived cognitive functioning (P = 0.01). Age at onset, duration of epilepsy, seizure type, seizure frequency, localisation, years on CBZ, and CBZ dosage were not related to cognitive functioning or HRQOL. Patients with partial epilepsy, even when able to maintain regular jobs, have impaired cognition and HRQOL that cannot be attributed to their epilepsy history or CBZ dosage or years of CBZ intake. Therefore, physicians should be more aware of their cognition and HRQOL, in addition to the antiepileptic drug regime.

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“…Most studies tend to report little or no cognitive impairment in association with gabapentin, including double-blind studies [Dodrill et al 1999;Meador et al 1999;Leach et al 1997], and there may be potential for improved performance in cognitive measures [Mortimore et al 1998]. …”

Section: Gabapentinmentioning

confidence: 99%

The cognitive impact of antiepileptic drugs

Eddy¹,

Rickards²,

Cavanna³

2011

Ther Adv Neurol Disord

324

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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Differential Cognitive Effects of Carbamazepine and Gabapentin

Cited by 133 publications

References 23 publications

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Tiagabine Synergistically Interacts with Gabapentin in the Electroconvulsive Threshold Test in Mice

Cognition and health-related quality of life in a well-defined subgroup of patients with partial epilepsy

The cognitive impact of antiepileptic drugs

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