Effects of topiramate versus other antiepileptic drugs on the cognitive function of patients with epilepsy

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Abstract

BACKGROUND:

Only very large dose of topiramate has neurotoxicity, indicating that topiramate has low neurotoxicity and high safety. The residual rate of topiramate is affected by many cognitive-related adverse effects. Patients who take topiramate often accompany with thought slowness, difficulty in finding words, dyscalculia, blunt reaction, attention decreasing, memory deterioration, etc.

OBJECTIVE:

To compare the effects of topiramate with traditional anti-epileptic drugs (including carbamazepine and Valproic acid (VPA) on cognitive function of patients with epilepsy.

DESIGN:

Observational experiment, self-control and intergroup comparison.

SETTING:

Sichuan Academy of Medical Science.

PARTICIPANTS:

Eighty-seven inpatients and outpatients with newly diagnosed epilepsy who received preliminary diagnosis and follow-up in the Department of Neurology, Sichuan People's Hospital between January 2004 and June 2006 were involved in this survey. They were diagnosed according to disease history and electroencephalogram (EEG). The onset type was diagnosed following the definition of epilepsy and epileptic syndrome in 1989 International Anti-epileptic League. The involved patients and their relatives were informed of detection and therapeutic regimen. The patients were assigned into two groups according to table of random digit: traditional antiepileptic drugs group (AEDs group, n =44) and topiramate (TPM) group (n =43).

METHODS:

①Among the patients in AEDs group, carbamazepine was the first choice for 21 patients with partial seizures or partial secondarily generalized seizures, and VPA for 23 patients with generalized seizures. The initial dose of carbamazepine was 300 mg/d, and that of VPA was 500 mg/d. Patients in the TPM group took TPM with the initial dose of 25 mg/d, increased by 25 mg/d each week to target dose 150 mg/d within 8 weeks. ② Curative effect was graded into 4 degrees: markedly effective, effective, ineffective and aggravated. Total effective rate was calculated. ③ Cognitive function of patients was tested before and 6 months after administration by using Wechsler Adult Intelligence Scale(WAIS) or Wechsler Intelligence Scale for Children (WISC, Chinese edition), (Higher scores indicated better cognitive function), Stroop color word interference, test of memory of past numbers, test of telling the names of fruits and vegetables within 1 minute (Shorter time for reading word, telling color and memory of past numbers demonstrated better cognitive function. Less errors in reading words, telling colors and memory of past numbers, numbering and telling the names of fruits and vegetables within 1 minute indicated better cognitive function), etc. totally 22 items. ④ t test and paired t test were used for measurement data.

MAIN OUTCOME MEASURES:

Clinical curative effects and adverse reactions as well as neurological tests.

RESULTS:

Eighty-four pationts praticipated final analysis and 3 dropped out. ① Inthe AEDS group and TPM group, total effective rate was 86% and 99%, respectively. ② In the AEDs group, there were no significant changes in the scores of each test of WIS before and after treatment (P > 0.05). In the TPM group, total IQ, word scores, verbal IQ and digit span scores were significantly decreased (t =2.097 − 4.423, P < 0.05 − 0.01). Following treatment, the time for reading word and telling color for patients in the AEDs group was prolonged in Stroop color interference test (t = − 2.304, − 2.454, P < 0.05), and time for reading word and memory of past numbers for patients in the topiramate group was significantly prolonged (t = − 3.054, 2.272, P < 0.01, 0.05). ③ There were no significant differences in scores of WIS before and after treatment in AEDs group and TPM group (P > 0.05). Following treatment, verbal IQ, word scores, total IQ, digit span of patients in the TPM group were significantly lower than those in the AEDs group (t =2.052 − 3.297, P < 0.05 − 0.01). There were no significant differences in Stroop color word interference, memory of past numbers and telling the names of fruits and vegetables within 1 minute before and after treatment in AEDs group and TPM group (P > 0.05).

CONCLUSION:

① Moderate and small doses of both TPM and AEDs may lead to mild cognitive function impairment of patients, mainly presenting delayed reaction and decreased sensitivity. ②TPM mainly influences attention, language comprehension ability and fluency, while AEDs cause delayed reaction easily, but influence executive function mainly.

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