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BMJ Clin Evid. 2015; 2015: 1201.
Published online 2015 April 17.
PMCID: PMC4400652

Epilepsy (generalised seizures)

J. Helen Cross, MB,ChB, PhD, FRCP, FRCPCH, Deputy Head of the Developmental-Neurosciences Programme, The Prince of Wales's Chair of Childhood Epilepsy

Abstract

Introduction

About 3% of people will be diagnosed with epilepsy during their lifetime, but about 70% of people with epilepsy eventually go into remission.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of additional treatments in people with drug-resistant epilepsy characterised by generalised seizures? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found four studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety on the addition of the following interventions: lacosamide, lamotrigine, levetiracetam, perampanel, and zonisamide versus the addition of placebo.

Key Points

Epilepsy is a group of disorders rather than a single disease.

Seizures can be classified as generalised or focal. This review examines the effects of additional treatments in people with drug-resistant epilepsy characterised by generalised seizures.

During their lifetime, about 3% of people will be diagnosed with epilepsy, but about 70% of people with epilepsy eventually go into remission.

Adding lamotrigine seems to be more effective than adding placebo at reducing seizure frequency in people with drug-resistant epilepsy characterised by generalised seizures.

Adding levetiracetam seems to be more effective than adding placebo at reducing seizure frequency in people with drug-resistant epilepsy characterised by generalised seizures.

The RCTs we found were relatively short term (12–24 weeks) and we found no longer term studies. There is a need for further long-term studies to confirm the ongoing efficacy and safety of agents.

We don’t know about the benefits of adding lacosamide, perampanel, or zonisamide compared to adding placebo, as we found no systematic reviews or RCTs.

Clinical context

About this condition

Definition

Epilepsy is a group of disorders rather than a single disease. Seizures can be classified by type as generalised (generalised tonic clonic, absence, myoclonic, tonic, and atonic seizures) or focal (previously categorised as simple partial, complex partial, and secondary generalised tonic clonic seizures). A person is considered to have epilepsy if he/she has had two or more unprovoked seizures or has had a single seizure and is regarded as at significant risk of a second. When a diagnosis of epilepsy has been made, the epilepsy syndrome should be characterised if possible, dependent on the electroclinical features (e.g., childhood absence epilepsy is characterised by age of onset [5-10 years], frequent short absence seizures, and an EEG demonstrating 3 Hz spike and wave). The optimal first-line medication will be chosen, dependent on the syndrome; the intervention most likely to lead to benefit and least likely to cause aggravation of seizures. Valproate remains the most effective medication as first-line treatment in many of the epilepsies characterised by predominantly generalised seizures (e.g., genetic generalised epilepsy), especially those including generalised tonic clonic seizures. Ethosuximide may be the first drug of choice in generalised epilepsies characterised by absence seizures. Side effects of medication also need to be kept to a minimum. There has been emerging concern about the effect of valproate on the unborn child, specifically with regard to postnatal neurocognitive development. Consequently it is now not considered as treatment of choice in women of child bearing age. This has led to wider use of levetiracetam and lamotrigine as alternative first line treatment in this population. This review deals with additional pharmacological treatments for people with drug-resistant epilepsy characterised by generalised seizures. Status epilepticus is not covered in this review.

Incidence/ Prevalence

Epilepsy is common, with an estimated average prevalence of 5.5/1000 people in Europe, 6.8/1000 people in the US, and 7.5/1000 people in Australia. Prevalence rates in developing countries vary widely, with studies carried out in sub-Saharan Africa reporting rates of 5.2 to 74.4/1000 people, studies in Asia reporting overall prevalence rates of 1.5 to 14.0/1000 people, and Latin America reporting rates of 17 to 22/1000 people. The worldwide incidence of epilepsy (defined as 2 or more unprovoked seizures occurring at least 24 hours apart) is 50.4/100,000 people per year. The incidence is approximately 45.0/100,000 per year for high-income countries and 81.7/100,000 per year for low- and middle-income countries.The worldwide incidence of single unprovoked seizures is 23 to 61/100,000 person-years. About 3% of people will be diagnosed with epilepsy at some time in their lives.

Aetiology/ Risk factors

Epilepsy is a symptom rather than a disease, and it may be caused by various disorders involving the brain. Where possible, an epilepsy will be described as an electroclinical syndrome. The causes/risk factors, however, remain wide and include birth/neonatal injuries, congenital or metabolic disorders, head injuries, tumours, infections of the brain or meninges, genetic defects, malformations of the brain, degenerative disease of the brain, cerebrovascular disease, or demyelinating disease; these may be grouped as genetic, structural/metabolic, or unknown.

Prognosis

After their first seizure, about 60% of untreated people have no further seizures in the following 2 years. Prognosis is good for most people with epilepsy. About 70% go into remission, defined as being seizure-free for 5 years on or off treatment. This leaves 20% to 30% who continue to have epileptic seizures, despite treatment with anti-epileptic drugs. This group are often treated with multiple anti-epileptic drugs.

Aims of intervention

To reduce the risk of subsequent seizures and to improve the prognosis of the seizure disorder; to improve quality of life; to minimise adverse effects of treatment.

Outcomes

Seizure frequency percentage reduction in seizure frequency, proportion of responders (response defined as at least 50% reduction in seizure frequency); quality of life; adverse effects.

Methods

BMJ Clinical Evidence search and appraisal April 2014. The following databases were used to identify studies for this systematic review: Medline 1966 to April 2014, Embase 1980 to April 2014, and The Cochrane Database of Systematic Reviews 2014, issue 4 (1966 to date of issue). Additional searches were carried out in the the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were then assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were published RCTs and systematic reviews of RCTs in the English language, at least double-blinded and containing at least 20 individuals (at least 10 per arm), of whom at least 80% were followed up. There was a minimum length of follow-up of 3 months. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We aimed to include studies in people with generalised seizures (excluding status epilepticus) or where a subgroup analysis was carried out in people with generalised epilepsy. However, where studies included a mixture of partial and generalised epilepsy, we included studies in which at least 60% of people had generalised epileptic seizures. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the BMJ Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table 1
GRADE evaluation of interventions for Epilepsy (generalised seizures)

Glossary

Absence seizure
Previously known as 'petit mal'. Brief episodes of unconsciousness with vacant staring, sometimes with fluttering of the eyelids, as if "daydreaming". People with absence seizure do not fall to the ground and generally have a rapid recovery. The condition is rare in adults.
Atonic seizure
Momentary loss of limb muscle tone causing sudden falling to the ground or drooping of the head.
Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Tonic clonic seizure
Also known as a convulsion or 'grand mal' attack. The person will become stiff (tonic) and collapse, and have generalised jerking (clonic) movements. Breathing might stop and the bladder might empty. Generalised jerking movements lasting typically for a few minutes are followed by relaxation and deep unconsciousness, before the person slowly comes round. People are often tired and confused, and may remember nothing. Tonic clonic seizures may follow simple partial or complex partial seizures (see above), where they are classified as secondary generalised tonic clonic seizures. Tonic clonic seizures occurring without warning and in the context of generalised epilepsy are classified as generalised tonic clonic seizures.

Notes

Disclaimer

The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

Notes

Treatment of typical absence seizures in children, see review on Absence seizures in children.

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2015; 2015: 1201.
Published online 2015 April 17.

Addition of lacosamide compared with adding placebo in people with drug-resistant epilepsy characterised by generalised seizures

Summary

We found no direct information from RCTs about whether the addition of lacosamide is better than placebo in people with drug-resistant epilepsy characterised by generalised seizures.

Benefits

Adding lacosamide versus adding placebo:

We found no systematic review or RCTs.

Harms

Antiepileptic drugs have been associated with an increased risk of suicidal behaviour and ideation.

See Comment section for further information on potential harms of anti-epileptics.

Adding lacosamide versus adding placebo:

We found no RCTs.

Comment

Lacosamide is increasingly used as add-on therapy where other medication has failed. There is little evidence to suggest the medication is problematic; in particular, there is little evidence of aggravation of seizures.

Some anti-epileptic drugs (AEDs) are associate with an increased risk for congenital malformations in the unborn child in women taking AEDs while pregnant. There has been increasing concern about the effects of valproate on longer term cognition and behaviour in children born to mothers taking valproate during pregnancy. There is no data available on teratogenic effects for lacosamide.

Clinical guide

Lacosamide is available to be used as an add-on agent where existing anti-epileptic drugs have failed. Individuals initiated on this medication should be under on-going review by an epilepsy specialist.

Substantive changes

Addition of lacosamide compared with adding placebo in people with drug-resistant epilepsy characterised by generalised seizures New option. Categorised as 'unknown effectiveness'.

2015; 2015: 1201.
Published online 2015 April 17.

Addition of lamotrigine compared with adding placebo in people with drug-resistant epilepsy characterised by generalised seizures

Summary

SEIZURE FREQUENCY Adding lamotrigine compared with adding placebo: Adding lamotrigine seems more effective than adding placebo at decreasing the frequency of generalised tonic clonic seizures and at increasing the proportion of people with a 50% or greater reduction in generalised seizures ( moderate-quality evidence ).

Benefits

Adding lamotrigine versus adding placebo:

We found one systematic review and one subsequent RCT comparing addition of lamotrigine with addition of placebo in people who had not responded to usual drug treatment.

The systematic review (search date 2010, 2 RCTs, 143 people, aged 2–55 years, 51% men) compared the addition of lamotrigine with placebo in people with generalised tonic clonic seizures with or without other generalised seizure types (e.g., absence or myoclonic seizures). The review did not pool the data due to differences in study design between the two RCTs (one was a crossover RCT and the other a parallel RCT). The first RCT (crossover design, 26 people with absence, myoclonic, or generalised tonic clonic seizures or a combination of these [excluding Lennox-Gastaut epilepsy], aged 15–50 years [mean age 29 years], 42% male) compared adding lamotrigine (75 mg or 150 mg once-daily) with adding placebo to usual drug treatment (up to 4 drugs allowed, including valproate [26 people], carbamazepine [11 people], clonazepam [5 people], phenytoin [3 people], ethosuximide [2 people], primidone [2 people]). The RCT reported results after crossover and separately by seizure type. It found that, in people with generalised tonic clonic or absence seizures, adding lamotrigine significantly increased the proportion of people with a 50% or greater reduction in seizure rate (percentage reduction in seizure rate calculated from the individual seizure rate in the adjunctive-lamotrigine treatment phase compared with the seizure rate in the adjunctive placebo phase) after 12 weeks’ treatment (proportion of people with at least a 50% reduction in seizure rate: generalised seizures: 7/14 [50%], P = 0.03; absence seizures: 5/15 [33%], P <0.001). It found that, in people with myoclonic seizures, lamotrigine did not reduce seizure rate by at least 50% compared with placebo; however, statistical analysis was not possible for this group owing to the small number of people (proportion of people with at least a 50% reduction in seizure rate: myoclonic seizures: 0/2 [0%], statistical assessment not reported).

The second RCT (parallel design, 121 people with primary generalised tonic clonic seizures, aged 2–55 years [mean age about 26 years], 53% men) compared adding lamotrigine (maximum 200–400 mg/day) with adding placebo to usual drug treatment (up to 2 drugs allowed). The RCT included a dose-escalation phase (lamotrigine dose titrated to target dose over 7 weeks for people aged 12 years or more, or over 12 weeks for children aged 2–12 years, versus placebo), followed by a maintenance phase (target lamotrigine dose versus placebo for 12 weeks). It found that adding lamotrigine significantly increased the proportion of people with a 50% or greater reduction in primary generalised tonic clonic seizures over both phases (19 or 24 weeks) and over the maintenance phase only (12 weeks) (proportion of people with a 50% or greater reduction in primary generalised tonic clonic seizures over both dose-escalation and maintenance phases: 64% with lamotrigine v 39% with placebo; P <0.05; over maintenance phase only: 72% with lamotrigine v 49% with placebo; P <0.05; absolute numbers not reported; intention-to-treat analysis). A high proportion of people (34/121 [28%]) in the RCT did not complete the study; however, the RCT included data on all randomised people who received at least one dose of study medication (117 people) in its intention-to-treat analysis.

The subsequent RCT (153 people with primary generalised tonic clonic seizures with or without other generalised seizure types, 3 or more seizures during 8-week baseline period, aged at least 13 years, 51% male) compared adding extended-release lamotrigine (200−500 mg/day) with adding placebo to usual drug treatment (up to 2 drugs allowed). It found that adding extended-release lamotrigine significantly decreased frequency of primary generalised tonic clonic seizures compared with placebo (median percentage reduction in weekly seizure frequency from baseline: 75% with lamotrigine v 32% with placebo; P <0.0001). The addition of extended-release lamotrigine also significantly increased the proportion of people experiencing a 50% or greater reduction in seizure frequency (70% with lamotrigine v 32% with placebo; P <0.0001; absolute results presented graphically).

Harms

Anti-epileptic drugs have been associated with an increased risk of suicidal behaviour and ideation.

See the Comment section for further information on potential harms of anti-epileptic drugs.

Adding lamotrigine versus adding placebo:

The first crossover RCT identified by the review found higher rates of rash with adding lamotrigine compared with adding placebo to usual care (7/26 [27%] with lamotrigine v 0/26 [0%] with placebo; significance assessment not reported). Two of these people withdrew from the study owing to rash with lamotrigine. The second parallel RCT, identified by the review, did not report rash in either treatment group. It found higher rates of dizziness, nausea, and somnolence with adding lamotrigine compared with adding placebo to usual care (dizziness: 5% with lamotrigine v 2% with placebo; nausea: 5% with lamotrigine v 3% with placebo; somnolence: 5% with lamotrigine v 2% with placebo; absolute results and significance assessment not reported).

The subsequent RCT found no significant difference between extended-release lamotrigine and placebo groups in the number of people with an adverse effect. Headache was the most common adverse effect reported in both treatment groups. No serious rashes were reported in either treatment group. Adverse effects led to withdrawal from the study in one person in the lamotrigine extended-release group and two people in the placebo group.

Comment

Few RCTs have compared second-line drugs directly with each other. The RCTs did not report outcomes separately for adults and children. It was noted that rash was more prevalent with lamotrigine, and this risk is higher when the medication is added to sodium valproate; although, the risk can be minimised by a slow cautious introduction.

Some anti-epileptic drugs (AEDs) are associated with an increased risk for congenital malformations in the unborn child in women taking AEDs while pregnant. The risk appears low with lamotrigine monotherapy. There has also been increasing concern about the effects of valproate on longer term cognition and behaviour in children born to mothers taking valproate during pregnancy. However, lamotrigine does not appear to be implicated.

Drug safety alert

Lamotrigine (December 2010)

A drug safety alert has been issued on the risk of aseptic meningitis associated with lamotrigine. (www.fda.gov).

Clinical guide

Lamotrigine has been demonstrated to be an effective medication in add-on therapy to first-line anti-epileptic drugs. It has been demonstrated to be effective in most epilepsies characterised by generalised seizures, although the clinician should note it may aggravate myoclonic seizures. Although there is an early risk of rash on initiation, in the longer term the medication appears to have a beneficial safety profile. The risk is highest when introduced with sodium valproate, although synergistic action may be seen on this combination. Although its safety profile for use in pregnancy appears favourable, adjustment in dose is likely to be required in some women through pregnancy and postpartem.

Substantive changes

Addition of lamotrigine compared with adding placebo in people with drug-resistant epilepsy characterised by generalised seizures Option restructured. Categorised as 'likely to be beneficial'.

2015; 2015: 1201.
Published online 2015 April 17.

Addition of levetiracetam compared with addition of placebo in people with drug-resistant epilepsy characterised by generalised seizures

Summary

SEIZURE FREQUENCY Adding levetiracetam compared with adding placebo: Adding levetiracetam seems to be more effective than adding placebo at increasing the proportion of responders (defined by at least a 50% reduction in seizure frequency) and seems to be more effective at increasing the proportion of people who are seizure-free at 16 and 24 weeks ( moderate-quality evidence ).

Benefits

Adding levetiracetam versus adding placebo:

We found one systematic review (search date 2012, 2 RCTs, 284 people) comparing the addition of levetiracetam with the addition of placebo in people who had not responded to usual drug treatment. It included two RCTs. The systematic review compared the addition of levetiracetam with the addition of placebo in people with primary generalised seizure. The first RCT (164 people, aged 4–65 years [mean age 29 years], 44% male, at least 3 generalised tonic clonic seizures/8-week baseline period) compared adding levetiracetam with adding placebo to usual treatment (1 or 2 antiepileptic drugs, including valproate [86 people], lamotrigine [45 people], carbamazepine [31 people], topiramate [19 people], phenytoin [17 people]). The second RCT (120 people, aged 12–65 years, 36% male, at least 8 days of myoclonic seizures/8-week baseline) compared adjunctive levetiracetam at 3000 mg daily with placebo for 16 weeks. The review found that adding levetiracetam significantly increased the proportion of responders (defined as at least a 50% reduction in seizure frequency per week from baseline) compared with placebo at 16 or 24 weeks (50% reduction in weekly seizure frequency: 93/140 [66%] with levetiracetam v 52/144 [36%] with placebo; OR 3.70, 95% CI 2.24 to 6.12, P <0.00001). The review also found that levetiracetam significantly increased the proportion of people seizure-free compared with placebo at 16 to 24 weeks (37/140 [26%] with levetiracetam v 11/144 [8%] with placebo; OR 4.59, 95% CI 2.20 to 9.56, P <0.00001).

Harms

Antiepileptic drugs have been associated with an increased risk of suicidal behaviour and ideation.

See Comment section for further information on potential harms of anti-epileptics.

Adding levetiracetam versus adding placebo:

The review found no significant difference in rates of adverse drug reactions between levetiracetam and placebo in both RCTs. The first RCT included in the review found similar rates of any adverse effect or drug-related adverse effects between groups (57/79 [72%] with levetiracetam v 57/84 [68%] with placebo; P = 0.55). The most frequently reported adverse effects with levetiracetam in the RCT were nasopharyngitis, headache, fatigue, dizziness, and diarrhoea.

The second RCT included in the review found similar rates of treatment-emergent adverse effects in both groups (45/60 [75%] with levetiracetam v 40/60 [67%] with placebo; P = 0.31). The most frequently reported adverse effects with levetiracetam in the RCT were headache, somnolence, neck pains, and pharyngitis.

The review included 13 RCTs of levetiracetam in various different population groups. It noted that, overall, the adverse effects of somnolence, agitation, dizziness, asthenia, and infection occurred more often in the levetiracetam group. The review reported that serious adverse reactions such as kidney and liver functional abnormality, rash, and decreases in white blood cells occurred rarely in both drug and placebo groups.

Levetiracetam versus other antiepileptic drugs:

We found no RCTs.

Comment

Few RCTs have compared second-line drugs directly versus each other. The RCTs did not report outcomes separately for adults and children.

The review noted that included RCTs reported results over quite a short time period, and that there was a need for further long-term studies to confirm the efficacy and safety of levetiracetam. Clinical practice has revealed change in mood and behaviour in some individuals initiated on levetiracetam, this may be minimised by taking a cautious approach to introduction.

Some anti-epileptic drugs (AEDs) are associated with an increased risk for congenital malformations in the unborn child in women taking AEDs while pregnant. Data from epilepsy registries suggest a low risk for malformations with levetiracetam exposure, particularly in monotherapy with a slightly increased risk from polytherapy. There has been increasing concern about the effects of valproate on longer term cognition and behaviour in children born to mothers taking valproate during pregnancy. Early data suggest this is not the case with levetiracetam.

Clinical guide

Levetiracetam has been shown to be an effective as an add-on to existing treatment in epilepsy characterised by generalised tonic clonic seizures. NICE guidelines outline its consideration as first-line treatment; although, where it has not been used in this context it should be considered as an initial add-on therapy. Lack of interactions with other medications can put levetiracetam ahead of lamotrigine in the treatment of individuals with epilepsy characterised by generalised seizures.

Substantive changes

Addition of levetiracetam compared with addition of placebo in people with drug-resistant epilepsy characterised by generalised seizures Option restructured. One systematic review added. Categorised as 'likely to be beneficial'.

2015; 2015: 1201.
Published online 2015 April 17.

Addition of perampanel compared with the addition of placebo in people with drug-resistant epilepsy characterised by generalised seizures

Summary

We found no direct information from RCTs about whether the addition of perampanel is better than placebo in people with drug-resistant epilepsy characterised by generalised seizures.

Benefits

Adding perampanel versus adding placebo:

We found no systematic review or RCTs.

Harms

Antiepileptic drugs have been associated with an increased risk of suicidal behaviour and ideation.

See the Comment section for further information on potential harms of anti-epileptics.

Adding perampanel versus adding placebo:

We found no RCTs.

Comment

Perampanel is increasingly used as add-on therapy where other medication has failed. Dizziness is a prominent side effect, avoided by giving the medication late at night before bed. There is little evidence of aggravation of seizures.

Some anti-epileptic drugs (AEDs) are associated with an increased risk for congenital malformations in the unborn child in women taking AEDs while pregnant. There has been increasing concern about the effects of valproate on longer term cognition and behaviour in children born to mothers taking valproate during pregnancy. There is no data available on teratogenic effects for perampanel.

Clinical guide

Perampanel is available to be used as an add-on agent where existing anti-epileptic drugs have failed to control seizures. Individuals initiated on this medication should be under on-going review by an epilepsy specialist.

Substantive changes

Addition of perampanel compared with the addition of placebo in people with drug-resistant epilepsy characterised by generalised seizures New option. Categorised as 'unknown effectiveness'.

2015; 2015: 1201.
Published online 2015 April 17.

Addition of zonisamide compared with the addition of placebo in people with drug-resistant epilepsy characterised by generalised seizure

Summary

We found no direct information from RCTs about whether the addition of zonisamide is better than placebo in people with drug-resistant epilepsy characterised by generalised seizures.

Benefits

Adding zonisamide versus adding placebo:

We found no systematic review or RCTs.

Harms

Antiepileptic drugs have been associated with an increased risk of suicidal behaviour and ideation.

See Comment section for further information on potential harms of anti-epileptics.

Adding zonisamide versus adding placebo:

We found no RCTs.

Comment

Zonisamide is increasingly used as add-on therapy where other medication has failed. Somnolence and loss of appetite are noticed in clinical practice. There is little evidence of aggravation of seizures.

Some anti-epileptic drugs (AEDs) are associated with an increased risk for congenital malformations in the unborn child in women taking AEDs while pregnant. There has been increasing concern about the effects of valproate on longer term cognition and behaviour in children born to mothers taking valproate during pregnancy. There is no data available on teratogenic effects for zonisamide.

Clinical guide

Zonisamide is available to be used as an add-on agent where existing anti-epileptic drugs have failed. Individuals initiated on this medication should be under on-going review by an epilepsy specialist.

Substantive changes

Addition of zonisamide compared with the addition of placebo in people with drug-resistant epilepsy characterised by generalised seizure New option. Characterised as 'unknown effectiveness'.


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