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Is Thin Better Than Smart? Cognitive Effects of an Anticonvulsant

Topiramate use was associated with broad cognitive decline in healthy volunteers.

Off-label use of anticonvulsants has become ubiquitous for many neuropsychiatric conditions, but these drugs might have significant adverse consequences. Patients on topiramate, which is frequently prescribed to promote weight loss, have complained of cognitive problems. To learn more about this drug's potential cognitive effects, researchers randomized 40 healthy volunteers to receive gabapentin, topiramate, or placebo for 12 weeks. Dosages were started low and increased gradually (topiramate: starting dosage, 25 mg/day; maximum, 400 mg/day; gabapentin: starting dosage, 300 mg/day; maximum, 3600 mg/day). The researchers performed a wide range of neuropsychological tests at baseline and after 12 weeks (minimum of 14 days at plateau dosages; medians: topiramate, 330 mg/day; gabapentin, 3600 mg/day).

Of the six primary cognitive measures, four revealed significant declines in performance with topiramate, compared with gabapentin or placebo. For example, in a measure of verbal fluency, topiramate was associated with a median decrease of 18 words, compared to 1 word with gabapentin and none with placebo. More than half of topiramate recipients had significant decrements (>2 standard deviations) on tests of graphomotor skills, memory, and verbal fluency. On a test that correlates with full-scale IQ, median scores in the topiramate group decreased from 113 to 93. Although there were no significant changes among the groups on the self-report measures for confusion, fatigue, or depression, high within-group variability may have obscured any differences.

Comment: The magnitude of these cognitive changes is impressive, especially considering that this was a nonclinical population. Impairments may be even greater in neuropsychiatric populations, particularly in individuals with preexisting cognitive difficulties. We need to discuss potential problems with topiramate users, to monitor cognition, and to assess the relative benefits and risks of prescribing the drug in the first place.

— Jonathan Silver, MD

Published in Journal Watch Psychiatry April 6, 2005

Citation(s):

Salinsky MC et al. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology 2005 Mar 8; 64:792-8.

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