title: Ketter's hypothesis of the mood effects of antiepileptic drugs coupled to the mechanism of action of topiramate and levetiracetam.
abstract: Mood-modulating profiles of antiepileptic drugs (AEDs) have been classified by Ketter, Post, and Theodore [Neurology 1999; 53 (5, Suppl. 2) S53-76] into two classes: the first class is assumed to have deactivating effects related to GABA potentiation, and the second class is assumed to have activating effects that are associated with glutamate attenuation. We tested this hypothesis by reviewing the multiple mechanisms of action of topiramate (TPM) and levetiracetam (LEV) together with clinical behavioral side effects of patients who had been treated with TPM and LEV in a tertiary referral center for epilepsy. We found LEV to manifest activating and deactivating side effects equally and TPM to act as a deactivating AED, with tiredness/sleepiness side effects being predominant. TPM, in comparison to LEV, was found to be associated with a high incidence of side effects. Testing the hypothesis of Ketter et al. (1999) the deactivating effects of TPM may be coupled to a predominance of potentiation of GABA, but the oversimplified basis of the model needs to be acknowledged.
authors.affiliation: Department of Neurology and Neuropsychology, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands. gloriaroberts80@hotmail.com
authors.forename: G M P
authors.initials: GM
authors.lastname: Roberts
authors.forename: H J M
authors.initials: HJ
authors.lastname: Majoie
authors.forename: L A M
authors.initials: LA
authors.lastname: Leenen
authors.forename: H P
authors.initials: HP
authors.lastname: Bootsma
authors.forename: A G H
authors.initials: AG
authors.lastname: Kessels
authors.forename: A P
authors.initials: AP
authors.lastname: Aldenkamp
authors.forename: B E
authors.initials: BE
authors.lastname: Leonard
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D016009:Chi-Square Distribution; D003710:Demography; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005632:Fructose / Q000009:adverse effects* / Q000031:analogs & derivatives*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D019964:Mood Disorders / Q000145:classification / Q000209:etiology*; D016017:Odds Ratio; D010889:Piracetam / Q000009:adverse effects* / Q000031:analogs & derivatives*; D013997:Time Factors; D000077236:Topiramate; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D018698:Glutamic Acid; D000077287:Levetiracetam; D005680:gamma-Aminobutyric Acid; D010889:Piracetam