• Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of epilepsy in adults. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Apr. 49 p. (SIGN publication; no. 70). [295 references]



• Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of epilepsy in adults. Update to printed guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2004 Jun 7. 3 p. [1 reference]

• Epilepsy
• Status epilepticus

Diagnosis
Management
Treatment

Critical Care
Emergency Medicine
Family Practice
Internal Medicine
Neurology
Obstetrics and Gynecology
Pediatrics

Advanced Practice Nurses
Nurses
Patients
Pharmacists
Physician Assistants
Physicians
Public Health Departments
Social Workers

To provide evidence based recommendations on the diagnosis and treatment of epilepsy, including recommendations on initial antiepileptic drug (AED) treatment, management of drug-resistant epilepsy, management of status epilepticus, management of provoked seizures, management of people with learning disability and epilepsy, and contraception, pregnancy, and menopause

Note: Epilepsy in the elderly is addressed only indirectly. Other text exists detailing the management of epilepsy in the elderly and after stroke.

Adult patients with epilepsy or status epilepticus

Diagnosis

1. Patient history, including what occurred before, during, and after the attack
2. Electroencephalography (EEG)
3. Magnetic resonance imaging (MRI)
4. Computed tomography (CT) scanning

Treatment

1. Antiepileptic drugs (AEDs), such as carbamazepine, sodium valproate, lamotrigine, and oxcarbazepine monotherapy
2. Combination therapy of AEDs
3. Short-term benzodiazepine treatment
4. Psychological treatments
5. Referral for assessment for neurosurgical treatment
6. Intravenous (IV) lorazepam or diazepam for immediate treatment of generalised tonic-clonic status epilepticus
7. Fosphenytoin with electrocardiography (ECG) monitoring or phenytoin with electrocardiography monitoring or phenobarbital for sustained control if seizures continue in generalised tonic-clonic status epilepticus
8. Rectal diazepam

Note: Liver function and full blood count should not be monitored routinely.)

Contraception, Pregnancy, and Menopause Management

1. Oral contraception with oestrogen
2. Barrier methods of contraception
3. Folic acid
4. Vitamin K₁ intramuscularly at birth for infant born to mother taking enzyme-inducing AEDs
5. Betamethasone for women taking enzyme-inducing AEDs with preterm labour threat
6. Intravenous lorazepam or diazepam for seizures during labour

Note: The progesterone-only contraceptive is not recommended for women taking enzyme-inducing AEDs.

Note: Progesterone implants are not suitable for women taking enzyme-induced AEDs.

Note: Hormone replacement therapy [HRT] should be prescribed for the same indications as in women who do not have epilepsy.

• Seizure frequency
• Seizure severity scales
• Adverse events
• Neuropsychological assessment
• Quality of life
• Seizure control
• Neurological disability
• Mortality

Hand-searches of Published Literature (Primary Sources)
Hand-searches of Published Literature (Secondary Sources)
Searches of Electronic Databases

Not stated

Weighting According to a Rating Scheme (Scheme Given)

Levels of Evidence

1++: High quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs with a very low risk of bias

1+: Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1-: Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias

2++: High quality systematic reviews of case control or cohort studies. High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal

2+: Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal

2-: Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal

3: Non-analytic studies, e.g. case reports, case series

4: Expert opinion

Systematic Review

Expert Consensus

The grade of recommendation relates to the strength of the evidence on which the recommendation is based. It does not reflect the clinical importance of the recommendation.

Grade A: At least one meta-analysis, systematic review of randomized controlled trials (RCTs), or randomized controlled trial rated as 1++ and directly applicable to the target population; or

A body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results

Grade B: A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or

Extrapolated evidence from studies rated as 1++ or 1+

Grade C: A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or

Extrapolated evidence from studies rate as 2++

Grade D: Evidence level 3 or 4; or

Extrapolated evidence from studies rated as 2+

Good Practice Points: Recommended best practice based on the clinical experience of the guideline development group.

A formal cost analysis was not performed and published cost analyses were not reviewed.

External Peer Review
Internal Peer Review

A national open meeting is the main consultative phase of the Scottish Intercollegiate Guidelines Network (SIGN) guideline development, at which the guideline development group presents their draft recommendations for the first time. The national open meeting for this guideline was held in November 2001 and was attended by around 150 representatives of all the key specialties relevant to the guideline. The draft guideline was also available on the SIGN web site for a limited period at this stage to allow those unable to attend the meeting to contribute to the development of the guideline.

The guideline was reviewed in draft form by a panel of independent expert referees, who were asked to comment primarily on the comprehensiveness and accuracy of interpretation of the evidence base supporting the recommendations in the guideline.

The guideline was then reviewed by an Editorial Group comprising relevant specialty representatives on SIGN Council, to ensure that the peer reviewers' comments had been addressed adequately and that any risk of bias in the guideline development process as a whole had been minimised.

An algorithm for treatment after first tonic-clonic seizure is provided in the original guideline document.

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Diagnosis

• Electroencephalography (EEG) is often helpful in the diagnosis and classification of epilepsy. A normal EEG does not exclude a diagnosis of epilepsy. A single routine EEG recording will show definite epileptiform abnormalities in 29-38% of adults who have epilepsy. With repeat recordings this rises to 69-77%. The sensitivity is improved by performing an EEG soon after a seizure, and by recordings with sleep or following sleep deprivation.

  In a patient in whom the clinical history suggests an epileptic seizure but is not conclusive, the prevalence of epilepsy will be high. The finding of epileptiform abnormalities is specific, and the diagnostic value of the test is good. In a patient in whom the history is typical of some other disorder, such as syncope, the prevalence of epilepsy will be low, and any epileptiform abnormalities are more likely to be incidental. The test should not be performed in this circumstance.

  EEG can aid classification of epileptic seizures and epilepsy syndromes. The finding or not of a photoparoxysmal response can allow appropriate advice to be given. If performed within the first few weeks after a first seizure, EEG has prognostic value; patients with epileptiform abnormalities are more likely to have a second attack.

• Brain imaging detects lesions in 21-37% of patients presenting with epilepsy. Such lesions require treatment in only a small minority, but their detection may have implications for future management should the epilepsy become intractable. Idiopathic generalised epilepsies are not associated with an increased prevalence of brain lesions.
• Magnetic resonance imaging (MRI) scanning is the current standard of reference in the investigation of patients with epilepsy. Routine MRI brain scanning using simple standard sequences will detect lesions (e.g., small tumours, vascular malformations and cortical dysplasia) that are not detected by computed tomography (CT) scanning. MRI carried out for the assessment of drug-resistant epilepsy requires specialised protocols and expertise (e.g., to detect hippocampal sclerosis).

Management

• Blood level monitoring should be undertaken to answer a specific clinical question; does imperfect adherence to the treatment schedule explain the poor seizure control? Specialist knowledge is required to interpret assay results as the pharmacokinetics of some AEDs are non-linear and because of the pharmacokinetic interactions that may take place. This is particularly important given the lack of a useful "target range" for the majority of AEDs.
• People with learning disability and epilepsy should have access to the same range of investigations and treatment as the rest of the population. The high prevalence of epilepsy associated with learning disability is at its greatest (about 50%) in people with severe disability and cerebral palsy. Quality of life may be affected because of injuries sustained during seizures and because of the side effects of medication. An excess mortality has also been reported. In some adults who have learning disability it may be difficult to distinguish epilepsy from psychiatric illness, emotional and behavioural outbursts. Where doubts exist, video recording of the episode may help to secure diagnosis, with appropriate consent. Clinical guidelines exist for the management of epilepsy in adults with an intellectual disability. Treatment may need to be given under the provisions of the Adults with Incapacity (Scotland) Act 2000 if the person cannot give informed consent. Seizure freedom is an appropriate endpoint for many patients with learning disability and epilepsy.
• Information about the effects of the menopause on epilepsy is limited but there is evidence to suggest that some women experience an increase in seizure frequency at this time. Hormone replacement therapy (HRT) may improve seizure control in those who previously experienced catamenial epilepsy (seizures with menstruation) but others may experience an increase in their seizure frequency on hormone replacement therapy. The benefit of hormone replacement therapy (oestrogen with or without progesterone) in reducing the risk of osteoporosis and hip fracture is well recognised. Women who have taken AEDs are known to be at increased risk of hip fractures.

Treatment

• Whether to treat a single seizure or not is largely decided by the risk of further seizures (refer to Annex 2 of the original guideline document). Estimates of recurrence risk vary. Highest recurrence rates (up to 90%) are seen in patients with epileptic discharges on EEG or congenital neurological deficits. Lowest rates (13-40%) are associated with acute symptomatic seizures (provoked) or patients with a normal EEG and no identifiable cause for seizures. Overall the risk is 30-40%; this is greatest in the first twelve months and falls to <10% after two years.

  Treatment with antiepileptic drugs (AEDs) reduces the risk of recurrence by half. Early treatment with AEDs does not appear to alter the prognosis of epilepsy, which is best predicted by the number of seizures in the first six months after diagnosis and response to first AED.

• Comparative, randomised, double-blind trials in patients with newly-diagnosed partial and generalised tonic-clonic seizures suggest similar efficacy for phenytoin, carbamazepine, sodium valproate, lamotrigine and oxcarbazepine. The newer AEDs, lamotrigine and oxcarbazepine seem to be better tolerated and may produce fewer long term side effects and adverse interactions. Sodium valproate and lamotrigine also have efficacy for absence and myoclonic seizures but lamotrigine can worsen myoclonus in some cases. Ethosuximide has been used for absence seizures in children for many decades. Lamotrigine may have advantages for adolescents, young women and the elderly because it is well tolerated, has a favourable cognitive and behavioural profile, does not induce the metabolism of lipid-soluble drugs (such as the hormonal components of the oral contraceptive agent) and does not lead to weight gain.
• Improvement in seizure control may be obtained by combining AEDs. Choice of AED combinations should be guided by side effect profile and drug interactions. There is some evidence that combining AEDs which have different mechanisms of action may enhance effectiveness e.g., lamotrigine with sodium valproate but not with carbamazepine or phenytoin.
• Emergency treatment should be sought or given by carers of people with epilepsy once a seizure has persisted, or there are serial seizures, for more than five minutes. Generalised tonic-clonic status epilepticus is a medical emergency with significant morbidity and mortality, which can often be attributed to inadequate or delayed treatment. Other types of status epilepticus (including simple partial, complex partial and absence status epilepticus) are often associated with delayed diagnosis and treatment, but have a much lower risk of morbidity. Prompt and accurate differentiation of status epilepticus from pseudo-status epilepticus and other non-epileptic disorders is crucial if inappropriate treatment and iatrogenic morbidity are to be avoided. EEG recording may be necessary to confirm the diagnosis and to assess control, when seizures are clinically subtle (e.g., in partial status, or following treatment of tonic-clonic status epilepticus).
• Intravenous lorazepam and diazepam are both effective and safe in controlling tonic-clonic status epilepticus, when administered by paramedics, prior to transport to hospital, with a trend in favour of lorazepam. Intravenous lorazepam, phenobarbital and diazepam plus phenytoin are all effective initial treatments on hospital admission, with a trend again in favour of lorazepam, which is significantly more effective than phenytoin alone. Lorazepam has the advantage over diazepam of a much shorter duration of action, but its use in the community is limited by the need for refrigerated storage. There should be a high level of awareness of the risk of respiratory depression. Additional maintenance treatment is required following initial use of either benzodiazepine. Fosphenytoin is less irritant to veins than phenytoin and can be administered more rapidly (but still needs to be given slowly).

Antiepileptic Drug Side Effects

• Antiepileptic drug (AED) side effects are common and a major cause of drug withdrawal. Most are mild but a minority can be life threatening. Accurate data on the prevalence of adverse drug reactions (ADRs) with long term AED treatment is scarce; almost all reports refer to short term clinical trials and, as experience with vigabatrin and visual field defects has shown, long term surveillance is needed to identify all ADRs. The elderly are more sensitive to AED side effects due to altered pharmacokinetics.
• Many AED side effects are dose-related and predictable. These can be minimised by gradual escalation of dose, with dose reduction if symptoms persist. Use of slow release carbamazepine can reduce peak dose-related side effects of dizziness and blurred vision.
• Idiosyncratic drug reactions usually occur in the first weeks of treatment and are potentially serious. Rash is the most common, occurring in up to 10% of patients on carbamazepine, phenytoin or lamotrigine. Most rashes are mild and resolve promptly on discontinuation of the AED, but severe cutaneous reactions are seen in up to 1:1,000 patients. This incidence is increased if the initial dose is increased rapidly.
• The life-threatening AED hypersensitivity syndrome of fever, rash, lymphadenopathy and multiorgan failure occurs in up to 4.5:10,000 patients, mostly with carbamazepine, lamotrigine or phenytoin. It is important to note that cross sensitivity occurs between these AEDs in up to 70% of patients.
• Minor blood dyscrasias are associated with many AEDs; the majority (mild leucopaenia with carbamazepine, thrombocytopaenia with valproate) require no action. Severe blood dyscrasia occurs in 6:10,000 patients but there is no evidence to suggest that routine monitoring can reduce this risk.
• Hyponatraemia (sodium <135 but usually >125 mmol/L) is seen in about 20% of patients taking carbamazepine or oxcarbazepine; it is usually well tolerated and of no significance. Elevation of liver enzymes (delta-glutamyl transferase 90%, alkaline phosphatase 30%) is seen in people taking enzyme-inducing AEDs and is usually of no clinical significance. Clinical symptoms have been shown to be more useful than routine monitoring of liver function in identifying the onset of serious ADRs.
• Acute psychotic reactions are seen occasionally with newer AEDs, particularly in those patients with a previous history of psychiatric disease; withdrawal from the drug usually results in recovery.
• Weight gain is seen with many AEDs but significant (>10% body weight) weight gain is associated particularly with valproate. Topiramate can cause weight loss.
• Sedation and dizziness are common complaints of patients starting AED therapy but usually resolve with time. Sedation may be less with the newer AEDs. Many patients on long term AED therapy report cognitive side effects but studies to confirm this have been contradictory and confounded by the effects of chronic epilepsy. Polytherapy is probably associated with more cognitive side effects than monotherapy.
• Osteopenia, osteomalacia and increased risk of hip fracture have been associated with AED use but their aetiology is likely to be multifactorial.
• AED withdrawal was associated with an increased risk of seizure recurrence, which was influenced by the duration of seizure freedom, the history of seizure types, the occurrence of one or more seizures after the start of treatment and whether one, or more than one, AED was being taken. The data from the study were used to develop a prognostic index for seizure recurrence. This has been used to calculate the risks of seizure recurrence with continued treatment or with slow AED withdrawal (Refer to tables 2 and 3 in the original guideline document). An abnormal EEG at the time of entry into the study was associated with only a small increased risk of seizure recurrence. Since this is unlikely to influence a decision about whether to withdraw AED treatment or not in adults, EEG recording is not necessary for an informed decision to be made. The higher risks of seizure recurrence with a history of myoclonus reflect the high risk of seizure recurrence following AED withdrawal in juvenile myoclonic epilepsy. The prognostic index has not been validated on an external population, and should be used with caution.
• Important factors influencing a decision about AED withdrawal in adults include driving, employment, fear of further seizures, risks of injury or death with further seizures and concerns about prolonged AED treatment. The Driver and Vehicle Licensing Agency recommends that driving should cease during the period of AED withdrawal and for six months afterwards, and for many this factor alone may lead to a decision to continue treatment.

Risks to the Fetus from Maternal Epilepsy and Antiepileptic Drugs

• Seizure frequency increases during pregnancy in between a quarter and a third of women due to a number of factors including changes in pharmacokinetics of AEDs and poor adherence to treatment because of concerns about adverse effects on the fetus.
• The long term effect of tonic-clonic seizures on the fetus is not well established although the associated hypoxia and acidosis may adversely affect the obstetric outcome, particularly if the seizures are prolonged. Risks to the woman of injury and, rarely, death in a seizure remain in pregnancy.
• Major and minor fetal malformations occur more commonly in infants exposed to AEDs during pregnancy. The overall risk of major fetal malformation in any pregnancy is approximately 2%. This increases two to three fold in women taking a single AED. Current data suggest that the risk with valproate may be higher than with carbamazepine or lamotrigine. Polytherapy, particularly with certain combinations of drugs, carries a much higher risk (up to 24% in women taking four AEDs).
• The most common major malformations associated with established AEDs are: neural tube defects (valproate 3%, carbamazepine 1%), orofacial defects, congenital heart abnormalities and hypospadias. The risk of minor malformations including hypertelorism, epicanthic folds and digital hypoplasia is increased with AED therapy in pregnancy.
• "Fetal anticonvulsant syndromes" comprising typical dysmorphic craniofacial appearances and a variety of musculoskeletal abnormalities have been described in association with AED treatment in pregnancy. Although individual drugs have been associated with specific patterns, there is overlap between them and genetic factors may influence susceptibility.
• Whether AEDs taken during pregnancy can affect the child's intellectual development is uncertain but concern about the effects of valproate on infant development has recently been raised.
• At present there is insufficient evidence on which to base advice about the risks of most of the newer AEDs (gabapentin, levetiracetam, tiagabine, topiramate, vigabatrin) in pregnancy. Current data on lamotrigine show a malformation rate of 3% (95% confidence interval 1.5-5.7).
• Many pregnancies in women with epilepsy are unplanned, very few women take folate in the correct dose at the appropriate time and advice given about malformation risk and folate is often forgotten. Women taking AEDs, particularly valproate, are at greater risk of having a child with neural tube defects (NTD) and other malformations which may be related to altered folate metabolism. It is recommended that all women should take daily folic acid from preconception and during the first trimester of pregnancy to reduce the incidence of NTD. While there is no evidence to show that folate can reduce the incidence of AED-associated malformations, current guidelines recommend that a high dose of folate, 5 mg daily, be given from pre-conception to the end of the first trimester.
• Current guidelines recommend maternal vitamin K₁ supplementation with phytomenadione 10 mg daily from 36 weeks of pregnancy for all mothers taking enzyme-inducing AEDs (refer to table 6 of the original guideline document). However, the small risk of haemorrhagic disease of the newborn is not increased in infants of mothers taking enzyme-inducing AEDs provided the infant receives 1 mg vitamin K₁ intramuscularly at birth.

Complementary Therapy for Epilepsy

Patients should be asked if they are using any complementary medicines and warned about the possibility of adverse effects. Problems may arise with the use of some herbal medicines because of interaction with prescribed medication. The potential reduction of the plasma concentrations of carbamazepine, phenobarbital and phenytoin should be noted if St John's Wort is used concomitantly. The British National Formulary advises against this. Caution is also advised in the use of evening primrose oil but the evidence for this is less robust.

Some aromatherapy preparations (e.g., hyssop, rosemary, sweet fennel, sage and wormwood) may have an alerting effect on the brain and so may exacerbate seizures.

Drugs which Exacerbate Epileptic Seizures

Drugs may occasionally precipitate seizures particularly in patients with epilepsy or other risk factors. Commonly used drugs are listed below (causality is not always certain and may be multifactorial).

Mechanisms for triggering seizures may include:

• Lowering of seizure threshold - this is usually dose/plasma concentration dependent and factors such as renal impairment (e.g., pethidine) or co-administration of interacting drugs (e.g., ciprofloxacin/theophylline) may contribute
• Decrease in antiepileptic drug (AED) levels via pharmacokinetic drug interactions (e.g., hepatic microsomal enzyme induction with rifampicin)
• Effects secondary to other medical causes precipitated by drugs e.g., drug-induced hyponatraemia or serotonin syndrome
• Individual AEDs which themselves may cause worsening of some types of seizures
• Drug withdrawal e.g., from AEDs, alcohol, benzodiazepines, barbiturates and baclofen

Drugs which May Precipitate Epileptic Seizures

Aminophylline/theophylline

Amphetamines

Analgesics e.g., tramadol

Antibiotics e.g., penicillins, cephalosporins, quinolones

Antidepressants

Anticholinergics e.g., benztropine

Anti-emetics e.g., prochlorperazine

Antipsychotics e.g., chlorpromazine

Baclofen

Bupropion [Zyban]

Cholinesterase inhibitors e.g., donepezil

Ciclosporin

Cocaine

Isoniazid

Ketamine

Lidocaine (lignocaine)

Lithium

Mefloquine

Methylene dioxymethamphetamine (ecstasy)

Non-steroidal anti-inflammatory drugs (NSAIDs) (especially in combination with quinolone antibiotics)

Opioids e.g., diamorphine, pethidine

Oral contraceptives

Vincristine

A wide variety of drugs have been reported to precipitate or potentiate seizures in patients with or without a history of epilepsy. This does not preclude their use when indicated in patients with epilepsy and supported by a risk-benefit assessment. Common examples include:

• Antidepressants, when a selective serotonin re-uptake inhibitor (SSRI, e.g. sertraline, citalopram) may be a reasonable choice
• Antipsychotics, when drugs with lower seizure risk such as haloperidol, risperidone, sulpiride should be used in preference to drugs thought to have higher risk such as clozapine and chlorpromazine
• Antimalarials, when chloroquine and mefloquine are unsuitable for malaria prophylaxis. The current guidelines from the Malaria Reference Laboratory (included in the British National Formulary) should be consulted to choose an appropriate alternative.

• This guideline is not intended to be construed or to serve as a standard of medical care. Standards of care are determined on the basis of all clinical data available for an individual case and are subject to change as scientific knowledge and technology advance and patterns of care evolve. These parameters of practice should be considered guidelines only. Adherence to them will not ensure a successful outcome in every case, nor should they be construed as including all proper methods of care or excluding other acceptable methods of care aimed at the same results.
• The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor, following discussion of the options with the patient, in light of the diagnostic and treatment choices available. However, it is advised that significant departures from the national guideline or any local guidelines derived from it should be fully documented in the patient's case notes at the time the relevant decision is taken.

Implementation of national clinical guidelines is the responsibility of local National Health Service (NHS) organisations and is an essential part of clinical governance. It is acknowledged that not every guideline can be implemented immediately on publication, but mechanisms should be in place to ensure that the care provided is reviewed against the guideline recommendations and the reasons for any differences assessed and, where appropriate, addressed. These discussions should involve both clinical staff and management. Local arrangements may then be made to implement the national guideline in individual hospitals, units and practices, and to monitor compliance. This may be done by a variety of means including patient-specific reminders, continuing education and training, and clinical audit. Managed clinical Networks for epilepsy are being developed.

Key points for audit are identified in the original guideline document.

Living with Illness

Effectiveness
Patient-centeredness

• Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of epilepsy in adults. A national clinical guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2003 Apr. 49 p. (SIGN publication; no. 70). [295 references]



• Scottish Intercollegiate Guidelines Network (SIGN). Diagnosis and management of epilepsy in adults. Update to printed guideline. Edinburgh (Scotland): Scottish Intercollegiate Guidelines Network (SIGN); 2004 Jun 7. 3 p. [1 reference]

Not applicable: The guideline was not adapted from another source.

2003 Apr (addendum released 2004 Jun 7)

Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]

Scottish Executive Health Department

Not stated

Guideline Development Group: Dr Richard Roberts (Chairman); Dr Maria Elena Farrugia (Secretary); Ms Sheena Bevan; Professor Martin Brodie; Ms Eleanor Caldwell; Ms Francesca Chappell; Dr Roger Cull; Dr Duncan Davidson; Dr Rod Duncan; Dr Ali El-Ghorr; Dr Janet Fitton; Dr Linda Gerrie; Dr Rod Gibson; Dr Ruth Gillham; Dr Margaret Jackson; Dr Stewart Jarvie; Ms Hilary Mounfield; Ms Fiona Needleman; Ms Angela Norman; Dr Anne O'Hare; Dr Mary O'Regan; Dr Andrew Orr; Dr Puline Robertson; Dr Norman Smith; Dr Linda Stephen

All members of the Scottish Intercollegiate Guidelines Network (SIGN) guideline development groups are required to complete a declaration of interests, both personal and non-personal. A personal interest involves payment to the individual concerned, e.g., consultancies or other fee-paid work commissioned by or shareholdings in the pharmaceutical industry; a non-personal interest involves payment which benefits any group, unit or department for which the individual is responsible, e.g., endowed fellowships or other pharmaceutical industry support. SIGN guideline group members should be able to act as independently of external commercial influences as possible, therefore, individuals who declare considerable personal interests may be asked to withdraw from the group. Details of the declarations of interest of any guideline development group member(s) are available from the SIGN executive.

This summary was completed by ECRI on November 20, 2003. The information was verified by the guideline developer on January 16, 2004. This NGC summary was updated by ECRI on September 28, 2004. The information was verified by the guideline developer on January 26, 2005. This summary was updated by ECRI on April 21, 2005 following the release of a public health advisory from the U.S. Food and Drug Administration (FDA) regarding Trileptal (oxcarbazepine). This summary was updated by ECRI on November 16, 2006, following the FDA advisory on Lamictal (lamotrigine). This summary was updated by ECRI Institute on October 2, 2007, following the U.S. Food and Drug Administration (FDA) advisory on Haloperidol. This summary was updated by ECRI Institute on January 10, 2008, following the U.S. Food and Drug Administration advisory on Carbamazepine.