3.1 When and by whom should antiepileptic drug treatment be commenced?

The crucial decision whether or not to start antiepileptic drug (AED) treatment must take into account the relative risks of recurrent seizures (including the small but important risk of sudden unexplained death in epilepsy) and the commitment to long term medication with potential side effects.

3.1.1 EPILEPSY

Antiepileptic drugs should not be given until the diagnosis of epilepsy has been confirmed (see Section 2). If there is uncertainty, a period of observation will usually clarify the epilepsy syndrome and confirm the need for treatment.^{5, 6}

3.1.2 SINGLE SEIZURES

A detailed history should be taken to exclude previous myoclonic, absence or partial seizures as patients with undiagnosed epilepsy may present with a single generalised tonic-clonic seizure.¹⁰ Evidence level 1+,2++,2+,4

Whether to treat a single seizure or not is largely decided by the risk of further seizures (see Annex 2). 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.^{38, 63, 64, 65} Overall the risk is 30-40%;⁶⁶ this is greatest in the first twelve months and falls to <10% after two years.⁶⁷ Evidence level 1+,2++,2+,4

Treatment with AEDs reduces the risk of recurrence by half.^{68, 69} 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.^{70, 71, 72} Evidence level 1+,2++,2+,4

The patient’s view on medication should be considered. Women planning a pregnancy may choose to avoid AEDs in the short term, though they must be warned of the attendant risks (see Section 4.3). Individuals wishing to avoid recurrent seizures, eg for driving, should be offered immediate treatment.

The decision to start antiepileptic drugs (AEDs) should be made by the patient and an epilepsy specialist.

AEDs should be offered after a first tonic-clonic seizure if:

the patient has had previous myoclonic, absence or partial seizures

the EEG shows unequivocal epileptic discharges

the patient has a congenital neurological deficit

the patient considers the risk of recurrence unacceptable.

3.2 Antiepileptic drug monotherapy

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.^{73, 74, 75, 76, 77, 78, 79, 80, 81} The newer AEDs, lamotrigine and oxcarbazepine seem to be better tolerated and may produce fewer long term side effects and adverse interactions.^{76, 77, 78, 80, 82} Sodium valproate and lamotrigine also have efficacy for absence and myoclonic seizures but lamotrigine can worsen myoclonus in some cases.^{83, 84} Ethosuximide has been used for absence seizures in children for many decades.⁸³ Lamotrigine may have advantages for adolescents, young women and the elderly because it is well tolerated,^{76, 80, 85} has a favourable cognitive and behavioural profile,⁸⁶ does not induce the metabolism of lipid-soluble drugs (such as the hormonal components of the oral contraceptive agent)^{82, 87, 88} and does not lead to weight gain.⁸⁹ Evidence level 1++,1+,1-

Formulations of AEDs are not interchangeable and generic substitution should not be employed.^{90, 91}

Carbamazepine, sodium valproate, lamotrigine and oxcarbazepine can all be regarded as first-line treatments for partial and secondary generalised seizures.

Sodium valproate and lamotrigine are drugs of choice for primary generalised seizures and should also be prescribed if there is any doubt about the seizure types and/or syndrome classification.

All antiepileptic drugs licensed for monotherapy have similar efficacy in newly-diagnosed epilepsy.^{82, 92, 93} Evidence level 1++,1+

The side effect and interaction profiles should direct the choice of drug for the individual patient.

3.3 Management of drug-resistant epilepsy

Drug-resistant epilepsy is defined as continuation of seizures despite optimal monotherapy with two successive first-line AEDs or with one monotherapy and one combination regimen.

The majority of patients with newly-diagnosed epilepsy respond well to AEDs. Failure to do so may be due to:

• an incorrect diagnosis of epilepsy^{2, 93}
• an inappropriate choice of AED for the epilepsy syndrome^{93, 94}
• failure to take the prescribed AED
• an underlying cerebral neoplasm
• covert drug or alcohol abuse.
  Evidence level 1++,1+,1-,2++,2-

Given a correct diagnosis of epilepsy, failure to control seizures completely with the first well-tolerated AED is a powerful predictor of drug-resistant epilepsy.^{72, 95} When two AEDs have failed as monotherapy the chance of seizure-freedom with further monotherapy is very low.⁷² Improvement in seizure control may be obtained by combining AEDs.^{96, 97} 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 eg lamotrigine with sodium valproate^{98, 99} but not with carbamazepine or phenytoin.⁹⁸ Evidence level 1++,1+,1-,2++,2-

3.3.1 DRUG-RESISTANT FOCAL EPILEPSY

Seven AEDs have been licensed in the UK in the last decade. These are, in chronological order, vigabatrin, lamotrigine, gabapentin, topiramate, tiagabine, oxcarbazepine and levetiracetam. Systematic reviews have confirmed the efficacy and tolerability of all these new agents as adjunctive therapy for patients with drug-resistant, focal epilepsy.^{100, 101, 102, 103, 104, 105, 106, 107, 108} The development of concentric visual field defects with vigabatrin has substantially limited its clinical use.¹⁰⁹ Evidence level 1++,1+,1-,2++

3.3.2 DRUG-RESISTANT IDIOPATHIC GENERALISED EPILEPSY

Lamotrigine,^{110, 111, 112} topiramate,^{113, 114} levetiracetam¹¹⁵ and sodium valproate⁸³ have a wide spectrum of activity that includes most types of generalised seizures. Clonazepam may be used for refractory myoclonic seizures. The older agents clobazam¹¹⁶ and acetazolamide¹¹⁷ can be effective for both idiopathic generalised and focal epilepsy when other AEDs have failed. Evidence level 1++,1+,1-,2++

Once the decision has been made to use combination therapy, the patient should be established on the best monotherapy option at the optimal dose, ie one that does not produce side effects.⁸⁴ A range of different AEDs appropriate to the epilepsy syndrome should be added as necessary in sequence, increasing the dose of each slowly to obtain the maximal response with minimal toxicity. The aim should be seizure-freedom. If an encouraging but sub-optimal effect is obtained with a particular combination, it may be worthwhile trying the addition of a small dose of a third AED. Evidence level 1++,1+,1-,2++

The law of diminishing returns may require patient and doctor to accept the persistence of some seizures once a range of treatment options has been tried. Adequacy of seizure control must be balanced with optimal quality of life. Little can be lost by carefully reducing the drug burden in a patient with continuing seizure activity aiming for the most effective combination of two or at most three AEDs. Producing less intrusive episodes, abolishing tonic-clonic seizures, preventing falls and decreasing automatisms can be acceptable end points for some patients.

Failure to respond to appropriate AEDs should prompt a review of the diagnosis of epilepsy and adherence to medication.

Combination therapy should be considered when treatment with two first line AEDs has failed or when the first well-tolerated drug substantially improves seizure control but fails to produce seizure-freedom at maximal dosage.

The choice of drugs in combination should be matched to the patient’s seizure type(s) and should be limited to two or at most three AEDs.

Vigabatrin can be regarded as the drug of last choice because of its association with irreversible visual field defects.

3.4 Antiepileptic drug blood levels

There is no indication for routine monitoring of AED concentrations.^{118, 119, 120} Evidence supports clinically useful dose-response and dose-toxicity relationships for carbamazepine and phenytoin. These relationships do not occur with sodium valproate or any of the newer AEDs. Phenytoin also undergoes saturation kinetics which can make accurate dosage adjustment without concentration monitoring problematical. Even with these two drugs, however, the upper and lower borders of the “target ranges” are imprecise and are not applicable to all patients.¹¹⁸ Evidence level 1+,4

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.

Routine monitoring of AED concentrations is not indicated. Measurement can sometimes be useful in the following circumstances: adjustment of phenytoin dose assessment of adherence and toxicity.

Assay of lamotrigine, vigabatrin, gabapentin, topiramate, tiagabine, oxcarbazepine and levetiracetam concentrations should not be undertaken routinely.

AED blood level measurement is best supervised by an epilepsy specialist.

3.5 Management of provoked seizures

Seizures can be provoked by acute metabolic disturbances, treatment with certain drugs (see Section 3.13) and drug withdrawal (eg alcohol, benzodiazepines, barbiturates). Provoked seizures may occur in the context of drug abuse (heroin, cocaine, methadone, amphetamine, ecstasy). The risk of recurrence of such provoked seizures can be reduced by correction or withdrawal of the provocative factor. The risk of seizures related to acute alcohol withdrawal can be reduced by short term treatment with lorazepam.¹²¹ Commencement of longer term AED treatment is only indicated if unprovoked seizures occur. Evidence level 1+

Provoked seizures can also occur with acute conditions such as encephalitis, head injury, cerebral infarction and cerebral haemorrhage, when they are defined as seizures occurring within seven days of an acute brain insult. There is evidence that treatment can reduce the risk of such provoked seizures in the context of traumatic brain injury (by phenytoin and carbamazepine), craniotomy (by phenytoin) and cerebral malaria (by phenobarbital).^{121, 122} There is no evidence however, that prophylactic treatment and prevention of provoked seizures influences the subsequent development of epilepsy with unprovoked seizures. For acute traumatic brain injury, there is no evidence that the prevention of early provoked seizures by AED treatment influences other outcomes such as death and neurological disability.¹²² There is no justification for the routine prophylactic use of AED treatment to prevent provoked seizures in the context of acute brain insults. If AED treatment is commenced following the occurrence of provoked seizures, it should be used only in the short term, unless unprovoked seizures occur later. Evidence level 1+

Attacks occurring immediately after a concussive closed-head injury have been described as concussive convulsions. There is no evidence that these will recur and AED treatment is not indicated.¹²³ Evidence level 3

When seizures are provoked by metabolic disturbances or drugs, attention should be directed to correction or withdrawal of the provocative factor.

Short term benzodiazepine treatment may be given to reduce the risk of seizures in the context of acute alcohol withdrawal and delirium tremens.

Following an acute brain insult or neurosurgery, prophylactic AED treatment is not indicated.

Following an acute brain insult, AEDs used to treat the provoked seizures should be withdrawn (unless unprovoked seizures occur later).

AED treatment is not indicated for concussive convulsions.

3.6 Antiepileptic drug side effects

Antiepileptic drug side effects are common and a major cause of drug withdrawal. Most are mild but a minority can be life threatening.^{73, 102, 124} 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.¹²⁵ The elderly are more sensitive to AED side effects due to altered pharmacokinetics. Evidence level 1++,1+,3

3.6.1 DOSE-RELATED ADVERSE REACTIONS

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.¹²⁶

3.6.2 IDIOSYNCRATIC ADVERSE DRUG REACTIONS

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.^{127, 128, 129} This incidence is increased if the initial dose is increased rapidly.¹³⁰ Evidence level 2+,4

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.¹²⁷ It is important to note that cross sensitivity occurs between these AEDs in up to 70% of patients. Evidence level 2+

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.^{131, 132} Evidence level 2+,4

Hyponatraemia (sodium <135 but usually >125mmol/L) is seen in about 20% of patients taking carbamazepine or oxcarbazepine; it is usually well tolerated and of no significance.¹³³ Elevation of liver enzymes (d-glutamyl transferase 90%, alkaline phosphatase 30%) is seen in people taking enzyme-inducing AEDs and is usually of no clinical significance.¹³⁴ Clinical symptoms have been shown to be more useful than routine monitoring of liver function in identifying the onset of serious ADRs.^{132, 135} Evidence level 4

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.¹³⁶ Evidence level 4

3.6.3 CHRONIC SIDE EFFECTS

Weight gain is seen with many AEDs⁷⁵ but significant (>10% body weight) weight gain is associated particularly with valproate.⁸⁹ Topiramate can cause weight loss.¹³⁷ Evidence level 1+

Sedation and dizziness are common complaints of patients starting AED therapy but usually resolve with time.¹⁰² Sedation may be less with the newer AEDs.⁸⁶ 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.^{138, 139} Polytherapy is probably associated with more cognitive side effects than monotherapy.¹⁴⁰ Evidence level 1++,2+,4

Osteopenia, osteomalacia and increased risk of hip fracture have been associated with AED use but their aetiology is likely to be multifactorial.^{141, 142, 143, 144} Evidence level 2+

Antiepileptic drugs should be commenced in a dose no higher than recommended by the manufacturer.

Patients should be warned of potential side effects and given clear instructions to seek medical attention urgently for symptoms including rash, bruising or somnolence with vomiting especially in the first weeks of treatment.

Patients taking AEDs should receive dietary and other lifestyle advice to minimise the risk of osteoporosis.

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

3.7 Antiepileptic drug withdrawal

Estimates of the risks of seizure recurrence after discontinuation of AEDs were provided by a large, multicentre, randomised, prospective trial of continued antiepileptic treatment versus slow withdrawal in adults and children with epilepsy, who had been seizure free for at least two years.¹⁴⁵ 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.¹⁴⁶ This has been used to calculate the risks of seizure recurrence with continued treatment or with slow AED withdrawal (see Tables 2 and 3). 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. Evidence level 1++

No information is available on the risks of seizure recurrence following drug withdrawal in adults who have been less than two years seizure free, although for children the risks are higher after less than two years seizure freedom than for more than two years.¹⁴⁷

The effect of different rates of AED withdrawal on the risk of seizure recurrence has not been adequately studied.

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.

Prognostic index indicators can be used to give an estimate of the risks of seizure recurrence following AED withdrawal (see Tables 2 and 3).

The question of continued treatment or AED withdrawal should be discussed with people with epilepsy, who are at least two years seizure free, so that they can make an informed choice. Factors to be discussed should include driving, employment, fear and risks of further seizures and concerns about prolonged AED treatment.

The rate of withdrawal of AEDs should be slow, usually over a few months, and longer with barbiturates and benzodiazepines. One drug should be withdrawn at a time.

Table 2: Prognostic index for recurrence of seizures after remission of epilepsy for patients taking only one antiepileptic drug (AED)

Risk of seizure recurrence by two years (%)

*TC: history of idiopathic or secondary generalised tonic-clonic seizures
My: history of myoclonic seizures with tonic-clonic seizures (myoclonic seizures rarely occur alone)
Oth: history of seizures other than tonic-clonic or myoclonic

Risk of seizure recurrence by two years (%)

*TC: history of idiopathic or secondary generalised tonic-clonic seizures
My: history of myoclonic seizures with tonic-clonic seizures (myoclonic seizures rarely occur alone)
Oth: history of seizures other than tonic-clonic or myoclonic

3.8 Psychological treatment of epilepsy

A variety of treatment types has been used in the psychological management of epilepsy.¹⁴⁸ There is evidence that seizures may respond to operant and/or classical conditioning and that seizure spread may be inhibited by the patient’s own intervention, either by interruption strategies or EEG biofeedback. Evidence level 1+,2++,2+,3

Anxiety or stress may precipitate seizures, possibly through hyperventilation.¹⁴⁹ Treatments aimed at reducing anxiety may reduce seizure frequency^{150, 151, 152, 153, 154} and are free of significant side effects. Psychological symptoms associated with epilepsy may merit treatment in their own right.¹⁵⁵ Evidence level 1+,2++,2+,3

Psychological treatments are not an alternative to pharmacological treatments, but their use can be considered in patients with poorly controlled seizures.

3.9 Complementary therapy for epilepsy

Complementary therapy is increasingly popular with patients, who may use this in addition to conventional medication.^{156, 157} The term covers a wide variety of treatments such as acupuncture, chiropractic, herbal medicine, homeopathy, osteopathy and yoga. There is no evidence that these improve seizure control.^{158, 159} Evidence level 4

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.¹⁶⁰ 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. Evidence level 4

Some aromatherapy preparations (eg hyssop, rosemary, sweet fennel, sage and wormwood) may have an alerting effect on the brain and so may exacerbate seizures.^{161, 162} Evidence level 4

3.10 Surgical referral

Neurosurgical procedures are an effective treatment for some patients with epilepsy resistant to drug treatment.^{163, 164} Patients can be classified as probably having drug resistant epilepsy once they have failed to obtain seizure control with two appropriate AEDs given in adequate dosage (see Section 3.3).⁷² It is important that surgery be considered as soon as it is established that the epilepsy is drug resistant, as the benefits will be greater in younger patients. Some neurosurgical procedures involve resection of part of the brain, and the aim is to obtain complete seizure freedom. For the most commonly performed procedures, involving anterior and medial temporal lobe resection, about 70% of patients will become seizure free.¹⁶⁵ Other procedures are palliative and include corpus callosotomy, subpial transection and vagus nerve stimulation.¹⁶⁶ Assessment for suitability for surgery should be performed in a specialist unit. For each individual the potential benefits of improved seizure control, quality of life and possible reduction in antiepileptic medication need to balanced against the risks of the surgical procedure. Evidence level 1+

Referral for assessment for neurosurgical treatment should be considered if the epilepsy is drug resistant.

Assessment as to suitability for a potentially curative resective procedure should be made before consideration of palliative procedures such as vagus nerve stimulation.

3.11 Management of status epilepticus

Status epilepticus has been defined as a condition in which “epileptic activity persists for 30 minutes or more, causing a wide spectrum of clinical symptoms, ...”.¹⁶⁷

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.^{168, 169, 170} 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.^{168, 171} EEG recording may be necessary to confirm the diagnosis and to assess control, when seizures are clinically subtle (eg in partial status, or following treatment of tonic-clonic status epilepticus).¹⁷² Evidence level 3

3.11.1 GENERALISED TONIC-CLONIC STATUS EPILEPTICUS

Recommendations for treatment are based on two large prospective, randomised trials of the management of status epilepticus^{173, 174} and on small or uncontrolled studies, physiological principles and pharmacokinetic considerations.^{167, 175, 176, 177, 178, 179, 180} 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.¹⁷³ 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.¹⁷⁴ Lorazepam has the advantage over diazepam of a much longer 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). Evidence level 1++,3,4

IMMEDIATE MEASURES

In the community or in hospital, patients with generalised tonic-clonic status epilepticus should be managed immediately as follows (with local protocols being in place): secure airway give oxygen assess cardiac and respiratory function secure IV access in large veins.

Give lorazepam 4mg IV or diazepam 10 mg IV if lorazepam is unavailable. This can be repeated in hospital after 10 minutes if there is no response. If there is a delay in gaining IV access in the community: give diazepam 10 20mg rectally (rectal solution or IVsolution).

In hospital: collect blood for full blood count, urea and electrolyte, liver function tests, calcium, glucose, clotting, AED levels and storage for later analyses measure blood gases to assess extent of acidosis establish aetiology. Give 50ml 50% glucose IV if there is any suggestion of hypoglycaemia and IV thiamine (given as Pabrinex two pairs of ampoules) if there is any suggestion of alcohol abuse or impaired nutritional status.

WITHIN 30 MINUTES

For sustained control in patients with established epilepsy, within 30 minutes: give usual AED treatment orally or by nasogastric tube (or IV if necessary for phenytoin, sodium valproate and phenobarbital).

For sustained control in other patients or if seizures continue, within 30 minutes: give fosphenytoin in a dose of 18mg/kg phenytoin equivalent (PE) IV, up to 150mg/min with ECG monitoring; or phenytoin 18mg/kg IV, 50mg/min with ECG monitoring or phenobarbital 15mg/kg IV, 100mg/min. Rates of infusion may need to be reduced if hypotension or arrythmia occur or in elderley or renal/ hepatic impairment.

Clear policies should be in place to avoid confusion between doses, formulations, routes and rates of administration of fosphenytoin and phenytoin.

LONGER THAN 30 MINUTES

If status epilepticus persists the patient needs to be admitted to an intensive treatment unit (ITU) and anaesthetised with EEG monitoring. Midazolam, pentobarbital (unlicensed), propofol or thiopentone are most commonly used in these circumstances.¹⁸⁰ Evidence level 4

If status persists, then within 60 minutes: admit to ITU and administer general anaesthesia monitor using EEG to assess seizure control refer for specialist advice.

3.11.2 NON-CONVULSIVE STATUS EPILEPTICUS

Patients with non-convulsive status epilepticus should be managed as follows: maintain or reinstate usual oral AED treatment consider lorazepam 4mg IV or diazepam 10 mg IV refer for specialist advice.

3.11.3 PATIENTS WITH RECURRENT PROLONGED OR SERIAL SEIZURES IN THE COMMUNITY

Carers of patients with recurrent episodes of serial seizures, or prolonged seizures may be able to terminate the episodes and perhaps prevent the development of status epilepticus by the administration of rectal diazepam 10-20mg.^{181, 182} An administration protocol should be followed (see Section 3.13).^{183, 184} Buccal or intranasal midazolam has also been used as a more convenient (but unlicensed) alternative, mainly in children, and needs further assessment.^{185, 186} Evidence level 1+,1-,3

Patients with recurrent prolonged or serial seizures in the community should be initially managed by carers who should give diazepam 10-20mg rectally according to an agreed protocol (protocols must include advice on when to transfer to hospital).

3.12 Management of people with learning disability and epilepsy

People with learning disability and epilepsy should have access to the same range of investigations and treatment as the rest of the population.^{187, 188} The high prevalence of epilepsy associated with learning disability is at its greatest (about 50%) in people with severe disability and cerebral palsy.¹⁸⁹ Quality of life may be affected because of injuries sustained during seizures and because of the side effects of medication.¹⁹⁰ An excess mortality has also been reported.¹⁹¹ In some adults who have learning disability it may be difficult to distinguish epilepsy from psychiatric illness, emotional and behavioural outbursts.^{188, 192} 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.¹⁹³ 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. Evidence level 4

In the management of people with learning disability and epilepsy: adequate time should be allowed for the consultation the carer should know the patient and bring relevant information on seizure type, frequency, possible side effects of medication, general health and behaviour to the consultation information in an accessible form should be available to clients and carers there should be a multidisciplinary approach to treatment, delivered by professionals with an expertise in epilepsy, to improve quality of life. Community learning disability nurses have an important role in liaising between the specialist services and clients and carers.

3.13 Advice on rectal diazepam or equivalent emergency medication

Rectal diazepam is a relatively safe and effective medication for the control of serial and/or prolonged seizures in patients in the community. Parents and carers who have been trained in the procedure can administer the medication as a first aid measure by following clear written guidelines set by the prescribing doctor. Evidence level 4

Recognised training should be given to carers and updated at regular intervals; a care plan should be used to ensure consistency of treatment.^{183, 184, 194} Evidence level 4

All carers of patients with learning disability and epilepsy who may require rectal diazepam, should receive recognised training in its administration. Retraining should take place every two years.

A care plan should be drawn up in consultation with the GP and/or specialist service, used by everyone working with the individual client, and reviewed at regular intervals.

Adequate support and instruction should be given to families.

3.14 Drugs which exacerbate epileptic seizures

Drugs may occasionally precipitate seizures particularly in patients with epilepsy or other risk factors.¹⁹⁵ Commonly used drugs are listed in Table 4 (causality is not always certain and may be multifactorial).^{196, 197, 198, 199, 200, 201, 202, 203, 204, 205} Evidence level 4

Table 4: Drugs which may precipitate epileptic seizures

Mechanisms for triggering seizures may include:

• lowering of seizure threshold - this is usually dose/plasma concentration dependent and factors such as renal impairment (eg pethidine) or coadministration of interacting drugs (eg ciprofloxacin/theophylline) may contribute
• decrease in AED levels via pharmacokinetic drug interactions (eg hepatic microsomal enzyme induction with rifampicin)
• effects secondary to other medical causes precipitated by drugs eg drug-induced hyponatraemia or serotonin syndrome
• individual AEDs which themselves may cause worsening of some types of seizures⁹⁴
• drug withdrawal eg from AEDs, alcohol, benzodiazepines, barbiturates and baclofen.^{206, 207}
  Evidence level 3,4

All healthcare professionals should be vigilant for prescription of drugs that may cause or exacerbate seizures in patients with epilepsy.

A wide variety of drugs has 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, eg 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.208

3.15 Management of patients with epilepsy in the perioperative period

Loss of seizure control due to missed oral medication can occur in the context of surgery, labour, and when there is difficulty in swallowing. Table 5 lists some alternative routes of AED administration. Sometimes changes in drug doses or frequency will be necessary due to pharmacokinetic differences between formulations.

Table 5: Alternative methods of AED administration

*safety advantage over intravenous route

Healthcare professionals should consider the possible consequences of missed AED doses when planning hospital admission.

AEDs should be administered by alternative routes or by giving additional doses as appropriate. When patients have been designated nil by mouth prior to surgery, they should still be given their usual oral AED unless absorption is impaired.

When a prolonged problem with administration of drugs not available parenterally is anticipated, and oral or enteral administration is not possible, consideration should be given to seizure prophylaxis with parenterally available agents.