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Biomedical subjects

Cynthia L Harden

Publications and source records attributed to Cynthia L Harden.

17 recordsLinked to original sources
PubMed2006

Optimizing therapy of seizures in women who use oral contraceptives.

There is no evidence that oral contraceptives (OCs) increase seizure activity, and OC use in the setting of antiepileptic drug (AED) treatment provides pregnancy prevention at among the highest rates of any available contraceptive method. One concern, however, is the increased risk for OC failure with the use of cytochrome P450 3A4 enzyme-inducing AEDs, such as phenobarbital, carbamazepine, phenytoin, felbamate, topiramate, and oxcarbazepine. Felbamate induces metabolism of only the progestogenic component, whereas topiramate induces metabolism of only the estrogenic component. There is preliminary evidence that lamotrigine induces the metabolism of a progestin, levonorgestrel. It is unclear whether the estrogenic or the progestogenic component is more clinically important in preventing pregnancy. To ensure maximal pregnancy prevention, it is therefore recommended that women taking enzyme-inducing AEDs should receive OCs containing at least 50 mug of ethinyl estradiol and that low-dose formulations in general should not be used. AEDs that do not induce cytochrome P450 3A4 enzymes, including valproic acid, gabapentin, levetiracetam, tiagabine, vigabatrin, zonisamide, and pregabalin, do not interact with OCs. There are no concerns regarding the treatment of seizures or increased pregnancy risk with the use of OCs and these non-enzyme-inducing AEDs. Lamotrigine levels, however, are reduced by 50% in the setting of OC use. Therefore, women with epilepsy taking lamotrigine need to be monitored carefully for seizures when OCs are started and for toxicity when OCs are discontinued. Dose adjustment to maintain clinical stability may be necessary in these settings. The placebo or pill-free week of the OC regimen may also be a period when clinical toxicity can occur. Even with the considerations discussed in this review, OCs are a reasonable contraceptive option for women with epilepsy taking AEDs.

Anticonvulsants↗
PubMed2006

Sexuality in men and women with epilepsy.

Most people with epilepsy maintain normal reproductive and sexual lives. However, a significant minority of women with epilepsy (20% to 30%) have some degree of sexual dysfunction, including problems with libido, arousal, and orgasm. Men with epilepsy are at risk for decreased sexual functioning, including sexual interest and sexual performance, at least in part because of increased sex hormone-binding globulin levels and lower bioactive testosterone levels, particularly in association with the use of enzyme-inducing antiepileptic drugs, such as phenytoin and carbamazepine. A decrease in bioactive testosterone levels probably has a significant effect on the sexuality of women with epilepsy as well. Antiepileptic drugs may also affect sexual function in women through alterations of serotonergic neurotransmission. Epilepsy itself appears to have the potential to affect sexual function. The amygdala is emerging as a brain structure with significant involvement in sexuality in patients with epilepsy, as shown by alterations in sexual functioning after temporal lobectomy. Preliminary evidence suggests that people with temporal lobe epilepsy have reduced genital blood flow in response to erotic stimulation; the etiology of this phenomenon is not well understood, but disruption of the limbic and frontal cortex by epileptic activity may be implicated. Psychosocial factors, including sexual anxiety and stigma associated with epilepsy, can also affect the sexual life of patients with epilepsy.

Amygdala↗
PubMed2006

Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study.

PURPOSE: Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. METHODS: This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. RESULTS: Twenty-one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA. CONCLUSIONS: CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.

Anticonvulsants↗
PubMed2005

Sexuality in women with epilepsy.

Most women with epilepsy maintain normal reproductive cycles and sexual lives. However, a significant minority, approximately 20-30%, have some degree of sexual dysfunction, including problems with seizure exacerbation, libido, arousal, and orgasm. Fluctuating hormone levels may contribute to an array of reproductive cycling abnormalities. With regard to sexual dysfunction, there is some evidence of reduced genital blood flow in women with temporal lobe epilepsy. Other studies suggest that psychosocial factors, such as depression, feeling stigmatized, and being anxious about having seizures during sex, may contribute to the higher rates of sexual dysfunction in this patient population. Some antiepileptic drugs may adversely affect normal reproductive cycling and sexual function, particularly drugs that increase serotonergic transmission. Conversely, resective epilepsy surgery has been shown to restore sexual function. Treatments for sexual dysfunction include testosterone replacement, although transdermal testosterone replacement is not yet approved by the Food and Drug Administration for women. Given the possibility that women with epilepsy may experience inadequate vasocongestion during arousal, sildenafil may have a useful role, though it has not proved effective for women in general. This review focuses on potential sexual problems that are faced by women with epilepsy, with the suggestion that proper treatment may alleviate these problems.

Anticonvulsants↗
PubMed2004

Frequency of catamenial seizure exacerbation in women with localization-related epilepsy.

This investigation assessed the frequency of catamenial epilepsy in 87 women who charted seizures and menses during three cycles. Catamenial epilepsy designation was made if two of three cycles showed at least one of three previously defined catamenial patterns. Among ovulatory cycles, average daily seizure frequency was significantly greater during the perimenstrual and preovulatory phases. Among anovulatory cycles, average daily seizure frequency was substantially less during the midfollicular phase than during the remainder of the cycle. Overall, 39.1% of the women had catamenial epilepsy.

Adolescent↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, I: Treatment of new-onset epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs [AEDs; gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS), reviewed in the order in which these agents received approval by the U.S. Food and Drug Administration] in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 until September 2002, with selected manual searches up to 2003. RESULTS: Evidence exists, either from comparative or dose-controlled trials, that GBP, LTG, TPM, and OXC have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. Evidence also shows that LTG is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Efficacy and tolerability of the new antiepileptic drugs, II: Treatment of refractory epilepsy: report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society.

PURPOSE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox-Gastaut syndrome. CONCLUSIONS: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.

Acetates↗
PubMed2004

Reaction to epilepsy in the workplace.

PURPOSE: The purpose of this study was to determine the characteristics of epilepsy that produce avoidant behavior in the workplace and therefore contribute to the actual stigma that persons with epilepsy are subjected to on the job. METHODS: We developed a survey consisting three vignettes briefly describing a coworker with either depression, multiple sclerosis, or epilepsy. Each vignette was followed by eight identical questions addressing the level of comfort during interactions with the vignette subject. The epilepsy vignette did not describe a seizure. The surveys were hand-distributed in two companies in New York City and returned anonymously by mail. The results of the responses to each illness were compared by chi2, and the responses were correlated with demographic information by using Pearson's correlation. RESULTS: Seventy-four of 200 distributed questionnaires were returned. Respondents reported more anxiety at the thought of interacting with a coworker with epilepsy than with depression or multiple sclerosis, but this difference did not reach significance. Worry about sudden, unpredictable behavior for the coworker with epilepsy was significantly greater than that with multiple sclerosis (p = 0.014). The level of comfort regarding providing first aid for the coworker with epilepsy was significantly less (p = 0.018) than that for depression and multiple sclerosis. Lower job level and lower income level correlated with more social discomfort for all three illnesses. CONCLUSIONS: The idea of a having a coworker with epilepsy may produce some social avoidance. However, the worry about a sudden, unpredictable event and the discomfort regarding providing first aid for a coworker with epilepsy is significant when compared with that with depression or multiple sclerosis. These findings suggest that education about first aid for epilepsy will reduce the worry and discomfort surrounding persons with epilepsy in the workplace.

Adult↗
PubMed2003

Menopause and bone density issues for women with epilepsy.

Menopausal women with epilepsy present several unique management challenges. They have an elevated risk for osteoporotic fracture because of the adverse effects of antiepileptic drugs (AEDs) on bone metabolism, combined with the chance of trauma during seizures and the subtle effects of AEDs on coordination that promote falling. A uniform effect of AEDs on vitamin D metabolism or bone turnover has not yet been revealed by clinical or basic studies, although the enzyme-inducing AEDs appear to decrease serum vitamin D levels. However, bone density is frequently decreased in patients with epilepsy. Clinicians must be familiar with the recommendations for calcium and vitamin D supplementation and recognize when to refer patients for bone density evaluations. Perimenopause is a transition during which women with epilepsy are at risk for increased seizure frequency, probably because of alterations in the estrogen:progesterone ratio over this period. Women with epilepsy who have had a catamenial seizure pattern during their reproductive years are at particular risk for an increase in seizure frequency during perimenopause but may experience a seizure reduction after becoming menopausal (cessation of menses for 1 year). These women appear to represent a subgroup of patients with epilepsy who have heightened sensitivity to endogenous reproductive hormone levels. The use of hormone replacement therapy may also increase seizure occurrence. Finally, the age at menopause may be reduced in women with poorly controlled seizures. This is probably related to an effect of seizures on hypothalamic function, although primary ovarian dysfunction may also be operative in this setting.

Adult↗
PubMed2003

The diagnostic significance of video-EEG monitoring findings on pseudoseizure patients differs between neurologists and psychiatrists.

PURPOSE: The diagnosis of psychogenic pseudoseizures has improved with the availability of video-electroencephalography (EEG) monitoring; however, the outcome of this difficult disorder has remained poor. In an attempt to elucidate factors contributing to this poor outcome, we hypothesized that neurologists and psychiatrists differ in their views of the diagnosis and management of psychogenic pseudoseizure patients. METHODS: The hypothesis was tested by using a brief anonymous questionnaire administered to neurologists and psychiatrists at continuing medical education (CME) conferences. RESULTS: We found that neurologists and psychiatrists differ significantly in their opinion as to the accuracy of the video-EEG procedure; psychiatrists view video-EEG as often inaccurate in the diagnosis of psychogenic pseudoseizures compared with neurologists (p < 0.001). Neurologists, more frequently than psychiatrists, thought that patients' own psychopathology rather than "doctors dropping the ball" was a predominant factor in contributing to therapeutic failure, but this difference between specialties did not reach statistical significance. CONCLUSIONS: Resolving the differences between neurologists and psychiatrists would be helpful in caring for psychogenic pseudoseizure patients. These results support the need to encourage psychiatrists to have an integral involvement in epilepsy centers and to improve the understanding of psychogenic pseudoseizures in both disciplines.

Attitude of Health Personnel↗
PubMed2002

The co-morbidity of depression and epilepsy: epidemiology, etiology, and treatment.

Co-morbid depression is common in patients with epilepsy and is often undiagnosed. The manifestation of depression in epilepsy is multifaceted with many interacting neurobiological and psychosocial determinants, including clinical features of epilepsy (seizure frequency, type, foci, or lateralization of foci) and neurochemical or iatrogenic mechanisms. Depression is reported more frequently in patients with temporal lobe epilepsy (TLE) and left-sided foci, although not all studies support this finding. In patients with depression and epilepsy, optimal control of seizures should be attained first and foremost with appropriate anticonvulsant treatments including antiepileptic drugs (AEDs) and vagus nerve stimulation (VNS) therapy. Some anticonvulsant treatments (VNS, valproate, carbamazepine, lamotrigine, and gabapentin) have demonstrated mood improvement in epilepsy patients and may have therapeutic potential for this patient population. When antidepressants are necessary to treat depression in patients with epilepsy, selective serotonin reuptake inhibitors (SSRIs) and multireceptor antidepressants are considered first-line treatments. Electroconvulsive therapy is not contraindicated for treatment-resistant or psychotic depression. Depression must be recognized, diagnosed, and adequately treated in patients with epilepsy.

Anticonvulsants↗
PubMed2002

Mood disorders in patients with epilepsy: epidemiology and management.

Patients with epilepsy are at high risk for depression because of an incompletely understood combination of factors that may be both psychosocial and neurological. Interictal depression in patients with epilepsy is an undertreated condition, in part because of concern regarding drug interactions and the risk of exacerbating seizures with antidepressant treatment. Bipolar disorder is not described as occurring with a higher than expected frequency in the population with epilepsy, but high rates of depression and suicide are well recognised, highlighting the need for more emphasis on antidepressive treatment in this group of at-risk patients. Neurological factors, including site and lateralisation of seizure focus, may be important for the development of depression, with left-sided seizure foci having a higher association with depressive symptoms. Forced normalisation may be a factor in the paradoxical onset of depression in patients with epilepsy whose seizures suddenly become well controlled by anti-seizure treatment. Lowering of folic acid levels by some antiepileptic drugs (AEDs) may also influence the expression of depression in patients with epilepsy. New AEDs continue to emerge as beneficial treatments themselves for mood disorders, with lamotrigine, gabapentin and, to a lesser extent, topiramate having clinical trials data to support their use in patients with bipolar disease. Similar positive data are available for vagal nerve stimulation. Mood effects of AEDs can be complicated, however, as many of these drugs (e.g. tiagabine) have also been reported to cause depression as an adverse effect. Electroconvulsive therapy in depressed patients with epilepsy requires special consideration. The selective serotonin reuptake inhibitors (SSRIs) and antidepressants that act at multiple receptors (e.g. nefazodone, venlafaxine) are the most appropriate treatments for depressed patients with epilepsy. Among these agents, citalopram has a low risk of interactions with AEDs. Bupropion, clomipramine and maprotiline are associated with a greater risk of seizures compared with other antidepressants and consequently should be used with caution in the treatment of depression in patients with epilepsy.

Anticonvulsants↗
PubMedDate not supplied

Polycystic ovaries and polycystic ovary syndrome in epilepsy: evidence for neurogonadal disease.

Polycystic ovary syndrome (PCOS) is a mysterious reproductive disorder that results in subfertility. The underlying causes are not known, and even the definition is a moving target. Women with epilepsy have features of PCOS at a higher than expected rate, and polycystic ovaries (PCO) also are present at high rates in this population. Valproate is associated with weight gain and increased androgen levels, two features of PCOS. This review proposes that epilepsy, with its known adverse effects on luteinizing hormone pulsatility, could be a cause of PCOS and that valproate could be an imitator, if not also a cause of the syndrome.

Journal Article↗