Epilepsia
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Male and female sexuality and reproductive functions are complex systems with cortical, limbic system, hypothalamic, pituitary, and end organ interactions. Sexual steroids are produced in the sexual glands, the adrenals, and the brain. They undergo interconversion in the brain, bind to different brain areas, and have multiple effects behaviorally and neurophysiologically. ⋯ AEDs alter contraceptive hormone treatments. Information on the effects of new AEDs is being gathered by the National Pregnancy Registry. Catamenial epilepsy and some sexual dysfunction in men may be treatable.
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Data accrued from clinical trials of five new antiepileptic drugs (AEDs) are compared for efficacy in reducing seizures and self-reported adverse events as a basis of selection among new AEDs. Drawbacks to use of these data also are demonstrated. ⋯ Comparisons of data for five new AEDs provide information for selection among treatments when a second drug is needed to improve control of CPSs. However, significant differences among the control groups and other problems make comparisons between trials problematic. The final choice should be based on the need of the individual patient for superior seizure control versus minimal adverse effects.
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Gabapentin (GBP) is a antiepileptic drug (AED) indicated as adjunct therapy for treatment of partial seizures, with and without secondary generalization, in patients 12 and older with epilepsy. GBP (1-(aminomethyl) cyclohexaneacetic acid) is structurally related to gamma-aminobutyric acid (GABA), which readily crosses the blood-brain barrier. Radiolabeled GBP binds throughout the central nervous system in anatomic areas important in treatment of seizures. ⋯ Although efficacy occurs at lower levels, increased GBP doses are associated with additional efficacy. Reports suggest that initiation at 2,400 mg or 3,600 mg may not be associated with increased adverse experiences. Titration to 900 or 1,200 mg on the first day of GBP therapy appear to be well tolerated.
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The success of carbamazepine (CBZ) as a broad-spectrum antiepileptic drug (AED) has led to its use as first-line therapy in children and adults for partial and generalized tonic-clonic seizures. The limitations of CBZ include toxicity in sensitive individuals, autoinduction, which requires dose adjustment when therapy is initiated, and chronic hepatic induction, producing drug interactions when CBZ is used with AEDs and other drugs that undergo hepatic metabolism. One of two main products of CBZ microsomal metabolism, CBZ-10,11-epoxide (formed by oxidation of the double bond between C-10 and C-11), appears to provide antiepileptic efficacy but contributes significantly to clinical toxicity. ⋯ Controlled clinical trials, reported in the mid- to late 1980s, led to approval of OXC in many European countries, and now in over 50 nations around the world. United States multicenter clinical trials have recently been completed, and at this writing the drug is awaiting approval by the FDA. This article reviews the pharmacology, animal data, outcomes of published controlled clinical trials, postmarketing data, adverse experiences, and current recommendations for clinical use of OXC.