To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy.
The charts of 811 outpatients with epilepsy who had received LTG and were seen at the ...Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels.
In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels (p < 0.0001): With levels <5.0 microg/mL, 7% of patients were toxic; with levels of 5 to 10 microg/mL, 14%; with 10 to 15 microg/mL, 24%; with 15 to 20 microg/mL, 34%; and with >20 microg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of >20 microg/mL.
There is a correlation between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 microg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 microg/mL). An initial target range of 1.5 to 10 microg/mL is suggested, though higher levels, up to >20 microg/mL, are often tolerated and can lead to additional efficacy in refractory patients.
Purpose: Three randomized, placebo-controlled trials have demonstrated the safety and efficacy of levetiracetam, a new antiepileptic medication, as add-on therapy for partial-onset seizures. The ...purpose of this study was to gather additional safety and efficacy data on levetiracetam in the real-world setting of community-based practice.
Methods: This was a phase IV prospective, open-label, multicenter, community-based trial. A total of 1030 patients (intent-to-treat (ITT) population) at least 16 years old (mean, 42.2 years) with partial-onset seizures were enrolled by over 300 investigators. Patients whose partial-onset seizures were inadequately controlled on their current medications had levetiracetam 500
mg bid added to their regimens. The levetiracetam dose was increased by 500
mg bid at the end of weeks 2 and 4 to a maximum dose of 1500
mg bid, unless the patient had been seizure-free during the preceding 2-week period. The dose was then to remain the same for 12 weeks. The main outcome measures were reduction in seizure frequency, global evaluation scale (GES), and adverse events.
Results: During the 16 weeks of the trial, 57.9% (542/936) experienced at least a 50% reduction in the frequency of partial-onset seizures, 40.1% (375/936) experienced at least a 75% reduction, and 20% (187/936) demonstrated a 100% seizure reduction. During the last 6 weeks of the study, 66.7% (500/750) experienced at least a 50% reduction in the frequency of partial seizures, 52.4% (393/750) experienced at least a 75% reduction, and 42.1% (316/750) demonstrated a 100% seizure reduction. On the investigator-completed clinical impression rating (GES), 74.3% (734/988) of patients were considered improved, with 37% of patients showing marked improvement. The most common adverse events were somnolence, dizziness, asthenia, and headache; these events were predominantly mild-to-moderate in nature.
Conclusions: These results provide further evidence regarding the efficacy and safety of levetiracetam as adjunctive treatment for partial-onset seizures.
Abstract Central sleep apnoea (CSA) occurs in up to 40% of patients with chronic heart failure (CHF). It is thought to be a consequence of CHF and is associated with an accelerated decline in cardiac ...function, and increased morbidity and mortality. The optimal treatment of CSA remains unclear. Resolution of CSA has been reported after cardiac transplantation. We report the first case of resolution of CSA 10 months following implantation of a permanent Jarvik™ 2000 left ventricular assist device (LVAD). The correction of CSA after implantation of the LVAD was associated with improvements in symptoms, exercise capacity, renal function, and increased arterial carbon dioxide levels at rest during wakefulness and also reduction in brain natriuretic peptide.
Women with epilepsy (WWE) are at increased risk for reproductive disorders. This study was designed to evaluate whether WWE are more likely to have anovulatory cycles and to assess the relative ...association of the epilepsy syndrome category and antiepileptic drugs (AEDs) to ovulatory dysfunction. Subjects included women aged 18 to 40 years not receiving hormones. Women without epilepsy (23 controls) and women with localization‐related epilepsy (LRE, n = 59) or idiopathic (primary) generalized epilepsy (IGE, n = 35) receiving either a cytochrome P450 enzyme (cP450) inducing AED (carbamazepine, phenytoin, and phenobarbital), a cP450 inhibiting AED (valproate), or an AED that does not alter cP450 enzymes (lamotrigine and gabapentin) in monotherapy for 6 months or more were followed for three menstrual cycles. A transvaginal ovarian ultrasound was obtained. Endocrine and metabolic variables were measured and luteinizing hormone sampled over 8 hours on days 2 to 5 of one cycle. Anovulatory cycles occurred in 10.9% of cycles in controls, 14.3% of cycles with LRE, and 27.1% of cycles with IGE. Of women using valproate currently or within the preceding 3 years, 38.1% had at least one anovulatory cycle in contrast with 10.7% of women not using valproate within the preceding 3 years. Predictors of ovulatory failure included IGE syndrome, use of valproate currently or within 3 years, high free testosterone, and fewer numbers of luteinizing hormone pulses, but not polycystic‐appearing ovaries. WWE are more likely to experience anovulatory menstrual cycles and the effects of epilepsy syndrome, and AED therapy may be additive. Women with IGE receiving valproate were at highest risk for anovulatory cycles, polycystic‐appearing ovaries, elevated body mass index, and hyperandrogynism. WWE with anovulatory cycles may have no other signs of reproductive dysfunction. Therefore, clinicians must be alert to this potential complication of epilepsy.
Arousal from sleep produces transient increases in systemic blood pressure, leading to the suggestion that repeated arousals are associated with a sustained increase in daytime blood pressure. Using ...data from the Wisconsin Sleep Cohort Study, a population-based study, we tested the hypothesis that sleep fragmentation is associated with elevated awake blood pressure. Sleep, breathing, and seated blood pressure measurements from 1,021 participants (age 42 +/- 8 yr; 590 males) were analyzed. Sleep fragmentation was defined as the total number of awakenings and shifts to Stage 1 sleep divided by the total sleep time (sleep fragmentation index: SFI). To reduce the confounding influence of sleep-disordered breathing, which is related to both increased daytime blood pressure and sleep fragmentation, all participants with an apnea-hypopnea index (AHI) > or = 1 were analyzed separately. Accounting for the influences of sex, age, body mass index, and antihypertensive medication use, the SFI was significantly associated with higher levels of awake systolic blood pressure in people with an AHI < 1; a 2 standard deviation increase in the SFI was associated with a 3.1 mm Hg rise in awake systolic blood pressure. In participants with an AHI > or = 1, there was no independent association between the SFI and awake blood pressure after controlling for the influence of the AHI.
In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had ...undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.
Levetiracetam (Keppra) was evaluated in a subset of patients aged ⩾65 years (
n=78) enrolled in a large (
n=1030) open-label, phase IV trial (the KEEPER trial). A 4-week dose adjustment was followed ...by a 12-week evaluation period. An overall median reduction in partial seizures of 80.1% (
n=65) was observed. Overall, 76.9% of patients were ⩾50% responders, 56.9% were ⩾75% responders, and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of patients reporting one or more adverse events. A total of 15 patients (19.2%) experienced an adverse event that led to discontinuation. Somnolence (
n=13,16.7%) and dizziness (
n=7,9.0%) were the most commonly reported adverse events. Despite the limitations of the open-label study design, these data provide information regarding the use of levetiracetam as add-on therapy for the treatment of partial-onset seizures in patients ⩾65 years of age, including those requiring concomitant medications.
Background: Valproate is used widely for the treatment of epilepsy but has been associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. The mechanism for these associations is unknown, ...but they have been hypothesized to be secondary to valproate-associated weight gain. This study was conducted to test the hypothesis that the antiepileptic drug lamotrigine, which also has a broad spectrum of anti-seizure efficacy, would not be associated with endocrine abnormalities and would not cause weight gain.
Objective and Methods: This open-label, cross-sectional study compared (1)
endocrine and lipid measures during the early follicular phase of the menstrual cycle; (2)
prevalence of menstrual disorders (from patient diaries recorded over three cycles); and (3)
body weight of women with epilepsy on lamotrigine monotherapy (
n=119) with those on valproate monotherapy (
n=103) for <5 years.
Results: Mean total serum testosterone and androstenedione levels were higher (
P<0.02) in the valproate group compared with the lamotrigine group. More lamotrigine patients (87%) than valproate patients (77%) reported regular menstrual cycles at the Screening Visit. The prevalence of anovulation did not differ between lamotrigine and valproate. Mean HDL cholesterol levels were higher (
P<0.01) with lamotrigine compared with valproate as were LDL and total cholesterol levels (
P<0.05). Mean total insulin levels did not significantly differ between the groups. Whereas mean body weight in lamotrigine patients did not differ between the time lamotrigine treatment was initiated and the Study Visit, mean weight in valproate patients increased by 3.7
kg.
Conclusions: Compared with lamotrigine monotherapy, valproate monotherapy was associated with weight gain and higher androgen levels in women with epilepsy. These data suggest that the hyperandrogenism observed in some women using valproate for epilepsy may be secondary to drug therapy. Lamotrigine monotherapy may be more appropriate than valproate for women in whom reproductive endocrine or metabolic abnormalities are potential concerns, i.e. women with concerns about weight gain, diabetes, hirsutism, polycystic ovary syndrome, menstrual dysfunction or infertility.
Women with epilepsy are believed to be at risk for sexual dysfunction. Disorders of sexual desire and sexual arousal, including dyspareunia, vaginismus, and lack of lubrication, affect an estimated ...30 to 60% of women with epilepsy. In this study, 57 reproductive-aged women with either localization related (LRE) or primary generalized epilepsy (PGE) on antiepileptic drug (AED) monotherapy and 17 nonepileptic controls completed questionnaires examining sexual experience, arousability, anxiety, and symptoms, as well as an inventory of depression. An endocrine assessment was performed during the early follicular phase of the menstrual cycle. Sexual dysfunction was more common in women with LRE, in women receiving phenytoin, in women with low levels of estradiol and dehydroepiandrosterone sulfate, and in women with self-reported symptoms of mild depression. The mechanisms of sexual dysfunction in women with epilepsy are multifactorial, but AED choice appears to be one cause that is modifiable.
Antiepileptic drug (AED) use is identified as being associated with increased fracture risk. AEDs commonly associated with osteopathies are inducers of the hepatic cytochrome P450 enzyme system ...(EIAEDs). We performed a retrospective cross-sectional study assessing bone mineral density (BMD) in an adult outpatient population receiving EIAEDs. Patients were routinely referred for dual-energy X-ray absorptiometry to evaluate BMD. BMD was measured at the femoral neck of hip and lumbar spine. Results were presented as absolute BMD (g/cm
2),
T score, and
Z score.
T and
Z scores were used in this analysis. As a group, those with BMD measurements represent people with intractable epilepsy. There were no statistically significant differences found in the
T or
Z scores by gender; therefore all analyses combined both men and women. Significant reductions in both
T and
Z scores were present in men and women <50 and ⩾50.
