Levetiracetam and Valproic Acid Improve Verbal Memory in Patients with High-Grade Glioma

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(ChemotherapyAdvisor) – Up to 50% of patients with high-grade glioma (HGG) experience seizures, but treatment remains a challenge. Treatment of HGG patients with antiepileptic drugs (AEDs) is problematic, as treatment results may be affected by drug interactions and overexpression of specific transporters in tumor cells; patients also appear to be particularly vulnerable to anti-epileptic medication side effects, including cognitive decline. But according to a retrospective study published in the journal Neuro-Oncology, patients receiving the AEDsvalproic acid or levetiracetam did not experience drug-related cognitive declines.

“Both AEDs even appeared to have a beneficial effect on verbal memory in these patients,” reported lead author Marjolein de Groot, MD, of the Department of Neurology at VU University Medical Center in Amsterdam, The Netherlands, and coauthors.

The cognitive effects of AEDs in patients with HGG have been little studied, the authors noted. So they reviewed neurocognitive function test results obtained from 117 patients before and after postoperative AED therapy was initiated. Attention, executive functioning, verbal memory, working memory, psychomotor functioning and information processing speed were tested among patients from three cohorts that had been undergone either monotherapy with an older AED (valproic acid or phenytoin; n=38) or monotherapy with the newer AED levetiracetam (n=35), or who underwent no AED therapy (n=44).

“Neither levetiracetam nor valproic acide was associated with additional cognitive deficits in HGG patients,” Dr. de Groot's team reported. Their findings “indicate that levetiracetam does not induce additional cognitive deficits in HGG patients and even improves verbal memory function. Valproic acid also seems to improve verbal memory, while phenytoin in particular is harmful to cognition in these patients.”

Patients administered levetiracetam fared better on verbal memory tasks than patients who were not administered any AEDs even after the authors controlled statistically for tumor location and lateralization. Tumor presence in the left hemisphere was related to poorer verbal memory (P=0.005), but levetiracetam remained significantly associated with superior verbal memory encoding and recall performance, compared to no AED therapy (P=0.003).

“Our findings provide arguments to consider prescribing either levetiracetam or valproic acid to epileptic HGG patients, especially those who have memory complaints,” the authors concluded.

Controlled clinical trials are needed to confirm and assess the “potential positive influence on cognition” of these AEDs, they cautioned.

The beneficial verbal memory effects associated with valproic acid “were obtained in post-hoc analyses and must thus be interpreted with caution,” the authors noted. “Previous reports on the effect of valrpoic acid are highly ambiguous. A number of studies in rats and humans have shown valproic acid to be associated with cognitive improvement in alertness, attention, and immediate recall, but the majority of studies report modest deterioration.”

Dr. de Groot reported receiving a grant from UCB Pharma which markets levetiracetam as Keppra.

Abstract

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