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Martha J Morrell

Publications and source records attributed to Martha J Morrell.

16 recordsLinked to original sources
PubMed2005

Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy.

Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.

Adolescent↗
PubMed2005

Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs.

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.

Adolescent↗
PubMed2005

Treatment of epilepsy in adults: expert opinion, 2005.

RATIONALE: Over the past decade, there has been a proliferation of new therapies for the treatment of epilepsy. Faced with this growing list of options, clinicians must decide what therapy, or combination of therapies, is best for a given individual. Although controlled clinical trials exist for each treatment option, the answer to these questions may remain unclear. In 2000, a survey of expert opinion was done to address questions concerning which treatment options might be best in a number of clinical situations. We surveyed a group of US epileptologists again in 2004 and compared the results of the two surveys. METHODS: We sent a questionnaire on the treatment of adolescent and adult epilepsy syndromes to a group of opinion leaders in the field of epilepsy. The questions were formatted to simulate real-world clinical situations in the treatment of symptomatic localization related epilepsy (SLRE) and idiopathic generalized epilepsy (IGE). The experts were asked to rate treatment options based on a modified RAND 9-point scale (with "9" most appropriate and "1" least appropriate). Statistical analysis of data was performed as defined by the expert consensus method. The results were used to develop user-friendly recommendations concerning overall treatment strategies and choice of specific medications. RESULTS: Of the 48 experts to whom the survey was sent, 43 (90%) responded; 29 (67%) of the respondents had also participated in the first survey. For initial monotherapy for IGE (generalized tonic-clonic [GTC], absence, and myoclonic seizures), valproate was rated as treatment of choice. For IGE-GTC seizures, lamotrigine and topiramate were also identified as usually appropriate for initial monotherapy. For IGE-absence seizures, ethosuximide was also a treatment of choice, and lamotrigine was usually appropriate. For SLRE, the experts were again asked to rate treatment options based on seizure type: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized tonic-clonic seizures (SGTC). In SLRE-SPS and SLRE-SGTC, carbamazepine and oxcarbazepine were treatments of choice, with lamotrigine and levetiracetam also usually appropriate. In SLRE-CPS, carbamazepine, lamotrigine. and oxcarbazepine were treatments of choice, while levetiracetam was also usually appropriate. For women who are pregnant or trying to conceive, lamotrigine was treatment of choice for both syndrome types. In the elderly, whether medically stable or ill, the treatment of choice was lamotrigine, while levetiracetam was also usually appropriate (along with gabapentin for persons with comorbid medical illness). In persons with HIV and epilepsy, lamotrigine and levetiracetam were usually appropriate. In people with both epilepsy syndromes who have depression, lamotrigine was treatment of choice. In a person with seizures and renal disease, lamotrigine was usually appropriate for both syndromes, with valproate also usually appropriate for IGE. In patients with hepatic disease, levetiracetam and lamotrigine were usually appropriate for IGE; in SLRE, levetiracetam was treatment of choice, with gabapentin also usually appropriate. CONCLUSIONS: Although the panel of experts reached consensus on many treatment options, there are limitations to these types of data. Despite this, the expert consensus method concisely summarizes expert opinion, and this opinion may be helpful in situations in which the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.

Adult↗
PubMed2005

Sex-steroid hormones in women with epilepsy.

Women with epilepsy face unique challenges, in part related to changes in the seizure threshold at various times in the menstrual cycle or during their reproductive life. Ovarian sex-steroid hormones alter the excitability of the central nervous system (CNS) and alter the frequency and severity of seizures. By understanding the effects of hormones on seizures, clinicians are better equipped to treat hormonally mediated epilepsy.

Aging↗
PubMed2004

Epilepsy and bone health in adults.

Adults taking antiepileptic drugs (AEDs) have an augmented risk for osteopenia and osteoporosis because of abnormalities of bone metabolism associated with AEDs. The increased fracture rates that have been described among patients with epilepsy may be related both to seizures and to AEDs. The hepatic enzyme-inducing AEDs phenytoin, phenobarbital, and primidone have the clearest association with decreased bone mineral density (BMD). Carbamazepine, also an enzyme-inducing drug, and valproate, an enzyme inhibitor, may also adversely affect bone, but further study is needed. Little information is available about specific effects of newer AEDs on bone. Physicians are insufficiently aware of the association between AEDs and bone disease; a survey found that fewer than one-third of neurologists routinely evaluated AED-treated patients for bone disease, and fewer than 10% prescribed prophylactic calcium and vitamin D. Physicians should counsel patients taking AEDs about good bone health practices, and evaluation of bone health by measuring BMD is warranted after 5 years of AED treatment or before treatment in postmenopausal women.

Adult↗
PubMed2004

Reproductive disturbances in patients with epilepsy.

In persons with epilepsy, both seizures and antiepileptic drugs can disturb reproductive health. For example, seizures can alter the release of hypothalamic and pituitary hormones, while some antiepileptic drugs alter concentrations of sex steroid hormones. Women with epilepsy are at increased risk for polycystic ovary syndrome and disorders of the menstrual cycle. Studies have found reduced fertility rates among men and women with epilepsy. The reasons for this reduction in fertility are likely to be both psychosocial and physiologic, and again, both epilepsy itself and antiepileptic drugs are implicated. Sexual dysfunction is common among patients with epilepsy and can have a somatic, psychological, or social basis. To provide the best care for patients with epilepsy, particularly women of reproductive age, clinicians must consider both the gender-based biology of epilepsy and the effects of antiepileptic drugs on reproductive health.

Anticonvulsants↗
PubMed2003

Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy.

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.

Adult↗
PubMed2003

Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs.

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 >or=50.

Absorptiometry, Photon↗
PubMed2003

Reproductive and metabolic disorders in women with epilepsy.

Epilepsy is a common neurologic disorder affecting women during the reproductive years. Seizures and some antiepileptic drugs (AEDs) can compromise reproductive health, and some AEDs can adversely affect carbohydrate and bone metabolism. Women with epilepsy have lower birth rates and more frequent anovulatory menstrual cycles. This appears to be related to seizure- and AED-associated reproductive endocrine disturbances. Carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PB) induce hepatic cytochrome P450 enzymes and lower endogenous estrogens, adrenal and ovarian androgens, and contraceptive steroids. Valproate (VPA) inhibits steroid hormone metabolism, elevates androgens, and predisposes to phenotypic signs of hyperandrogenism-hirsutism, obesity, acne, and frequent anovulatory cycles. VPA is associated with weight gain, probably by altering insulin metabolism. CBZ, PHT, and VPA, but not lamotrigine (LTG), are associated with lower levels of calcium. PHT, but not VPA or LTG, appears to accelerate bone turnover. AED effects on bone mineral metabolism may explain the elevated risk of fracture described in women with epilepsy. Prospective pregnancy registries are beginning to provide information about AED-associated teratogenesis. The North American Antiepileptic Drug Pregnancy Registry reports a 12% rate of major malformations after first trimester exposure to PB and an 8.6% rate after first trimester exposure to VPA. A prospective LTG-specific registry reports a 1.8% chance of major malformations after the first trimester. The registries will continue to release information as data become significant. In the meantime, practitioners can be alert to signs and symptoms of reproductive or metabolic health disturbances and participate in pregnancy registry efforts.

Abnormalities, Drug-Induced↗
PubMed2003

Review of lamotrigine and its clinical applications in epilepsy.

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.

Abnormalities, Drug-Induced↗
PubMed2002

Epilepsy in women.

Epilepsy in women raises special reproductive and general health concerns. Seizure frequency and severity may change at puberty, over the menstrual cycle, with pregnancy, and at menopause. Estrogen is known to increase the risk of seizures, while progesterone has an inhibitory effect. Many antiepileptic drugs induce liver enzymes and decrease oral contraceptive efficacy. Women with epilepsy also have lower fertility rates and are more likely to have anovulatory menstrual cycles, polycystic ovaries, and sexual dysfunction. Irregular menstrual cycles, hirsutism, acne, and obesity should prompt an evaluation for reproductive dysfunction. Children who are born to women with epilepsy are at greater risk of birth defects, in part related to maternal use of antiepileptic drugs. This risk is reduced by using a single antiepileptic drug at the lowest effective dose and by providing preconceptional folic acid supplementation. Breastfeeding is generally thought to be safe for women using antiepileptic medications.

Anticonvulsants↗
PubMed2002

Predictors of ovulatory failure in women with epilepsy.

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.

Adolescent↗
PubMed2002

Antiepileptic medications for the treatment of epilepsy.

Epilepsy is one of the most common neurological conditions encountered worldwide. The development of newer antiepileptic drugs (AEDs) has expanded over recent years, and the use of such drugs for indications other than epilepsy has also broadened. These factors insure that the majority of health care providers will be using an increasing number of AEDs in the care of their patients. Contained herein is a review of the mechanism of action of AEDs, individual drugs and their potential drug interactions, and general principles to guide the clinician in selection, implementation, and long-term monitoring of AEDs.

Anticonvulsants↗
PubMed2002

Treatment of women with epilepsy.

Epilepsy is equally prevalent in men and women. However, for women there are unique concerns related to hormone effects on seizures and the effects of seizures and antiepileptic drugs (AEDs) on reproductive health. Steroid hormones affect neuronal excitability and seizure frequency. Some AEDs reduce the efficacy of oral contraceptive agents, increasing the probability of unplanned pregnancies. AEDs affect bone density. AEDs may alter reproductive hormones resulting in polycystic-appearing ovaries, anovulatory cycles, and infertility. Seizure frequency may change during pregnancy, seizures may cause pregnancy complications, some AEDs are teratogenic, and many cross into breast milk. The treatment of a woman with epilepsy must consider all these issues.

Anticonvulsants↗
PubMedDate not supplied

Women with epilepsy: current treatment strategies.

Despite an ever-growing body of medical literature on epilepsy and its treatment, there are many clinical situations in which the best approach is unclear. In these situations, physicians may turn to expert opinion for guidance. Several methods exist for summarizing expert opinion. The least biased method is also the newest: the expert consensus method. When this method is used to analyze opinion regarding the treatment of women with epilepsy, it is clear that the selection of therapy is influenced by the sex of the patient.

Anticonvulsants↗