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CATAMENIAL EPILEPSY FREQUENCY WITH VARIOUS ANTIEPILEPTIC DRUGS [P07.120]
Andrew G. Herzog, Wellesley, MA; Kristen M. Fowler, Sarah D. Smithson, Boston, MA; Laura Kalayjian, Christianne Heck, Sandra Oviedo, Guadalupe Corral-Leyva, Los Angeles, CA; Progesterone Therapy Study Group, Boston, MA
The term catamenial epilepsy has been used to describe a pattern of seizures that occur in synchrony with the menstrual cycle.1 Catamenial seizures may occur in as many as 40% of women with epilepsy, yet there is no generally accepted treatment for this seizure type. Some experts have suggested that naturally occurring progesterone metabolites may increase the seizure threshold in women with epilepsy by stimulating central nervous system γ-aminobutyric acid (GABA) receptors, and that an abrupt decline in circulating progesterone levels may therefore precipitate seizures in susceptible individuals.2,3 In this poster, Herzog et al examined whether the risk of catamenial seizures varied among women who used different antiepileptic drugs (AEDs) or adjunctive GABAergic medications.
The investigators performed an interim analysis of data from 285 female patients who participated in a randomized, multicenter controlled clinical trial that compared progesterone versus placebo for the treatment of intractable localization-related seizures. Detailed daily seizure diaries were used to identify women with evidence of catamenial seizures during at least 2 of 3 menstrual cycles during a 3-month baseline phase before randomization to study medication. During this baseline phase, the women used a variety of AED monotherapy and combination therapy regimens. The incidence of catamenial seizures was compared among groups of women during monotherapy with lamotrigine, carbamazepine, levetiracetam, phenytoin, or oxcarbazepine. The proportion of women with catamenial seizures was highest for those receiving carbamazepine monotherapy (12 of 18 women; 66.7%) and was lowest for women who were using lamotrigine monotherapy (7 of 20 women; 35%), although the differences in seizure rates for the various AEDs were not statistically significant (P = .10). When the investigators examined the incidence of catamenial seizures for the various polytherapy treatments that the women used during the 3-month baseline period, they again found a higher rate of catamenial seizures for women who used regimens that included carbamazepine (38 of 66 women; 57.6%) than lamotrigine (23 of 68 patients; 33.8%). This difference was statistically significant (P = .009). An examination of the effects of the concomitant use of GABAergic medications revealed that the incidence of catamenial seizures during the 3-month baseline period was significantly lower among women on monotherapy or polytherapy regimens who also used GABAergic medications (clobazam, clonazepam, valproate, gabapentin, tiagabine, and vigabatrin; P = .02). The decrease in the incidence of catamenial seizures with concomitant GABAergic medication was similar for patients who used treatment regimens that included either carbamazepine or lamotrigine.
These data suggest that the likelihood of catamenial seizures may be significantly related to the use of particular AED regimens. It is unclear whether this observation represents a difference in the neuronal effects of the various AEDs, variations in AED-induced hormonal changes, or another mechanism. A small prospective single-group study also recently found that 12 of 18 of women with catamenial epilepsy (67%) exhibited a decrease in seizure frequency of at least 50% from baseline with lamotrigine.4 Lamotrigine also significantly increased progesterone levels. Treatment strategies that include lamotrigine or GABAergic medications may be especially helpful for the control of catamenial seizures.
References
1. Penovich PE, Helmers S. Catamenial epilepsy. Int Rev Neurobiol. 2008;83:79-90.
2. Herzog AG. Hormonal therapies: progesterone. Neurotherapeutics. 2009;6:383-391.
3. El-Khayat HA, Soliman NA, Tomoum HY, et al. Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy. Epilepsia. 2008;49:1619-1626.
4. Gilad R, Sadeh M, Rapoport A, et al. Lamotrigine and catamenial epilepsy. Seizure. 2008;17:531-534.
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