Dr Anne Coker reviews SIGN Guideline 143 on adults with epilepsy and the recommendations for specific patient groups including people with psychiatric conditions
Read this article to learn more about:
- structured primary-care review following diagnosis of epilepsy
- epilepsy and women's health including implications during pregnancy
- psychiatric co-morbidity and mortality.
Epilepsy is a condition characterised by a tendency to have recurring unprovoked seizures and is associated with adverse impact on quality of life and increased mortality. The prevalence of epilepsy in the UK is approximately 9.7 per 1000 or 0.97% and worldwide, epilepsy affects around 50 million people, of whom 80% are in developing countries.1
Adults with epilepsy require structured annual review in primary care to discuss drug adherence, alcohol intake, lifestyle, and driving advice as well as assessment of potential comorbid depression and suicidality. 2 Seizure frequency and date of last seizure should be determined. Adults with well-controlled epilepsy frequently have no secondary care input and rely on primary care to meet these needs.
Where seizures persist despite antiepileptic drug (AED) treatment, factors relating to poor control including incorrect diagnosis of epilepsy, inappropriate choice of AED for the epilepsy syndrome, and poor adherence to prescribed AEDs should be explored and referral to an epilepsy specialist considered. 2 This facilitates access to epilepsy specialist nurse support, and where required, access to tertiary care services.
Adults with epilepsy have an increased risk of premature death in comparison to the general population. Alcohol misuse, motor vehicle accidents, drowning, suicide, and sudden unexpected death in epilepsy (SUDEP) are relevant factors contributing to premature death.2
SIGN's updated guideline on Diagnosis and management of epilepsy in adults (SIGN 143, published in May 2015)2 reflects substantial changes in epilepsy management since the previous guideline, published in 2003. It covers all aspects of diagnosis and management, including a completely revised section on epilepsy and women's health and new sections on psychiatric comorbidity, sleep, and mortality (including SUDEP).
The rate of misdiagnosis of epilepsy is high at around 25%. To reduce risk of misdiagnosis, the diagnosis of epilepsy should be made by an epilepsy specialist, ideally in the setting of a dedicated first-seizure or epilepsy clinic. The definition of an epilepsy specialist quoted in SIGN 143 is: '… a trained doctor with expertise in epilepsy as demonstrated by training and continuing education in epilepsy, peer review of practice and regular audit of diagnosis. Epilepsy must be a significant part of their clinical workload (equivalent to at least one session a week).' 2,3
The classification of epilepsy influences treatment choices, investigation, prognosis, and counselling. An updated classification and organisational system was proposed by the International League Against Epilepsy (ILAE) in 2010, although this is evolving and undergoing refinements. It is increasingly used in clinical practice, although has yet to be universally adopted. The terms 'simple partial seizure' and 'complex partial seizure' have been replaced by the term 'focal seizure'. Focal seizures in which consciousness is impaired are described as 'focal dyscognitive seizures'.
The terms 'idiopathic', 'symptomatic' and 'cryptogenic' have been replaced by the terms 'genetic', 'structural-metabolic', and 'unknown', respectively. For the purposes of this guideline, the nomenclature of the updated (ILAE 2010) classification system has been used.4
Epilepsies are broadly divided into these two categories:4
- genetic generalised epilepsies (idiopathic generalised epilepsies) usually present before the age of 25 years. They may be associated with myoclonic jerks, absences, and typical electroencephalography (EEG) changes. Triggers include sleep deprivation and alcohol
- focal epilepsies may present with focal motor activity, automatisms, déjà vu, and/or secondary generalised seizures.
Conditions most frequently confused with epilepsy include:2
- vasovagal syncope
- cardiac syncope
- non-epileptic attack disorder (alternatively known as psychogenic non-epileptic seizures, or dissociative seizures, or pseudoseizures)
- alcohol or drug-related seizures
- metabolic changes such as hypoglycaemia
- panic disorder.
Suspected first seizure or suspected new epilepsy
Patients with a suspected first seizure or new epilepsy should be advised not to drive until they have seen an epilepsy specialist. 5,6 They should be referred to a specialist in epilepsy and should be advised to take to their consultation an eyewitness (to the attack) or contact details of someone who witnessed the attack. 6 Anti-epileptic drugs (AEDs) should not be commenced in primary care without epilepsy specialist advice.
Anti-epileptic drug choices
The choice of AED is influenced by classification of the epilepsy. Anti-epileptic drugs are is initiated at a low dose and slowly titrated upwards to reach an effective therapeutic dose.2 Possible treatments include:
- genetic generalised epilepsy— sodium valproate is the most effective AED; if, however, sodium valproate is poorly tolerated or contraindicated, lamotrigine and topiramate are suitable alternatives. In women of childbearing age, levetiracetam or lamotrigine are advisable
- focal onset seizures— lamotrigine is the drug of choice for focal onset seizures but if lamotrigine is poorly tolerated, carbamazepine and levetiracetam are other options.
Practitioners should avoid switching between different manufacturers of AEDs because evidence suggests that changing formulations may jeopardise seizure control.7
Combination therapy can be considered when two first-line AEDs have failed.7
Drug-resistant epilepsy has been defined as failure to achieve sustained freedom from seizures after trials of two tolerated and appropriate AED schedules (whether as monotherapies or in combination).8 Many factors influence seizure control in patients with drug-resistant epilepsy.
If seizures persist despite good adherence to AEDs, referral to an epilepsy specialist should be considered to enable accurate classification and tailored management of the person's seizures.2
Prolonged seizures including status epilepticus2
If a seizure or series of seizures lasts for more than 5 minutes, administer buccal or intranasal midazolam 10 mg as first-line rescue medication and give oxygen. If midazolam is not available, administer rectal diazepam 10 mg. Arrange emergency patient transfer to hospital by ambulance, to facilitate further intervention including securing airway and administration of intravenous benzodiazepines.
Recurrent, prolonged, or serial seizures in the community
Patients in the community with recurrent, prolonged, or serial seizures should ideally have an individualised protocol from secondary care, providing written instructions on their management. SIGN 143 states that:2'Where a care plan is required, this should be drawn up in consultation with the GP and/or specialist, used by everyone working with the patient, and reviewed regularly. Protocols for rescue medication should be reviewed regularly and may be withdrawn or amended where such plans have not been enacted after a prolonged period.'
Withdrawal of anti-epilepsy drugs
Factors influencing a decision about whether to withdraw AEDs include considerations about driving, employment, fear of recurrent seizures or their consequences (e.g. injury or death), and concerns about prolonged AED treatment. Epilepsy prophylaxis need not be lifelong. If after 2 years' seizure freedom a patient wishes to proceed with drug withdrawal, refer them to an epilepsy specialist for an opinion and advice. 2
A survey of patients' perspectives on services for epilepsy reported that:9'... most people with epilepsy (67.6%) would prefer their care to be community based, especially older patients and patients with mild epilepsy.'
Another study revealed that 61% of patients would prefer their care to be shared between primary and secondary services.1,10 A prospective audit to measure unmet clinical needs in 388 patients receiving treatment for epilepsy found that 48% of the 62 patients with poor seizure control were not receiving shared care.11 Specialist epilepsy nurses can facilitate shared care.9 The requirement for annual structured review in primary care is unchanged from SIGN 70, based upon a UK epilepsy needs document.12 People with epilepsy who are seizure-free on AEDs and discharged from hospital review continue to have significant healthcare needs and depend upon primary care review to have these needs met.
Healthcare professionals who carry out annual primary care reviews for patients with epilepsy should have attended an epilepsy training course in the previous 5 years or be able to demonstrate equivalent experience from continuing professional development.6 Annual primary care review should be carried out face-to-face and include questions about:
- seizure frequency and date of last seizure
- to determine seizure control
- focal seizures where appropriate
- if focal seizures are overlooked there may be an erroneous impression of good control
- anti-epileptic drug dose and adherence
- poor adherence increases risk of seizures
- anti-epileptic drug adverse effects
- co-existent low mood or depression
- the suicide rate of people with epilepsy is reported to be three times higher than that of the general population2
- alcohol intake
- seek possibility of provoked seizures
- driving status
- this should be clarified because epileptic attacks are the most frequent medical cause of collapse at the wheel.5
Anti-epileptic drugs are associated with a higher risk of clinical fracture.13,14,15,16,17 Patients taking AEDs should receive dietary and lifestyle advice to minimise the risk of osteoporosis.2
Epilepsy specialist nurses and the voluntary sector
Primary care professionals at all levels should be aware of the valuable contribution that can be made by epilepsy specialist nurses and by the voluntary sector (see Box 1, below).
Box 1: Some useful sources of information2
- Provides information about coping with epilepsy and seizures and free help and advice via email and telephone helplines
- 0808 800 5050
- Epilepsy Connections was formed in April 2000 to provide information and support to people with epilepsy
- 0141 248 4125
- The UK’s leading provider of epilepsy services, with the aim of enhancing the quality of life of people affected by epilepsy by promoting research, education and public awareness, and by delivering specialist medical care and support services
- 01494 601300
- Scotland’s leading epilepsy charity campaigning for improved healthcare, better information provision, and an end to stigma
- 0141 427 4911
- This organisation provides bereavement support for relatives of people who have died from epilepsy
- 24 hour answering service: 01235 772852
- 01235 772850
UK Epilepsy and Pregnancy Register
- Provides support for pregnant women in the UK who have epilepsy
- 0800 3891248
Provision of information
SIGN 143 recommends that helpline telephone numbers and contact details of voluntary organisations should be given to all patients with epilepsy. Box 1 (above) lists organisations that offer useful information and support to patients and carers and Figure 1 (below) provides a checklist for provision of information.2
Specific patient groups with epilepsy
Specific groups of individuals with epilepsy addressed by the recommendations in SIGN 143 include:
- women of childbearing age
- people with psychiatric comorbidity
- people with learning disability
- older people.
By giving women of childbearing age who have epilepsy advice about contraception, pregnancy, and information about epilepsy, practitioners increase the likelihood that contraception will be used more reliably, health will be better during pregnancy, and pregnancy outcomes will be improved.18 Epilepsy remains one of the leading contributors to maternal mortality in the UK.19
Advice on contraception should ideally be given to young women before they become sexually active; this is described extensively in section 5 of SIGN 143; see also Figure 2 (below).
The choice of contraceptive should be carefully considered; SIGN 143 states that:2'To minimise the risk of contraceptive failure, a woman using any combined hormonal contraception, or a combined oral contraceptive pill, or a progesterone-only pill should be prescribed an antiepileptic drug that does not induce hepatic enzymes.'
Women taking hepatic enzyme-inducing drugs
Levonorgestrel intrauterine system or depot injections of progestogen can be used without restriction in women taking hepatic enzyme-inducing AEDs. Progestogen-only oral contraceptives and implants, however, are not recommended in this group of women, and if there is no alternative to prescribing the combined oral contraceptive pill (COCP), this should contain at least 50 μg daily of oestrogen and even with these measures there is a risk of pregnancy; consider 'tricycling', i.e. taking three packs of the high dose COCP consecutively and reducing the number of pill-free days to four. Enzyme induction can last for 14–18 days after withdrawal of the AED.2
Women taking lamotrigine
Women with epilepsy receiving lamotrigine can use progestogen-only contraceptives without restriction. A small study in women taking progestogen-only contraception reported a 20–100% increase in lamotrigine circulating concentrations in women receiving the AED with desogestrel.20 If these medications are prescribed together, women should be counselled about the possibility of symptoms of lamotrigine toxicity such as impaired balance, coordination, concentration, responsiveness or alertness, or symptoms of drowsiness or dizziness, or altered seizure control.
Lamotrigine is not thought to affect the efficacy of combined hormonal contraceptives. 21 Women receiving lamotrigine may have their lamotrigine levels halved after introduction of COCP. 22 This may increase risk of seizures and healthcare professionals should warn patients of the potential for reduced efficacy of lamotrigine under these circumstances and its dosing may need to be altered if these two medications are used together.2 This effect is negated when lamotrigine is prescribed with sodium valproate, which inhibits lamotrigine glucuronidation.2 If combined hormonal contraceptives are withdrawn in women taking lamotrigine, toxicity due to rising levels of the latter may occur and women should be informed of signs and symptoms of lamotrigine toxicity2 which are listed above.
Women with epilepsy who are not taking antiepileptic drugs, or who are taking non-enzyme inducing antiepileptic drugs, including lamotrigine, can use emergency contraception as for the general population. 2
Women who require emergency contraception while using an enzyme-inducing drug (or within 28 days of stopping enzyme-inducing drugs) should be advised that the copper intrauterine device (Cu-IUD) is the most effective method of emergency contraception and that it can also be used for ongoing contraception.
Women with epilepsy using enzyme-inducing drugs (or who have taken enzyme-inducing drugs within 28 days) who decline or who are not eligible to have a Cu-IUD for emergency contraception should be offered 3 mg levonorgestrel (as opposed to 1.5 mg), ideally as soon as possible, and within 72 hours of unprotected intercourse.23 NB levonorgestrel does not have marketing authorisation for this dosage. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented. See the General Medical Council’s Good practice in prescribing and managing medicines and devices for further information.24 Ulipristal acetate should be avoided in women taking hepatic enzyme-inducing AEDs because of a risk of reduced contraceptive efficacy. 23
Reliable contraception should be discussed early in the postpartum period. Progesterone-only oral contraception is contraindicated postpartum in women taking hepatic enzyme-inducing AEDs as these increase progesterone metabolism. 2,23
Before a planned pregnancy, women of childbearing age with epilepsy benefit from a specialist services review of diagnosis and to improve seizure control, discuss adherence and SUDEP risk, rationalise AED therapy, and discuss folic acid supplementation and epilepsy inheritance concerns.
The majority of women with epilepsy can be reassured that they are likely to have a normal pregnancy and delivery.25 Women who are seizure-free prior to pregnancy have increased likelihood of seizurefreedom in pregnancy.26 Good adherence to medication is advisable to reduce risk of seizures.27 Women with epilepsy on AEDs should take daily folic acid from preconception until the end of the first trimester of pregnancy to reduce the risk of major congenital malformations.2 Higher-dose folic acid, at 5 mg daily, is generally recommended for women with epilepsy receiving AEDs.28 For women with epilepsy who are not taking AEDs, 400 μg folic acid daily should be taken unless the woman has a family history of, or previous child with, a neural tube defect, or has a body mass index >30 kg/m2, when 5 mg folic acid daily should be taken.29,30,31
Sodium valproate should be avoided during pregnancy, because of a higher rate of teratogenicity compared with other AEDs; however, no AED should be discontinued during pregnancy unless this has first been discussed with an epilepsy specialist.2
Seizure control should be optimised prior to pregnancy, and pregnancies in women with epilepsy should be supervised in an obstetric clinic with access to an obstetrician with a special interest in medical disorders in pregnancy and an epilepsy specialist.2
People with psychiatric comorbidity
Major depression is the main psychiatric comorbidity in people with epilepsy with rates of 24% recorded.2,32 Suicide rates in people with epilepsy are three times higher than those in the general population. Attempts should be made to identify depression and suicidal ideation. 2,33
Psychosis in people with epilepsy can present as a chronic condition or can be episodic, with direct relationship to seizures.
Negative psychotropic effects have been associated primarily with levetiracetam, tiagabine, zonisamide, topiramate, and vigabatrin. Psychoses may occur with levetiracetam, tiagabine, topiramate, and vigabatrin. 34
People with learning disability and epilepsy
Epilepsy associated with learning disability is common with the prevalence highest (about 50%) in people with severe disability and cerebral palsy.35 People with learning disability and epilepsy should have access to the same range of investigations and treatment as the rest of the population.36,37 In adults with Down's syndrome, seizures can be a presenting symptom of dementia and over 80% of people with Down's Syndrome and dementia develop seizures. The most common type of seizures in these patients are generalised tonic-clonic seizures and myoclonic seizures although other seizure types may be seen.2
Older people with epilepsy
Epilepsy commonly presents in the older population in the Western world. The annual incidence is 85.9 per 100,000 for people aged 65–69 years and 135 per 100,000 for those aged over 85 years. 38 Older people with epilepsy have a mortality rate 2–3 times higher than the general population.2 Patients with Alzheimer's disease are up to ten times more likely to develop epilepsy than those without the condition.39,40 Stroke can account for up to 50% of cases where a cause can be identified, and the risk of epilepsy increases up to 20-fold in the first year after a stroke.39 If there are coexistent cognitive problems, an epilepsy care plan should be considered.
Sleep and epilepsy
Sleep (and sleep deprivation) can be a trigger for some epileptic seizures. Distinguishing parasomnias from nocturnal seizures can be difficult and usually requires specialist investigation. It has been suggested that people with treatment-resistant epilepsy are at increased risk of developing obstructive sleep apnoea (OSA), and that treatment of OSA with continuous positive airway pressure may improve seizure frequency. 2 Refer to specialist sleep services if obstructive sleep apnoea is clinically suspected.2
Individuals with frequent nocturnal convulsive seizures are at increased risk of SUDEP (definition in 'Mortality' section, below), with around 60% of cases of SUDEP occurring during sleep.2 Individuals with nocturnal seizures should be counselled about adherence with antiepileptic drug treatment to minimise risk of SUDEP.2
Premature death in adults with epilepsy is reportedly higher compared with the general population, with standardised mortality ratios of 3–5.2,41,42,43 Premature death in epilepsy has a wide variety of causes including falls, drowning, drug poisoning, road traffic accidents, suicide,44 and SUDEP. Sudden unexpected death in epilepsy is defined as: 45'Sudden, unexpected, witnessed or unwitnessed, non-traumatic, nondrowning death in patients with epilepsy, with or without evidence for a seizure, and excluding documented status epilepticus, in which post-mortem examination does not reveal a toxicologic or anatomic cause of death.'
SUDEP incidence is thought to be between 0.09 and 0.35/1000 patient years. 46 Generalised tonic-clonic seizures are the principal risk factor for SUDEP. 47,48,49,50,51
Healthcare professionals and patients should aspire to complete seizure freedom, where possible, to reduce the risk of SUDEP and in an effort to achieve this healthcare professionals should encourage good medicines adherence. Patients who have sustained seizures, particularly generalised tonicclonic seizures, in the past year, should be referred to a specialist in epilepsy. Counselling about the risks of SUDEP is usually the remit of secondary care.2
People with epilepsy continue to have a wide range of unmet needs in both primary and secondary care. In primary care, structured face-to-face annual review is recommended in SIGN 143 to highlight and address some of these needs. Reduction in mortality can be achieved by improvements in seizure control using a variety of means, including appropriate driving advice, encouraging improved medications adherence, early identification of suicidal ideation, and by enabling shared care for those patients with poor seizure control.
- Patients with a suspected first seizure or new epilepsy should be referred to an epilepsy specialist and advised not to drive until they have seen the specialist
- A structured management system for epilepsy should be established in primary care and include face-to-face annual review:
- annual review should include assessment of seizure control and questions about low mood, suicidality, and driving status
- Anti-epileptic drugs are associated with a greater risk of clinical fracture. Patients taking AEDs should be given diet and lifestyle advice to reduce the risk of osteoporosis
- Primary care professionals should be aware of the valuable contribution that can be made by epilepsy specialist nurses and by the voluntary sector
- To reduce the risk of SUDEP, seizure freedom is the goal where possible:
- if seizures persist despite good adherence to AEDs, referral to an epilepsy specialist should be considered to enable accurate classification and tailored management of the person’s seizures
- Seek specialist advice both for women of childbearing potential on AEDs who are planning a pregnancy and for women who are pregnant
- People with learning disability and epilepsy should have access to the same range of investigations and treatment as the rest of the population
- If seizure-free on AEDs for at least 2 years, patients should be given the opportunity to discuss possible AED withdrawal with an epilepsy specialist
- For a tonic-clonic seizure or series of seizures that last 5 minutes or longer, midazolam 10 mg given buccally or intranasally is first-line rescue medication.
AED=anti-epileptic drug; SUDEP=sudden unexpected death in epilepsy
GP commissioning messages
written by Dr David Jenner, NHS Alliance GMS contract/PBC Lead
- Commissioners should ensure that there are clear local referral pathways for patients with suspected first seizures or a new diagnosis of epilepsy so that they can see a specialist rapidly
- CCGs should:
- require specialist services to provide personalised care plans for people with epilepsy to include rescue medication and contraception for women of childbearing age
- explore innovative ways for commissioning these specialist staff to avoid expensive PbR tariff costs yet maintain close links with specialist care
- consider developing e-learning packages to support busy GPs and practice nurses in refreshing their knowledge of epilepsy and treatment of the condition
- Specialist nurses employed in community settings could help support epilepsy patients in the community and provide direct access, advice, and also training and support to primary care teams
- Local drug formularies should include special sections on the complexities of prescribing contraception to women with epilepsy; these patients might benefit from contraceptive and sexual health (CASH) clinic support.
- Joint Epilepsy Council of the UK and Ireland. Epilepsy prevalence, incidence and other statistics. Joint Epilepsy Council, 2011. Available at: www.epilepsyscotland.org.uk/pdf/Joint_Epilepsy_Council_Prevalence_and_ Incidence_September_11_(3).pdf
- Scottish Intercollegiate Guidelines Network.Diagnosis and management of epilepsy in adults. SIGN 143. Edinburgh, SIGN, 2015. Available at: www.sign.ac.uk/guidelines/fulltext/143/index.html
- Royal College of Physicians of Edinburgh.Consensus conference on better care for children and adults with epilepsy: Final consensus statement. Edinburgh: The College, 2002.
- Berg A, Berkovic S, Brodie M et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commissionon Classification and Terminology, 2005–2009. Epilepsia 2010; 51 (4): 676–685.
- Driver and Vehicle Licensing Agency. At a glance guide to the current medical standards of fitness to drive. Swansea: DVLA, 2014. Available at: www.gov.uk/government/uploads/system/uploads/attachment_data/ file/390134/aagv1.pdf.
- NHS Quality Improvement Scotland. Clinical standards. Neurological health services. NHS Quality Improvement Scotland, 2009. Available at: www. healthcareimprovementscotland.org/our_work/long_term_conditions/neurological_health_services/neurological_standards_2009.aspx
- Yamada M, Welty T. Generic substitution of antiepileptic drugs: a systematic review of prospective and retrospective studies. Ann Pharmacother 2011; 45 (11): 1406–1415.
- Kwan P, Arzimanoglou A, Berg A, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51 (6): 1069–1077.
- Poole K, Moran N, Bell G et al. Patients' perspectives on services for epilepsy: a survey of patient satisfaction, preferences and information provision in 2394 people with epilepsy. Seizure 2000; 9 (8): 551–558.
- Chappell B, Smithson W. Patient views on primary care services for epilepsy and areas where additional professional knowledge would be welcome. Seizure 1998; 7 (6): 447–457.
- Minshall I, Smith D. Unmet needs in patients with epilepsy, following audit, educational intervention and the introduction of the New General Practice Contract. Prim Health Care Res Dev 2012; 13 (1): 85–91.
- Brown S, Betts T, Crawford P et al. Epilepsy needs revisited: a revised epilepsy needs document for the UK. Seizure 1998; 7 (6): 435–446.
- Carbone L, Johnson K, Robbins J et al. Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women: findings from the women's health initiative (WHI).J Bone Miner Res 2010; 25 (4): 873–881.
- Jetté N, Lix L, Metge C et al. Association of antiepileptic drugs with nontraumatic fractures: a population-based analysis. ArchNeurol 2011; 68 (1): 107–112.
- Shiek Ahmad B, Hill K, O'Brien T et al. Falls and fractures in patients chronically treated with antiepileptic drugs. Neurology 2012; 79 (2): 145–151.
- Lee R, Lyles K, Colón-Emeric C. A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. Am JGeriatr Pharmacother 2010; 8 (1): 34–46.
- Vestergaard P. Epilepsy, osteoporosis and fracture risk—a meta-analysis. Acta Neurol Scand 2005; 112 (5): 277–286
- Betts T, Fox C. Proactive pre-conception counselling for women with epilepsy—is it effective? Seizure 1999; 8 (6): 322–327.
- Knight M, Kenyon S, Brocklehurst P et al. Saving lives, improving mothers' care. Lessons learned to inform future maternity care from the UK and Ireland confidential enquiries into maternal deaths and morbidity 2009–2012. Oxford: National Perinatal Epidemiology Unit, University of Oxford, 2014. Available at: www. npeu.ox.ac.uk/downloads/files/mbrrace-uk/ reports/Saving%20Lives%20Improving%20 Mothers%20Care%20report%202014%20 Full.pdf
- Schwenkhagen A, Stodieck S. Interaction between Lamotrigine and a progestin-only contraceptive pill containing desogestrel 75mg (Cerazette). Epilepsia 2004; 45: 144.
- Sidhu J, Job S, Singh S, Philipson R. The pharmacokinetic and pharmacodynamic consequences of the co-administration of lamotrigine and a combined oral contraceptive in healthy female subjects. Br J Clin Pharmacol 2006; 61 (2): 191–199.
- Gaffield ME, Culwell KR, Lee CR. The use of hormonal contraception among women taking anticonvulsant therapy. Contraception 2011; 83 (1): 16–29.
- Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit. Drug interactions with hormonal contraception. London:FSRH, 2012. Available at: www.fsrh.org/pdfs/CEUguidancedruginteractionshormonal.pdf
- General Medical Council. Good practice in prescribing and managing medicines and devices. London: GMC, 2013. Available at: www.gmc-uk.org/guidance/ethical_guidance/14316.asp
- Battino D, Tomson T, Bonizzoni E et al. Seizure control and treatment changes in pregnancy: observations from the EURAP epilepsy pregnancy registry. Epilepsia 2013; 54 (9): 1621–1627.
- Harden C, Hopp J, Ting T et al. Practice parameter update: management issues for women with epilepsy—focus on pregnancy (an evidence-based review): obstetrical complications and change in seizure frequency. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society.Neurology 2009; 73 (2): 126–132.
- Fairgrieve S, Jackson M, Jonas P et al. Population based, prospective study of the care of women with epilepsy in pregnancy. BMJ 2000; 321 (7262): 674–675.
- Crawford P. Best practice guidelines for the management of women with epilepsy. Epilepsia 2005; 46 (Suppl. 9): 117–124.
- Czeizel A, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. NEngl J Med 1992; 327 (26):1832–1835.
- Rasmussen S, Chu S, Kim S et al. Maternal obesity and risk of neural tube defects: a metaanalysis. Am J Obstet Gynecol 2008; 198 (6): 611–619.
- Modder J, Fitzsimons K. Management of women with obesity in pregnancy. London:Centre for Maternal and Child Enquiries and the Royal College of Obstetricians and Gynaecologists, 2010. Available at: bit.ly/1CU1frp
- Gandy M, Sharpe L, Nicholson Perry K et al. Assessing the efficacy of 2 screening measures for depression in people with epilepsy.Neurology 2012; 79 (4): 371–375.
- Christensen J, Vestergaard M, Mortensen P et al. Epilepsy and risk of suicide: a population-based case–control study. Lancet Neurol 2007;6 (8): 693–698.
- Piedad J, Rickards H, Besag F, Cavanna A. Beneficial and adverse psychotropic effects of antiepileptic drugs in patients with epilepsy: a summary of prevalence, underlying mechanisms and data limitations. CNS Drugs 2012; 26 (4): 319–335.
- Sillanpaa M. Epilepsy in the mentally retarded. In: Wallace S, editor. Epilepsy in children. London: Chapman and Hall Medical 1996; 417–427.
- Hannah J, Brodie M. Epilepsy and learning disabilities—a challenge for the next millennium? Seizure 1998; 7 (1): 3–13.
- Coulter D. Comprehensive management of epilepsy in persons with mental retardation.Epilepsia 1997; 38: S24–S31.
- Wallace H, Shorvon S, Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet 1998; 352 (9145): 1970–1973.
- Brodie MJ, Elder AT, Kwan P. Epilepsy in later life. Lancet Neurol 2009; 8 (11): 1019–1030.
- Irizarry MC, Jin S, He F, Emond JA, Raman R, Thomas RG, et al. Incidence of new-onset seizures in mild to moderate Alzheimer disease.Arch Neurol 2012; 69 (3) 368–372.
- Cockerell O, Johnson A, Sander J et al. Mortality from epilepsy: results from a prospective population-based study. Lancet 1994; 344 (8927): 918–921.
- Lhatoo S, Johnson A, Goodridge D et al. Mortality in epilepsy in the first 11 to 14 years after diagnosis: multivariate analysis of a longterm, prospective, population-based cohort.Ann Neurol 2001; 49 (3): 336–344.
- Neligan A, Bell G, Johnson A et al. The longterm risk of premature mortality in people with epilepsy. Brain 2011; 134 (Pt 2): 388–395.
- Fazel S, Wolf A, Långström N et al. Premature mortality in epilepsy and the role of psychiatric comorbidity: a total population study. Lancet 2013; 382 (9905): 1646–1654.
- Nashef L. Sudden unexpected death in epilepsy: terminology and definitions. Epilepsia 1997; 38 (11 Suppl): S6–S8.
- Tomson T, Nashef L, Ryvlin P. Sudden unexpected death in epilepsy: current knowledge and future directions. Lancet Neurol 2008; 7 (11): 1021–1031.
- Langan Y, Nashef L, Sander J. Case-control study of SUDEP. Neurology 2005; 64 (7): 1131–1133.
- Nilsson L, Farahmand BY, Persson PG, Thiblin I, Tomson T. Risk factors for sudden unexpected death in epilepsy: a case-control study. Lancet 1999; 353 (9156): 888–893.
- Walczak TS, Leppik IE, D'Amelio M, Rarick J, So E, Ahman P, et al. Incidence and risk factors in sudden unexpected death in epilepsy: a prospective cohort study. Neurology 2001; 56 (4): 519–525.
- Mohanraj R, Norrie J, Stephen L. Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study. Lancet Neurol 2006; 5 (6): 481–487.
- Hesdorffer D, Tomson T, Benn E et al. Do antiepileptic drugs or generalized tonic-clonic seizure frequency increase SUDEP risk? A combined analysis. Epilepsia 2012; 53 (2): 249–252.