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Menopausal Women with Epilepsy

Online Heath Chat with Adele C. Viguera, MD, MPH

September 17, 2009 | Reviewed on February 11, 2014 by Adele C. Viguera, MD, MPH

Introduction

Cleveland_Clinic_Host: Despite the fact that more than one million women are expected to reach menopause each year, the relationship between menopause and epilepsy, as well as, treatment interventions for menopausal-related symptoms, have not been systematically investigated.

While women with epilepsy (WWE) are likely to experience menopausal symptoms including hot flushes, night sweats, sleep disturbance, and mood symptoms which may substantially impact quality of life, there are no epidemiologic studies examining the prevalence or severity of these symptoms among WWE.

With respect to treatment of typical menopausal symptoms, fewer women are receiving hormonal replacement therapy (HRT) given the recent findings from the Women’s Health Initiative (WHI) of reported health risks including cardiovascular events and breast cancer, leaving many women symptomatic. Moreover, treatment with HRT may pose additional risks for WWE including an increase in seizure frequency and altered clearance of some antiepileptics (AEDs). Given these treatment obstacles, it is remarkable that to date, there are no published studies on the efficacy of alternative treatments to HRT, such as serotonin reuptake inhibitors (SSRIs), for menopause-related symptoms in women with epilepsy.

Adele C. Viguera, MD, MPH, is Director of the Center for the Care and Study of Women’s Mental
Health at Cleveland Clinic. She studied at Dartmouth Medical School, Massachusetts General Hospital, McLean Hospital and Harvard University.

Dr. Viguera completed her medical internship at the Massachusetts General Hospital before starting her psychiatry residency at McLean Hospital in Belmont, Massachusetts. She completed a clinical fellowship in Consultation-Liaison Psychiatry and a fellowship in Perinatal and Reproductive Psychiatry at MGH. She has played an important role in the program’s growth into a nationally recognized clinical and research center addressing a wide range of reproductive-associated psychiatric syndromes including premenstrual dysphoric disorder, antenatal mood disorders, postpartum depression, and peri and postmenopausal mood disturbance. Her leadership within the Program has been complemented by dedication to teaching and mentoring psychiatric residents, fellows, medical students, and junior faculty over the past ten years.

Dr. Viguera was the Associate Director of the Perinatal and Reproductive Psychiatry Clinical Research Program at Massachusetts General Hospital since 1997, and Assistant Professor of Psychiatry at Harvard Medical School. She joined the Cleveland Clinic staff in October 2007, and continues to lead research efforts in women’s mental health.

With respect to research, Dr. Viguera has had very successful track record securing support to study important research questions in reproductive psychiatry. Early in her academic career, she was the recipient of an NIMH K23 Career Development Award (K23 MH-11609), focused on The Course of Bipolar Disorder in Pregnancy and the Postpartum Period.

In 2003, she also earned a Masters degree in Public Health in Quantitative Methods at the Harvard School of Public Health as part of her K23 grant. She has received additional awards from private foundations including two consecutive National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator research Awards for the study of Neonatal Outcome Following Exposure to Lithium.

In 2004, she received a two-year Harvard Medical School Scholars in Medicine Fellowship Claflin Award for a project entitled, Screening for Antenatal Bipolar Disorder associated with Maternal Morbidity and Adverse Neonatal Outcome. The body of research laid the groundwork for an R01 award in 2005 from The National Institute of Mental Health for a multi-site collaborative study with Emory School of Medicine on Bipolar Disorder in Pregnancy: Predictors of Morbidity (Collaborative Grant: R01 MH 071762 [Viguera]; R01 MH 071531[Newport]). The study is currently in progress.

Dr Viguera’s major research interests include:

  1. longitudinal course and treatment of psychiatric illness during pregnancy and the postpartum period
  2. efficacy of antidepressant therapy for premenstrual dysphoric disorder, postpartum psychiatric illness, and perimenopausal mood disturbance
  3. perinatal and neurobehavioral sequelae of maternal psychiatric illness on child development
  4. psychotropics and lactation
  5. efficacy of hormone therapy for the acute and prophylactic treatment of mood disturbance in women.

With her family’s recent move to Cleveland, Dr. Viguera will lead research efforts in women’s mental health at the Cleveland Clinic, as well as, continue her collaboration Massachusetts General Hospital.

For more information on Dr. Adele Viguera's research studies or to make an appointment with a specialist in the Center for the Care and Study of Women’s Mental Health at Cleveland Clinic, please call 216.636.5860 or toll-free at 866.588.2264; or you can visit us online at clevelandclinic.org/psychiatry.

Cleveland_Clinic_Host: Welcome to our Online Health Chat with Dr. Adele Viguera. We are thrilled to have Dr. Adele Viguera here today for this chat. She is considered an expert in the field women’s mental health and reproductive-associated psychiatric syndromes. Let’s begin with some general questions.


Perimenopausal Mood Symptoms

daniella: Are mood changes I experienced during perimenopause the same as post-menopausal symptoms? If not, how do they differ and how can I treat them differently?

Speaker_Dr__Adele_Viguera: Yes, the symptoms are essentially the same. Let me discuss some facts about perimenopause and mood symptoms.

Depressive symptoms, including minor, subsyndromal depression as well as major depression, are common during the perimenopause. Recently, two community-based prospective cohort studies established the perimenopause as a significant period of risk for occurrence of major depression. Investigators found that women had a 2–2.5 fold increased risk of major depression during the perimenopause compared to older reproductive-age women. Moreover, these investigators also found that nearly a third of the women studied experienced their first major depressive episode during the perimenopausal transition.

susan: I am perimenopausal and experiencing mood swings, particularly depression. Why is that?

Speaker__-_Dr__Adele_Viguera: This relates to the etiology of Perimenopausal Depression. Several theories have been advanced to explain the increased risk for major depression during the perimenopause. Some propose the “domino theory” which argues that depression is an indirect consequence of a cascade of symptoms (hot flashes leading to sleep disruption leading to major depression) resulting from changes in estradiol levels during the perimenopause. Other evidence suggests that estrogen withdrawal has a direct effect on brain regions involved in mood regulation. Another theory is that life transitions in midlife (“empty nest syndrome”) increase the likelihood of major depression during the perimenopause.


Menopause and Depression

avery: I've been diagnosed with depression. Is it possible my mood problems are hormonal? And what are my options for treating my depression during menopause?

Speaker__-_Dr__Adele_Viguera: Yes, it is possible that your mood problems are hormonal, but treatment of this type of depression is not necessarily different from non-hormonally induced depression. It is well known that there is a sub-group of women who are particularly vulnerable to depression during times of hormonal fluctuations. Some women develop premenstrual dysphoric disorder; some women are more vulnerable than others to postpartum mood disturbance and some women are more vulnerable to depression during the perimenopausal transition. We approach treatment in one of several ways:

  1. If a patient has a previous history of major depression, we are more likely to recommend treatment with an antidepressant in addition to therapy. In terms of medication choice, we would typically recommend an antidepressant the patient has responded to in the past.
  2. If the patient is experiencing depression for the first time during the menopausal period and she has concomitant vasomotor symptoms, we may consider treatment with HRT first. However, for women with epilepsy this may be problematic since there is some evidence to suggest that HRT may have a negative effect on seizure frequency. Therefore, we would be more inclined to treat this hormonally driven mood disorder with an antidepressant, and there is robust evidence that antidepressant treatment (adequate dose for adequate duration of time) is effective in treating such a depression.

Menopause and Epilepsy: What is the Relationship?

langforrd: What does menopause have to do with my seizure disorder? Have there been any studies on the relationship between hormonal fluctuations and epilepsy?

Speaker_-_Dr__Adele_Viguera: Data suggest that some premenopausal patients with epilepsy are particularly susceptible to developing seizure exacerbations in association with the normal menstrual cycle hormonal fluctuations (i.e. also known as “catamenial epilepsy). Some investigators have argued that for these patients, menopause may represent a period of marked decreased in seizure frequency given the relative lack of hormonal fluctuations and the hypogonadal state, but this is not always the case and further studies are needed to understand this relationship.

barley: My doctor says I have catamenial epilepsy. What exactly does that mean?

Speaker__-_Dr__Adele_Viguera: Catamenial epilepsy is defined as seizures that occur with your menstrual cycle. Having this kind of epilepsy may  predispose a patient to an increase in seizure frequency during the perimenopause which is characterized by unpredictable and chaotic hormonal fluctuations.

chasellen: Can my epilepsy medication affect or even mask my menopausal symptoms?

Speaker__-_Dr__Adele_Viguera: Of all the anticonvulsants, Gabapentin® is the only anticonvulsants we have data suggesting that it can help reduce or potentially “mask” hot flashes. There are no data available yet on the other anticonvulsants. It is important to note that there are some important interactions with anticonvulsants and hormones including  the birth control pill and hormone replacement.

Some anticonvulsant levels may be lowered by the hormonal intervention and some of the anticonvulsants may reduce the levels of the birth control pill thus making it less effective. Be sure to check with your doctor and/or local pharmacist about any important interactions between these medications.


Epilepsy Medication and Menopause

chasellen: Will my epilepsy medication change after menopause?

Speaker__-_Dr__Adele_Viguera: No, not necessarily. You and your doctor should continue to monitor your epilepsy medication as you did prior to menopause. However, with age,your body may not be able to clear your anticonvulsant as efficiently as it did when you were younger. Therefore, it is important that your anticonvulsant levels be monitored closely and the dose adjusted accordingly.

ks2: What might be some preferred approaches to treating seizures during the perimenopausal/menopausal time of life? What do you think of hormone replacement therapy as a way to maintain a more consistent hormonal pattern – and specifically, the use of natural (yam-based) progesterone?

Speaker__-_Dr__Adele_Viguera: Progesterone does not treat menopausal symptoms per se as effectively as estrogen. However, hormonal replacement therapy may be problematic for women with epilepsy since the preliminary evidence suggest that it may increase seizure frequency. In addition if you are having breakthrough seizures during the perimenopause/menopause,we would recommend adjusting your anticonvulsant medication dose accordingly.

If you are experiencing severe vasomotor symptoms and have epilepsy, consider other non-hormonal interventions. There is good evidence for the efficacy of some of the SSRIs and SNRIs for the treatment of vasomotor symptoms including citalopram (celexa), escitalopram (lexapro),paroxetine (Paxil) fluoxetine (Prozac), venlafaxine(Effexor), desvenlafaxine (Pristique), and duloxetine (Cymbalta). There are data supporting the use of one of the anticonvulsants , gabapentin (Neurontin) in the treatment of vasomotor symptoms.

melanie: My sleep patterns are very abnormal since I have begun menopause which is beginning to cause me issues throughout my day. Is there something that I can take to help regulate this sleep irregularity that won’t interact with my epilepsy medication?

Speaker__-_Dr__Adele_Viguera: Sleep disruption is a common problem during the menopause in women with hot flashes Sleep problems increase significantly as women transition from premenopause to perimenopause. The quality of sleep is also reduced in about 40% of women. Menopausal women are often unaware of their nocturnal hot flashes and the severity of their sleep disruption. A “menopausal insomnia syndrome” is diagnosed in women who awaken spontaneously with hot flashes and have difficulty maintaining sleep at least 3 nights per week.

Data from several studies suggest that treatment with a sleeping medication for women suffering from menopausal symptoms can be very helpful. Such medications include zolpidem (Ambien®) and eszopiclone (Lunesta®). The data suggest that these medications not only help with sleep but with other menopausal symptoms including quality of life.

Peri- and post-menopausal women frequently complain of insomnia or poor sleep quality. Sleep disturbance is often attributed to nocturnal hot flashes. These nocturnal hot flushes may be the cause of sleep disruption in many peri- and postmenopausal women. However, many of these women may also have an underlying primary sleep disorder, like restless leg syndrome or sleep apnea. Thus interventions that are intended to reduce the frequency and severity of hot flushes may not be fully effective for a significant number of women. For peri- and postmenopausal women presenting with sleep problems, clinicians must take a comprehensive sleep history to rule out a primary sleep disorder and, if necessary, obtain polysomnography to confirm the diagnosis.


Treatment for Menopausal Symptoms

magnet: How integrated should my epilepsy doctor and my PCP be when treating both of my medical conditions?

Speaker__-_Dr__Adele_Viguera: It is important to work in collaboration with your PCP and epilepsy doctor as well as your GYN, especially if you choose to be on hormonal treatment. For women with epilepsy, there is a concern that hormonal treatments may worsen seizure frequency. In some case, hormonal treatments may interfere with the metabolism of the anticonvulsant and vice versa—some anticonvulsants such as carbamazepine (Tegretol) may interfere with the metabolism of hormonal treatments (birth control pill or HRT)  For example, there is evidence that oral contraceptive pills and HRT may lower lamotrigine levels.

kathleen: Is the risk of depression greater with menopause if you have epilepsy also?

Speaker_s__-_Dr__Adele_Viguera: While the risk for depression among WWE entering menopause remains to be determined, the risk for depression among men and women with epilepsy is well established. Prevalence rates of depression among patients with epilepsy are substantially higher than in the general population, ranging from 20% to 55% in patients with recurrent seizures.

Risk factors for depression in epilepsy include female gender, family history of mood disorder, temporal and frontal lobe epilepsy frontal lobe dysfunction and complex partial seizures. Evidence also suggests that rates of depression are higher amongst refractory patients, with rates as high as 70%. In addition, patients with epilepsy are at very high risk of suicide; upwards of 10 times greater than the general population . Despite its high prevalence, depression in epilepsy remains frequently unrecognized or untreated.

caroline: I’m going through menopause and I want to use hormone replacement therapy. How will this affect my epilepsy?

Speaker__-_Dr__Adele_Viguera: Hormone replacement treatment can potentially have a negative effect on your epilepsy based on a recent study. In one study based on a patient questionnaire, WWE reported an increase in seizures with HRT use.

These preliminary findings were followed by a randomized control trial of HRT vs. placebo. Investigators found that the standard HRT therapy appeared to increase seizure frequency in a dose-related manner. In addition, the investigators also demonstrated that HRT appeared to interfere with AED metabolism, lowering lamotrigine levels. Thus, for women with epilepsy, HRT poses several risks and may not be a prudent treatment option.

nystrom: Can you discuss the hormonal and non-hormonal treatments for menopause as related to epilepsy?

Speaker__-_Dr__Adele_Viguera: Hormonal Interventions: Estrogen replacement therapy (ERT) is the gold standard and most effective treatment for hot flushes in menopausal women. ERT is almost universally effective after 3 to 4 weeks of use. ERT is also an effective treatment for sleep disruption associated with hot flushes, with profound benefits for sleep quality and improvement of sleep efficiency. ERT improves sleep efficiency and normalizes sleep architecture. ERT is also effective in treating perimenopausal depression.

However, recent reports by the Women's Health Initiative (WHI) demonstrating that long-term HRT use was associated with an increased risk for cardiovascular events and breast cancer changed the risk-benefit ratio on HRT use for millions of women. Whereas HRT was used previously for treatment of hot flushes and for prevention of cardiovascular disease and osteoporosis, the WHI reports have narrowed the primary use of HRT to short-term treatment of menopausal hot flushes and associated menopausal symptoms because long-term use of HRT has serious health risks.

newtonm: Besides sleep disturbances and mood disorders, are there any other 'quality of life' symptoms that are unique to epileptic perimenopausal or menopausal women with epilepsy?

Speaker__-_Dr__Adele_Viguera: There have not been any studies to determine other quality of life issues for women with epilepsy entering the perimenopause/menopause. Further research is needed in this area.

jnjay: How does serotonin relate to perimenopause & neurological nerve tension? How is serotonin related to menopause?

Speaker__-_Dr__Adele_Viguera: At this time we do not know if there is a clearly defined relationship between serotonin and peri or postmenopausal symptoms.  We do know that estrogen exerts generally positive effects in serotonergic neurons and on their postsynaptic targets. In animal models, estrogen treatment increases the levels of an enzyme that increases the synthesis of serotonin. In a study involving humans, investigators demonstrated that estrogen treatment increased serotonin receptors in the prefrontal cortex of postmenopausal women.


Research

sanfranmomma: Is there any clinical study looking at menopause, epilepsy and depression?

Speaker_-_Dr__Adele_Viguera: Yes, we currently are conducting a study. Despite the fact that more than one million women are expected to reach menopause each year, the relationship between menopause, epilepsy, and treatment for menopausal-related symptoms, has not been systematically investigated.  We plan to study this important issue among women with epilepsy.

Our study is called: “Citalopram versus Placebo for Symptomatic Perimenopausal and Postmenopausal Women with Epilepsy.”  The purpose of the study is to evaluate the effectiveness of Citalopram (brand name Celexa), for the treatment of depression and other menopausal symptoms among perimenopausal (before menopause) and postmenopausal (after menopause) women with epilepsy.

This research study has been approved by the Cleveland Clinic Institutional Review Board.  Our research is focused on Citalopram; an FDA approved antidepressant medication that does not have a negative effect when taken in combination with anti-epileptic drugs.

sanfranmomma: Why is this study important?

Speaker-_Dr__Adele_Viguera: No published studies to date have explored the overall benefits of using SSRI antidepressants for the treatment of menopausal women with epilepsy who present with depressive and menopause.


Closing

Cleveland_Clinic_Host: I'm sorry to say that our time with Dr. Adele Viguera is now over. Thank you again Dr. Viguera for taking the time to answer our questions about the impact of epilepsy on the quality of life during menopause today.

Speaker-_Dr__Adele_Viguera: Thank you for your participation.


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This information is provided by Cleveland Clinic as a convenience service only and is not intended to replace the medical advice of your doctor or health care provider. Please consult your health care provider for advice about a specific medical condition. Please remember that this information, in the absence of a visit with a health care professional, must be considered as an educational service only and is not designed to replace a physician's independent judgment about the appropriateness or risks of a procedure for a given patient. The views and opinions expressed by an individual in this forum are not necessarily the views of the Cleveland Clinic institution or other Cleveland Clinic physicians. ©Copyright 1995-2014. The Cleveland Clinic Foundation. All rights reserved.


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