Comparative cognitive effects of anticonvulsants

Meador, Kimford J.; Loring, David W.; Huh, Kyu Ha; Gallagher, Brian B.; King, Don W.

doi:10.1212/wnl.40.3_part_1.391

Cited by 197 publications

(102 citation statements)

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“…The specificity of the cognitive effects per drug appeared much more difficult to demonstrate. Recent reviews (9,10) suggest that the cognitive effects of the commonly used AEDs carbamazepine (CBZ) and valproate (VPA) are mild to moderate and do not have a large clinical impact on patients' daily lives, in contrast to the effects of "older" AEDs, in particular phenobarbitone and phenytoin. CBZ and VPA, therefore, are frequently used as the "gold standard" (1 I j to examine the cognitive effects of newer AEDs.…”

Section: Discussionmentioning

confidence: 99%

A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add‐On Therapy to Carbamazepine in Patients with Partial‐Onset Seizures

et al. 2000

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Summary: Purpose: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerabil‐ity and prevents cognitive impairment. Methods: The study is a multicenter, randomized, observer‐blinded, parallel‐group clinical trial with VPA or TPM given as first‐line add‐on therapy to steady‐state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25‐mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. Results: For the 10 baseline‐to‐end point comparisons, one test measuring short‐term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline‐to‐titration comparisons also show one statistically significant difference, again for a test measuring short‐term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. Conclusion: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).

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Section: Discussionmentioning

confidence: 99%

A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add‐On Therapy to Carbamazepine in Patients with Partial‐Onset Seizures

et al. 2000

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“…However, these were the only significant results from a total of 32 neuropsychological tests, and results were no longer significant when Bonferroni corrections were made. Meador et al (25) found no difference between CBZ and PHT but found that patients taking phenobarbitone performed significantly worse on one test (Digit Symbol) of eight. The remainder of the statistically significant results were found in single studies and are outlined in Table 8.…”

Section: Resultsmentioning

confidence: 99%

Neuropsychological Outcomes in Randomized Controlled Trials of Antiepileptic Drugs: A Systematic Review of Methodology and Reporting Standards

et al. 1998

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Summary:Purpose: To systematically review the methodology and use of neuropsychological tests in randomized controlled trials (RCTs) of antiepileptic drugs (AEDs) in patients with epilepsy.Methods: Trial reports were found by searching Medline 1966-1 996 and searching through journals by hand. Inclusion and exclusion criteria were applied, and methodological and neuropsychological test data was extracted by using a proforma.Results: 43 reports met our inclusion criteria, representing 40 RCTs, as three RCTs had generated two reports. Twenty-two were actively controlled, and 18 were placebo-controlled studies. Reporting of basic methods such as randomization method was poor. There has been no uniform approach to the use of neuropsychological tests, and a total of 87 has been used. The Stroop Colour Word Test and the Finger Tapping Test were most commonly used, at 13 times each, but were not used or reported in a uniform manner.Conclusions: Poor reporting of methods and the use of a plethora of neuropsychological tests create great difficulties for anyone wishing to make sense of currently available data. If we are better to understand the neuropsychological effects of AEDs, a more rational approach is needed, for which recommendations are made.

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“…5) Several clinical studies have reported no significant differences in the cognitive deficits elicited by carbamazepine, phenytoin or valproate treatments, [28][29][30] whereas phenobarbital has been reported to produce greater cognitive deficits than both carbamazepine and phenytoin. 31) Shannon and Love have reported that a single administration of phenobarbital, but not valproate, 30 min before an operant conditioning test impairs the working memory as assessed by spa- The rats were intraperitoneally injected with phenytoin (nϭ6-8), phenobarbital (nϭ8) or valproate (nϭ8-9) 30 min before the daily ECS administrations, and the open-field test was performed 24 h after the last ECS administration. The columns represent the meanϮS.E.M., * pϽ0.05, * * pϽ0.01 in comparison to the sham-ECS administered rats, † pϽ0.05, † † pϽ0.01 in comparison to the repeated ECS-administered rats (one-way ANOVA followed by Bonferroni's test).…”

Section: Discussionmentioning

confidence: 99%

Effects of Repeated Electroconvulsive Seizures on Spontaneous Alternation Behavior and Locomotor Activity in Rats

Hidaka

Suemaru

et al. 2008

Biological & Pharmaceutical Bulletin

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Comparative cognitive effects of anticonvulsants

Cited by 197 publications

References 0 publications

A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add‐On Therapy to Carbamazepine in Patients with Partial‐Onset Seizures

A Multicenter, Randomized Clinical Study to Evaluate the Effect on Cognitive Function of Topiramate Compared with Valproate as Add‐On Therapy to Carbamazepine in Patients with Partial‐Onset Seizures

Neuropsychological Outcomes in Randomized Controlled Trials of Antiepileptic Drugs: A Systematic Review of Methodology and Reporting Standards

Effects of Repeated Electroconvulsive Seizures on Spontaneous Alternation Behavior and Locomotor Activity in Rats

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