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Al-Faraj AO, Pang TD. Breastfeeding recommendations for women taking anti-seizure medications. Epilepsy Behav 2022; 136:108769. [PMID: 35690572 DOI: 10.1016/j.yebeh.2022.108769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 05/13/2022] [Accepted: 05/23/2022] [Indexed: 12/14/2022]
Abstract
The literature regarding breastfeeding and effects of anti-seizure medication (ASM) exposure on the breastfed infant has been evolving rapidly over the last decade as new studies advance our understanding of the extent of medication exposure via breastfeeding and the long-term developmental outcomes of breastfed infants. Currently, strong evidence supports the safety of breastfeeding for women with epilepsy (WWE) taking most prescribed ASMs. In this review, we present a comprehensive overview of the data regarding ASM exposure in breastfed infants and neurodevelopmental outcomes in breastfed infants of mothers taking various ASMs. In addition, we present current breastfeeding recommendations and the reported adverse effects of various ASMs to facilitate decision making in the clinical care of WWE.
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Affiliation(s)
- Abrar O Al-Faraj
- Boston Medical Center, Boston University School of Medicine, United States.
| | - Trudy D Pang
- Beth Israel Deaconess Medical Center, Harvard Medical School, United States.
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Vajda FJE, O'Brien TJ, Graham JE, Hitchcock AE, Perucca P, Lander CM, Eadie MJ. Achieving neurologically desirable outcomes to pregnancy in women with epilepsy. Epilepsy Behav 2022; 129:108602. [PMID: 35176651 DOI: 10.1016/j.yebeh.2022.108602] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/25/2022] [Accepted: 01/25/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVES To investigate possible factors that influenced whether pregnancy in women with epilepsy resulted in the desirable outcome of a live-born non-malformed infant and a mother whose pregnancy had been seizure free. RESULTS The desirable outcome, as defined, occurred in 46.3% of unselected pregnancies in the database of the Australian Register of Antiepileptic Drugs in Pregnancy (APR). The only factor investigated that had a statistically significant (P < 0.05) effect, increasing the chance of such a desirable outcome, was freedom from seizures in the pre-pregnancy year. However, anti-seizure medication (ASM) doses, particularly valproate doses, had been reduced prior to 15.6% of the pregnancies, and this may have concealed factors that otherwise may have adversely affected the desirable outcome rate. Analysis of data for monotherapy with the more commonly used ASMs appears to suggest that employing levetiracetam at the outset of antiseizure therapy may offer a better chance of a desirable outcome to future pregnancies than monotherapy with other ASMs, but this finding is not confirmed statistically. CONCLUSIONS In pregnancies where valproate use has already been minimized, seizure control throughout the pre-pregnancy year was associated with the best chance of a desirable outcome, as defined above. In most Australian women starting therapy for epilepsy initiating treatment with levetiracetam monotherapy may offer the best chance of such a desirable outcome to a future pregnancy, yet to be confirmed.
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Affiliation(s)
- Frank J E Vajda
- Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia; Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia.
| | - Terence J O'Brien
- Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia.
| | - Janet E Graham
- Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia.
| | - Alison E Hitchcock
- Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia.
| | - Piero Perucca
- Departments of Medicine and Neurosciences, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria 3050, Australia; Department of Neuroscience, Monash University, Melbourne, VIC 3004, Australia; Department of Neurology, Alfred Health, Melbourne, VIC 3004, Australia; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, VIC 3084, Australia; Comprehensive Epilepsy Program, Austin Health, Heidelberg, VIC 3084, Australia.
| | - Cecilie M Lander
- Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD 4027, Australia.
| | - Mervyn J Eadie
- Royal Brisbane and Women's Hospital and School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD 4027, Australia.
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Eadie MJ. Pregnancy and the Control of Epileptic Seizures: A Review. Neurol Ther 2021; 10:455-468. [PMID: 33988822 PMCID: PMC8571455 DOI: 10.1007/s40120-021-00252-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 04/15/2021] [Indexed: 10/27/2022] Open
Abstract
Over the past 50 years, published studies have provided quantitative data on the control of epileptic seizures during pregnancy. The studies have varied in quality, and particularly in the ways in which seizure control has been assessed. However, most studies have shown that seizure occurrence rates are more likely to worsen than improve during pregnancy, though in most pregnancies the rates have been unaltered. Nearly all of the studies have involved women with antiseizure medication-treated epilepsy, but there is a little evidence that seizure control also tends to worsen in pregnancies of women with untreated epilepsy. The factors likely to contribute to the seizure worsening are (i) patient non-compliance, (ii) increased antiseizure medication clearance during pregnancy resulting in lower circulating drug concentrations relative to dose, (iii) the effects of the higher female sex hormone levels during pregnancy, oestrogens being pro-epileptogenic and progesterone anti-epileptogenic, and (iv) reluctance to use the potential teratogen valproate in women capable of pregnancy, depriving them of the most effective drug for certain types of epilepsy. Compliance can be encouraged, but at the present time only one other factor is readily correctable, i.e. the increased drug clearance. This can be compensated for by raising antiseizure medication dosage during pregnancy, guided by measurement of circulating drug concentrations. This course of action appears to reduce the chance of seizure disorder worsening during pregnancy, but so far it has not provided a complete solution to the issue.
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Affiliation(s)
- Mervyn J Eadie
- School of Medicine and Biomedical Science, University of Queensland, Brisbane, QLD, 4027, Australia.
- , 4th Floor, Ladhope Chambers, 131 Wickham Terrace, Brisbane, 4000, Australia.
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Abstract
During pregnancy, there are several physiological changes during each trimester that can affect the absorption, distribution, metabolism, and elimination of drugs. Although there is a potential need to understand the pharmacokinetics and pharmacodynamics of drugs in pregnant patients, therapeutic drug monitoring is not well established for various drug classes due to ethical and safety concerns regarding the neonate. Potential risks from in utero drug exposure to the fetus may impact growth and development and may cause malformations or teratogenesis. The clinician must consider the benefits of drug treatment for the pregnant mother versus the risk to the fetus, before prescribing medications during pregnancy. The objective of this review is to aid clinicians, pharmacists, and laboratorians in understanding the pharmacokinetic and pharmacodynamic changes during pregnancy, to provide drug class recommendations for monitoring therapy throughout pregnancy via therapeutic drug monitoring, and to highlight the recent directives of governing agencies on maternal and fetal health.
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Kacirova I, Grundmann M, Brozmanova H. Therapeutic monitoring of carbamazepine and its active metabolite during the 1st postnatal month: Influence of drug interactions. Biomed Pharmacother 2021; 137:111412. [PMID: 33761618 DOI: 10.1016/j.biopha.2021.111412] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2020] [Revised: 02/02/2021] [Accepted: 02/16/2021] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVE To receive information about carbamazepine and its active metabolite 10,11-epoxide transport into mature milk and suckling infants. METHODS In this cohort study, maternal serum, mature milk, and infant serum carbamazepine and epoxide levels were measured between the 6th and 29th postnatal day (carbamazepine in 1990-2017, epoxide in 1997-2017). Paired maternal serum, infant serum and milk levels were used for the assessment of ratios of this levels. The influence of combined treatment with enzyme-inducing antiepileptic drugs and valproic acid was assessed. Relationship between maternal serum, infant serum, and milk levels was also evaluated. RESULTS Maternal carbamazepine levels were 1.4-10.4 mg/L, milk 0.5-6.7 mg/L and infant 0.5-2.6 mg/L. Maternal 10,11-epoxide levels were 0.3-5.4 mg/L, milk 0.3-3.7 mg/L and infant 0.3-0.6 mg/L. Highly significant correlations were observed exclusively between milk and maternal serum levels of both carbamazepine and 10,11-epoxide. Concomitant administration of enzyme-inducing antiepileptic drugs significantly increased the maternal apparent oral clearance of carbamazepine by approximately 130%. Carbamazepine combined with valproic acid significantly increased epoxide levels in milk and maternal serum but not in breastfed infants. CONCLUSIONS In breastfed infants, carbamazepine levels did not reach the lower limit of the therapeutic range used for the general epileptic population, and the majority of epoxide levels were less than the lower limit of quantification. Routine monitoring of carbamazepine in these infants is not compulsory. However, observation of breastfed infants is desirable. If signs of potential adverse reactions are evident, infant serum concentrations should be monitor.
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Affiliation(s)
- Ivana Kacirova
- Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic; Department of Clinical Pharmacology, Department of Laboratory Medicine, University Hospital Ostrava, 17. listopadu 1790, 700 30 Ostrava, Czech Republic
| | - Milan Grundmann
- Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic.
| | - Hana Brozmanova
- Department of Clinical Pharmacology, Faculty of Medicine, University of Ostrava, Syllabova 19, 703 00 Ostrava, Czech Republic; Department of Clinical Pharmacology, Department of Laboratory Medicine, University Hospital Ostrava, 17. listopadu 1790, 700 30 Ostrava, Czech Republic
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Betcher HK, Wisner KL. Psychotropic Treatment During Pregnancy: Research Synthesis and Clinical Care Principles. J Womens Health (Larchmt) 2019; 29:310-318. [PMID: 31800350 DOI: 10.1089/jwh.2019.7781] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Background: Psychiatric illnesses are common in women of childbearing age. The perinatal period is a particularly high-risk time for depression, bipolar, and anxiety disorders. Methods: The scope of the public health problem of perinatal mental disorders is discussed followed by an examination of the specific research methods utilized for the study of birth and developmental outcomes associated with maternal mental illness and its treatment. The evidence on exposure to common psychotropics during pregnancy and breastfeeding is reviewed. Results: Selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitor medications are not associated with higher rates of birth defects or long-term changes in mental development after adjustment for confounding factors associated with underlying psychiatric illness. Lithium exposure is associated with an increased risk for fetal cardiac malformations, but this risk is lower than previously thought (absolute risk of Ebstein's anomaly 6/1,000). Antipsychotics, other than risperidone and potentially paliperidone, have not been associated with an increase in birth defects; olanzapine and quetiapine have been linked with an elevated risk of gestational diabetes. Due to the dramatic physiological changes of pregnancy and enhanced hepatic metabolism, drug doses may need to be adjusted during pregnancy to sustain efficacy. Untreated maternal psychiatric illness also carries substantial risks for the mother, fetus, infant, and family. Conclusions: The goal of perinatal mental health treatment is to optimally provide pharmacotherapy to mitigate the somatic and psychosocial burdens of maternal psychiatric disorders. Regular symptom monitoring during pregnancy and postpartum and medication dose adjustments to sustain efficacy constitutes good practice.
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Affiliation(s)
- Hannah K Betcher
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota
| | - Katherine L Wisner
- Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.,Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
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Valproic acid concentrations in nursing mothers, mature milk, and breastfed infants in monotherapy and combination therapy. Epilepsy Behav 2019; 95:112-116. [PMID: 31035102 DOI: 10.1016/j.yebeh.2019.04.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 04/01/2019] [Accepted: 04/02/2019] [Indexed: 12/29/2022]
Abstract
Valproic acid (VPA) is currently one of the four most often prescribed antiepileptic drugs (AEDs) in pregnancy. However, only a small number of studies have measured suckling infant serum levels of the drug. We studied the transport of VPA from breastfeeding mothers to the mature milk and breastfed infants and the influence of comedication with enzyme-inducing AEDs. The data of 30 nursing women treated by VPA were analyzed retrospectively. Mature milk, maternal, and infant serum levels were collected between the 6th and 32nd postnatal day and measured by gas chromatography during the years 1996-2017. Valproic acid levels varied from 5.4 to 69.0 mg/L (mean: 39.0 ± 16.1 mg/L) in the maternal serum, from <1.0 to 16.7 mg/L (mean: 1.6 ± 3.9 mg/L) in the milk, and from <1.0 to 17.5 mg/L (mean: 4.2 ± 4.3 mg/L) in the infant serum. The milk/maternal serum level ratio ranged from <0.03 to 0.25 (mean: 0.03 ± 0.06) and the infant/maternal serum level ratio from <0.03 to 0.61 (mean: 0.11 ± 0.13). Sixty-seven percent of milk and 33% of infant VPA concentrations were below the limit of quantification. No correlations were observed between maternal serum and milk levels or between maternal and infant serum levels. In conclusion, none of the milk or infant serum VPA levels reached the lower limit of the reference range used for the general population with epilepsy, so the degree of VPA exposure in breastfed infants is less than during gestation. Nevertheless, if signs of potential adverse reactions manifest, infant serum concentrations should be measured.
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A Short Communication: Lamotrigine Levels in Milk, Mothers, and Breastfed Infants During the First Postnatal Month. Ther Drug Monit 2019; 41:401-404. [PMID: 30688868 DOI: 10.1097/ftd.0000000000000604] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Lamotrigine has become the most frequently prescribed drug in the treatment of pregnant women with epilepsy. Although some relevant studies have found a wide milk/maternal serum as well as infant/maternal serum concentration ratio, different infant ages at the time of sampling and small number of patients preclude comparison. The aim of this study was to provide a consistent evaluation. METHODS Data of 43 nursing women treated by lamotrigine were evaluated retrospectively. The authors followed the transport of lamotrigine during the first postnatal month from mothers to breastfed infants through maternal milk between the years 2002 and 2017. RESULTS Lamotrigine concentrations varied from 1.1 to 14.9 mg/L in the maternal serum, from <0.66 to 9.1 mg/L in the milk and between <0.66 and 6.9 mg/L in the infant serum. The milk/maternal serum concentration ratio ranged from <0.18 to 0.74 and the infant/maternal serum concentration ratio measured between <0.15 and 0.74. Highly significant correlations were found between milk and maternal serum levels and between infant serum levels and milk, maternal serum levels, lamotrigine daily dose, and also maternal dose related to the body weight. CONCLUSIONS The authors confirmed the wide range of the milk/maternal serum concentration ratio and the infant/maternal serum concentration ratio. Although the degree of lamotrigine exposure to the breastfed infants was smaller than during gestation, 16% of the infant serum levels measured were within the therapeutic range used for the general epileptic population. Lamotrigine concentration monitoring in breastfed infant, in our opinion, is the most relevant aspect for the analysis of actual lamotrigine exposure in infants, especially in those with clinical symptoms.
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Shawahna R. Which information on women's issues in epilepsy does a community pharmacist need to know? A Delphi consensus study. Epilepsy Behav 2017; 77:79-89. [PMID: 29127865 DOI: 10.1016/j.yebeh.2017.09.026] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 09/08/2017] [Accepted: 09/22/2017] [Indexed: 12/15/2022]
Abstract
OBJECTIVE The aim of this study was to develop and achieve consensus on a core list of important knowledge items that community pharmacists should know on women's issues in epilepsy. METHODS This was a consensual study using a modified Delphi technique. Knowledge items were collected from the literature and from nine key contacts who were interviewed on their views on what information community pharmacists should have on women's issues in epilepsy. More knowledge items were suggested by five researchers with interest in women's issues who were contacted to rate and comment on the knowledge items collected. Two iterative Delphi rounds were conducted among a panel of pharmacists (n=30) to achieve consensus on the knowledge items to be included in the core list. Ten panelists ranked the knowledge items by their importance using the Analytical Hierarchy Process (AHP). RESULTS Consensus was achieved to include 68 knowledge under 13 categories in the final core list. Items ranked by their importance were related to the following: teratogenicity (10.3%), effect of pregnancy on epilepsy (7.4%), preconception counseling (10.3%), bone health (5.9%), catamenial epilepsy (7.4%), menopause and hormonal replacement therapy (2.9%), contraception (14.7%), menstrual disorders and infertility (8.8%), eclampsia (2.9%), breastfeeding (4.4%), folic acid and vitamin K (5.9%), counseling on general issues (14.7%), and sexuality (4.4%). CONCLUSION Using consensual knowledge lists might promote congruence in educating and/or training community pharmacists on women's issues in epilepsy. Future studies are needed to investigate if such lists can improve health services provided to women with epilepsy (WWE).
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Affiliation(s)
- Ramzi Shawahna
- Department of Physiology, Pharmacology and Toxicology, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine; An-Najah BioSciences Unit, Centre for Poisons Control, Chemical and Biological Analyses, An-Najah National University, Nablus, Palestine.
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Hogan CS, Freeman MP. Adverse Effects in the Pharmacologic Management of Bipolar Disorder During Pregnancy. Psychiatr Clin North Am 2016; 39:465-75. [PMID: 27514299 DOI: 10.1016/j.psc.2016.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Management of bipolar disorder during pregnancy often involves medications with potential adverse effects, including risks to the mother and fetus. Although some specifics are known, many medications continue to have incompletely characterized reproductive safety profiles. Women with bipolar disorder who are planning pregnancy face challenging decisions about their treatment; careful risk-benefit discussions are necessary. With the goal of further informing these discussions, this article reviews the data currently available regarding medication safety in the management of bipolar disorder during pregnancy, with specific attention to lithium, valproic acid, lamotrigine, carbamazepine, and antipsychotic medications.
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Affiliation(s)
- Charlotte S Hogan
- Department of Psychiatry, Massachusetts General Hospital, Warren 605, 55 Fruit Street, Boston, MA 02114, USA
| | - Marlene P Freeman
- Department of Psychiatry, Massachusetts General Hospital, Simches 2, 185 Cambridge Street, Boston, MA 02114, USA.
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Ahmadzai H, Tee LBG, Crowe A. Pharmacological role of efflux transporters: Clinical implications for medication use during breastfeeding. World J Pharmacol 2014; 3:153-161. [DOI: 10.5497/wjp.v3.i4.153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2014] [Revised: 09/03/2014] [Accepted: 09/24/2014] [Indexed: 02/06/2023] Open
Abstract
The World Health Organisation recommends exclusive breastfeeding for the first six months of an infant’s life and in combination with solid food thereafter. This recommendation was introduced based on research showing numerous health benefits of breastfeeding for both the mother and the infant. However, there is always concern regarding the transfer of medications from mother to their breastfed baby via milk. Pharmacokinetic properties of a drug are usually used to predict its transferability into breast milk. Although most drugs are compatible with breastfeeding, cases of toxic drug exposure have been reported. This is thought to be due to active transport mechanisms whereby efflux transporter proteins expressed in the epithelial cells of the mammary gland actively secrete drugs into milk. An example of such efflux transporters including the breast cancer resistance protein which is strongly induced during lactation and this could result in contamination of milk with the substrates of this transporter which may place the suckling infant at risk of toxicity. Furthermore, there is little known about the substrate specificity of most efflux transporters as we have highlighted in this review. There also exists some degree of contradiction between in vivo and in vitro studies which makes it difficult to conclusively predict outcomes and drug-drug interactions.
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Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL. Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry 2013; 170:1240-7. [PMID: 24185239 PMCID: PMC4154145 DOI: 10.1176/appi.ajp.2013.13010006] [Citation(s) in RCA: 134] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE Little information is available on the need for dosage changes for lamotrigine in pregnant women with bipolar disorder. The authors present new data on serial serum levels of lamotrigine in pregnant patients on lamotrigine monotherapy. They also review the epilepsy literature on use of lamotrigine during pregnancy. METHOD Lamotrigine serum samples were obtained from eight mother-infant pairs at different time points during pregnancy and the postpartum period. RESULTS All of the women were taking lamotrigine throughout pregnancy. Serum-level-to-dose ratios were lower during pregnancy than the postpartum period. Lamotrigine was taken once daily in doses ranging from 100 mg to 300 mg. Three patients had an increase of 50 mg to their daily dose across pregnancy. The change in serum lamotrigine levels in the postpartum period ranged from a 30% decrease to a 640% increase compared with the first level obtained during pregnancy. Level-to-dose ratios obtained within 4 weeks after delivery reflected a mean level 402% greater than the baseline level during gestation. Compared with the third trimester, lamotrigine serum concentration increased an average of 154% within 5 weeks after delivery. The most dramatic increase in lamotrigine serum level early after delivery occurred at 1.5 weeks. The mean infant cord level was 66% of the maternal serum level at delivery. The mean breast-fed infant serum level was 32.5% of the maternal serum levels. CONCLUSIONS The pattern of lamotrigine changes during pregnancy in these women with bipolar disorder was consistent with that described in the epilepsy literature.
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Pedroviejo V, Ayuso M, Jiménez A. [Anesthesia for procedures other than neurosurgery in the adult with epilepsy]. REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION 2009; 56:425-435. [PMID: 19856689 DOI: 10.1016/s0034-9356(09)70423-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
Abstract
Epilepsy is a common disease affecting between 1% and 2% of the general population. The incidence increases with age. Given the complicated etiology and pathogenesis of this disease, epileptic patients of all ages may require anesthesia. The perioperative care of these patients involves a number of special considerations, although the main issues to deal with are pharmacologic. This review gives an overview of the etiopathogenesis and pathophysiology of epilepsy and describes the general characteristics of antiepileptic drug therapy. The anesthetic implications of chronic treatment with antiepileptic agents and the interactions between these drugs and common anesthetics are discussed in more detail.
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Affiliation(s)
- V Pedroviejo
- Servicio de Anestesiología, Reanimación y Tratamiento del Dolor, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid.
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Abstract
While most women with epilepsy can expect a normal pregnancy outcome, epilepsy remains a significant contributor to both maternal and perinatal morbidity. Pre-pregnancy planning must address reliable contraception and optimisation of antiepileptic drug (AED) regimens to minimise teratogenic risk while maintaining seizure control. The most recent data from the AED registries regarding malformations is presented in this review, as is the limited data on the newer AEDs and studies linking neurocognitive outcomes to AED exposure. During pregnancy, important considerations include; therapeutic drug monitoring, surveillance for obstetric complications and vigilance for seizures during the intrapartum and postpartum period.
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Affiliation(s)
- S P Walker
- Department of Perinatal Medicine, Mercy Hospital for Women, Heidelberg, Vic., Australia.
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Pennell PB, Thompson P. Gender-specific psychosocial impact of living with epilepsy. Epilepsy Behav 2009; 15 Suppl 1:S20-5. [PMID: 19303945 DOI: 10.1016/j.yebeh.2009.03.022] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2009] [Accepted: 03/05/2009] [Indexed: 12/29/2022]
Abstract
Although many psychosocial issues affect all people living with epilepsy, certain issues either are specific to one gender or have a different prevalence or significance between men and women with epilepsy. Most studies suggest that the incidence of epilepsy is slightly higher in males with epilepsy. Sexual dysfunction is common among men and women with epilepsy and has been related to epilepsy type and treatment. Women living with epilepsy are often prone to increased seizure frequency at certain phases of their menstrual cycles. Hormone replacement therapy in postmenopausal women may worsen seizures. Treatment during pregnancy is often a precarious balancing act between the teratogenic risks of AEDs and the maintenance of maternal seizure control. However, pregnancy registries and other prospective studies have given us invaluable information on how to optimize treatment regimens as well as information about safety of breastfeeding. These gender-specific factors should be a key consideration when counseling and treating patients with epilepsy.
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Affiliation(s)
- Page B Pennell
- Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, Suite 6000, Atlanta, GA 30322, USA.
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Pennell PB. PRACTICE ISSUES IN NEUROLOGY. Continuum (Minneap Minn) 2009. [DOI: 10.1212/01.con.0000300034.55189.2b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Abstract
Most infants born to women with epilepsy are healthy, but there are increased risks related to in utero antiepileptic drug (AED) exposure and seizures. Emerging data from pregnancy registries and other studies allow us to better balance the anatomic teratogenic and neurodevelopmental effects of AEDs against the need to maintain maternal seizure control. Several large prospective pregnancy registries demonstrate a consistent pattern of increased risk for major congenital malformations (MCMs) with valproate (VPA) use as monotherapy, compared to nonexposed populations and to other AEDs used in monotherapy. AED polytherapy likely increases risk for MCMs, but the risk is more pronounced if VPA is included. Reduced cognitive outcomes have been reported with AED polytherapy, and with use of VPA, phenobarbital (PB), and PHT as monotherapy. Dose-dependent risk has been demonstrated with VPA for MCMs and cognitive consequences. CBZ groups show normal neurodevelopment. Increased clearance of most of the AEDs occurs during pregnancy. Use of therapeutic drug monitoring during pregnancy with LTG reduces the risk for seizure worsening. The consistent findings of increased teratogenic risk for VPA should discourage use of this medication as first-line treatment in women of childbearing age.
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Affiliation(s)
- Page B Pennell
- Department of Nuerology, Emory Epilepsy Program, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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Abstract
Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) has made it possible to study the individual variations in drug utilization, to reveal noncompliance in patients and for quality assurance aspects. Even if there is a shortage of data from randomized controlled studies concerning the effectiveness of using TDM as an aid to dosage adjustment, experience from nonrandomized investigations and long-lasting clinical experience have shown that TDM of both older and newer AEDs may be of clinical benefit if used appropriately. The main situations for TDM include: after starting treatment to provide a baseline steady-state concentration for further evaluation of an individual therapeutic concentration; after change in drug dosage, in particular when nonlinear kinetics apply; at therapeutic failure to sort out a pharmacokinetic explanation for uncontrolled seizures or side effects; in case of drug interactions; and when pharmacokinetic changes due to physiological or pathological changes are foreseen (e.g., age-dependent conditions [children, elderly], pregnancy, hepatic disease, renal disease or gastrointestinal conditions potentially affecting drug absorption) and change in drug formulation (brand name/generic). Recently, new terminology and definitions have been suggested by the International League Against Epilepsy. The reference range is a range of drug concentrations quoted by laboratories and is not a therapeutic range. Emphasis should be placed on the concept of an individual therapeutic concentration.
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Affiliation(s)
- Svein I Johannessen
- The National Center for Epilepsy, Sandvika, Division of Clinical Neuroscience, Rikshospitalet University Hospital, Oslo, POB 53, N-1306 BPT, Norway.
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19
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Affiliation(s)
- Jacqueline A French
- Department of Neurology, New York University School of Medicine, New York, USA.
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20
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Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiol Drug Saf 2008. [PMID: 18533281 PMCID: PMC7167700 DOI: 10.1002/pds.1487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety. Each bibliography is divided into 20 sections: 1 Reviews; 2 General; 3 Anti‐infective Agents; 4 Cardiovascular System Agents; 5 CNS Depressive Agents; 6 Non‐steroidal Anti‐inflammatory Agents; 7 CNS Agents; 8 Anti‐neoplastic Agents; 9 Haematological Agents; 10 Neuroregulator‐Blocking Agents; 11 Dermatological Agents; 12 Immunosuppressive Agents; 13 Autonomic Agents; 14 Respiratory System Agents; 15 Neuromuscular Agents; 16 Reproductive System Agents; 17 Gastrointestinal System Agents; 18 Anti‐inflammatory Agents ‐ Steroidal; 19 Teratogens/fetal exposure; 20 Others. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.
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