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Effectiveness of antiseizure therapies in the treatment of tonic or atonic seizures/drop attacks
Review question
What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Introduction
A drop attack may be defined as any event that may cause an individual to suddenly drop to the floor. In the context of epilepsy, these may be the result of atonic (generalised loss of tone) or tonic (sustained generalised body stiffening) seizures. These are characteristic seizures of Lennox-Gastaut syndrome, but are also seen in the context of other epilepsy syndromes and aetiologies. These seizure types are particularly relevant to quality of life as they may cause injury, through unpredictable sudden collapse to the floor (atonic seizures), or in the context of tonic seizures being thrown forward or backwards. The aim of this review is to determine which antiseizure therapies are effective in the treatment of tonic or atonic seizures/drop attacks.
Summary of the protocol
Please see Table 1 for a summary of the Population, Intervention, Comparison and Outcome (PICO) characteristics of this review.
In order to ensure consistency with evidence report L on Lennox Gastaut syndrome, the committee agreed that it was appropriate to amend this protocol to include a number of anti-seizure medications (ASMs) which they believed to be of relevance in the treatment of people with tonic or atonic seizures/drop attacks. These were:
- carbamazepine
- clobazam
- clonazepam
- gabapentin
- lacosamide
- oxcarbazepine
- pregabalin
- tiagabine
- vigabatrin
For further details see the review protocol in appendix A.
Methods and process
This evidence review was developed using the methods and process described in Developing NICE guidelines: the manual. Methods specific to this review question are described in the review protocol in appendix A and the methods document (supplementary document 1).
Declarations of interest were recorded according to NICE’s conflicts of interest policy.
Clinical evidence
Included studies
Eight randomised controlled trials (RCTs) and one follow-up study were identified for inclusion in this review (Arzimanoglou 2019, Conry 2009, Dodson 1993, Felbamate study group 1993, Glauser 2008, Motte 1997, Ng 2011, Ohtsuka 2014, Sachdeo 1999).
Two of the included articles provided data from the same population, comparing felbamate with placebo: 1 RCT (Felbamate study group 1993) and 1 follow-up study (Dodson 1993).
One RCT compared add-on rufinamide with any other add-on antiseizure medication (Arzimanoglou 2019); 1 RCT compared add-on low-dose clobazam with add-on high-dose clobazam (Conry 2009); 1 RCT and 1 follow-up study reported results from a study comparing add-on felbamate with placebo (Felbamate study group 1993, Dodson 1993); 2 RCTs compared add-on rufinamide with placebo (Glauser 2008, Ohtsuka 2014); 1 RCT compared add-on lamotrigine with placebo (Motte 1997); 1 RCT compared add-on dose-ranging clobazam with placebo (Ng 2011); and 1 RCT compared add-on topiramate with placebo (Sachdeo 1999).
The included studies are summarised in Table 2 to Table 8.
See the literature search strategy in appendix B and study selection flow chart in appendix C.
Excluded studies
Studies not included in this review with reasons for their exclusions are provided in appendix K.
Summary of clinical studies included in the evidence review
Summaries of the studies that were included in this review are presented in Table 2 to Table 8.
See the full evidence tables in appendix D and forest plots in appendix E.
Summary of the evidence
No evidence regarding monotherapy or first-line therapies were identified in this review. Amongst the second-line interventions identified, add-on lamotrigine, add-on rufinamide, add-on high-dose and medium-dose clobazam, add-on topiramate and add-on felbamate showed important differences when compared with placebo; and add-on high-dose and medium-dose clobazam showed important differences when compared with low-dose clobazam. The majority of the evidence from these studies was very low to moderate quality, with most outcomes being seriously imprecise and at risk of bias due to lack of information regarding randomisation and allocation concealment.
For instance, add-on lamotrigine was associated with clinically important benefits in relation to reduction in seizure frequency >50%, and reduction in drop attacks when compared to placebo; add-on rufinamide was associated with clinically important benefits in relation to reduction in seizure frequency >50%, improvement in seizure severity, reduction in drop attacks and reduction in tonic seizures when compared to placebo; add-on high-dose and medium-dose clobazam were associated with reduced seizure frequency when compared to lodose clobazam. Finally, add-on topiramate was associated with clinically important reductions in seizure frequency >50%, and complete reduction in drop attacks when compared with placebo; and add-on felbamate was associated with clinically important benefis in relation to mean reduction of seizure frequency (all, atonic, generalised tonic-clonic) and quality of life when compared to placebo.
No clinically important differences were found for add-on rufinamide versus any other add-on antiseizure medication (note that only paediatric patients were included) and add-on low dose clobazam versus placebo.
No evidence was found for the following antiseizure therapies: sodium valproate, clonazepam, ethosuximide, levetiracetam, zonisamide, lacosamide, carbamazepine, gabapentin, oxcarbazepine, pregabalin, tiagabine, vigabatrin and ketogenic diet.
Quality assessment of clinical outcomes included in the evidence review
See the clinical evidence profiles in appendix F.
Economic evidence
Included studies
Two relevant papers were identified in the literature review of published economic evidence on this topic (Benedict 2010; Verdian 2010; see appendix H and appendix I for summary and full evidence tables). Both papers considered the cost effectiveness of rufinamide compared to topiramate and lamotrigine as an adjunctive treatment in children with Lennox-Gastaut syndrome. Benedict 2010 also included standard therapy alone as a comparator.
Both papers were also included in evidence report L, as these economic analyses were relevant for both topic areas of the guideline (Benedict 2010; Verdian 2010). Data relevant to evidence report L are reported in this evidence report.
Excluded studies
A single economic search was undertaken for all topics included in the scope of this guideline. See supplementary material 2 for details.
Summary of studies included in the economic evidence review
Benedict 2010 was a cost effectiveness analysis which reported outcomes in terms of cost per 1% increase in successfully treated patients in terms of tonic-atonic (drop attack) frequency and cost per 1% increase in successfully treated patients in terms of total number of seizures. Success was defined as a greater than 50% reduction in frequency compared to the baseline.
Verdian 2010 was a cost utility analysis which reported outcomes in terms of incremental cost per QALY. Utility values were estimated using time trade off methodology from 119 members of the UK general population.
Both studies adopted the perspective of the NHS & PSS. Both studies received funding from the manufacturer of rufinamide.
Economic model
No economic modelling was undertaken for this review because the committee agreed that other topics were higher priorities for economic evaluation.
Evidence statements
- There was evidence from 1 UK cost effectiveness analysis showing rufinamide cost an extra £62 and £2151 per 1% reduction in drop attacks and total seizures respectively compared to lamotrigine, topiramate andstandard therapy in children with Lennox-Gastaut syndrome. It was deemed partially applicable to the decision problem because whilst it took a UK NHS & PSS perspective it did not report outcomes in terms of quality adjusted life years (QALYs). It was deemed to have potentially serious methodological limitations as there was a lack of transparency around some parameters. It was deemed directly applicable to the decision problem but was deemed to have potentially serious methodological limitations.
- There was evidence from 1 UK cost utility model comparing rufinamide ith lamotrigine and topiramate in children with Lennox_Gastaut syndrome. The study estimated a cost per QALY for RUF of £20,538 and £154,831 compared to TPM and LTG respectively. There was a 52% and 8% probability that RUF was cost effective at a £20,000 per QALY threshold.
Summary of the economic evidence
Two economic evaluations relevant to the decision problem were identified (Benedict 2010, Verdian 2010).
Benedict 2010 was a patient simulation model comparing rufinamide (RUF) to lamotrigine (LTG), topiramate (TPM) and standard therapy in children with Lennox-Gastaut syndrome (LGS). It was deemed partially applicable to the decision problem because whilst it took a UK NHS & PSS perspective it did not report outcomes in terms of quality adjusted life years (QALYs). It was deemed to have potentially serious methodological limitations as it was funded by the manufacturer of RUF and there was a lack of transparency around some parameters. The study presented 2 analyses one considering reduction in drop attacks and the other reduction in total seizures. RUF was associated with a £62 cost per 1% reduction in drop attacks (compared to TPM) and £2151 per reduction in total seizures (compared to LTG). There was an 80% probability that RUF was the optimal treatment when willingness to pay for a 1% reduction in drop attacks and total seizures was £250 and £900 respectively.
Verdian 2010 was a Markov model comparing RUF to LMG and TPM as an adjunctive treatment in children with LGS. It was deemed directly applicable to the decision problem as it took a NHS & PSS perspective and reported outcomes in terms of cost per QALY. It was deemed to have potentially serious methodological limitations due to being funded by the manufacturer of RUF and lack of transparency around estimates of key parameters. The study estimated a cost per QALY for RUF of £20,538 and £154,831 compared to TPM and LTG respectively. There was a 52% and 8% probability that RUF was cost effective at a £20,000 per QALY threshold compared to TPM and LTG respectively. See appendix H and appendix I for summary and full evidence tables.
The committee’s discussion of the evidence
Interpreting the evidence
The outcomes that matter most
The committee agreed that seizure freedom, reduction of seizure frequency >50%, and frequency of drop attacks should be critical outcomes for this review as reducing the incidence of seizures/drop attacks is considered to be the main objective of treatment in this population.
The committee also agreed that time to withdrawal of treatment or change of medication, and adverse effects should be included as critical outcomes to ensure that data on treatment acceptability and tolerability were included.
Health-related quality of life was identified as an important outcome as tonic and atonic seizures/drop attacks can have a significant impact on a person’s daily life as they can often cause injury.
The quality of the evidence
In order to ensure consistency with evidence report L on Lennox-Gastaut syndrome (because tonic and atonic seizures/drop attacks are a common feature in this syndrome), the committee agreed that it was appropriate to amend the protocol for this review to include a number of ASMs which they believe to also be of relevance in the treatment of people with tonic or atonic seizures/drop attacks. These were: carbamazepine, clobazam, clonazepam, gabapentin, lacosamide, oxcarbazepine, pregabalin, tiagabine, vigabatrin.
The review did not identify any evidence relating specifically to tonic or atonic seizures/drop attacks, except in the context of Lennox-Gastaut syndrome. However, the committee agreed that it was appropriate to use these data as the basis for their recommendations as people with Lennox-Gastaut experience tonic or atonic seizures. The committee were presented with data on 9 different comparisons relating to 5 different treatments; however, meta-analysis was only possible for 2 comparisons.
The quality of the evidence for this review was assessed using GRADE methodology. The majority of outcomes were considered very low, low or moderate quality indicating uncertainly in the reliability of the data. Outcomes were most often downgraded due to risk of bias, with limited information provided regarding randomisation and allocation concealment. Outcomes were also downgraded due to imprecision arising as a result of small sample sizes and low event rates; which further limited confidence in the data.
Despite the lack of direct evidence from studies including population based on seizure type, the committee decided not to prioritise a research recommendation on this subject as they considered that other topics were of higher priority.
Benefits and harms
The committee considered the evidence included within this evidence review and used their expertise to make recommendations.
Tonic or atonic seizures/drop attacks cause muscle contractions that affect the whole body and cause loss of consciousness. Given the difficulties in treating tonic or atonic seizures/drop attacks, the range of syndromes of which they can feature and the impact that these can have on quality of life, the committee agreed to recommend that people who experience tonic and atonic seizures/drop attacks should be assessed by a neurologist with expertise in epilepsy with the aim of facilitating diagnosis, improving access to further investigations, and ensuring that appropriate treatment is provided. An appropriate diagnosis and timely treatment is key in preventing future seizures, which can have long-term consequences for the person, such as memory problems or severe injuries due to unpredictable sudden collapse to the floor or being thrown forwards or backwards. The involvement of a neurologist with expertise in epilepsy in the care of people with tonic or atonic seizures/drop attacks is standard current practice, therefore the committee did not think this recommendation would lead to increased costs or resource use.
The committee agreed that, prior to starting antiseizure therapy there should be a discussion with the person, their family and carers, if appropriate, about an individualised strategy according to their seizure type, treatment goals and the preferences of the person and their family or carers, as appropriate. Treatment plans should be regularly reassessed, and its agreement should include a transparent explanation of the epilepsy type, severity and duration of adverse effects that the person with epilepsy may experience and how should these be managed. The person, their family and carers, should also be made aware that they should be taking the least amount of medicines as possible to be effective due to the side effects of being on numerous medications.
Tonic or atonic seizures are classified as generalised seizures. Based on the evidence reviewed in evidence report E on monotherapy for generalised tonic-clonic seizures, and given the absence of evidence of effective monotherapy treatments in this review, the committee agreed that sodium valproate was the most effective medication for treating myoclonic seizures and that this was also generally accepted across clinical practice. The committee acknowledged the risks associated with sodium valproate if prescribed to women and girls who are able to have children and, as a result, recommended that lamotrigine should be used as first-line treatment in this population. There was some evidence that, when used as an add-on therapy, lamotrigine reduces seizure frequency, and the committee agreed that it was appropriate to extrapolate from this as lamotrigine is widely used in clinical practice for tonic or atonic seizures/drop attacks. Nonetheless, the committee all agreed that in some cases, for example, if women have tried other medication and it has not worked, sodium valproate should be available as an option. The committee agreed that sodium valproate should only be prescribed after a full and clear discussion with the girl or woman, ensuring she understands all the potential risks and benefits. If sodium valproate is prescribed, clinicians must follow MHRA guidance, which includes enrolment in a pregnancy prevention programme, if appropriate.
Based on the available evidence, which showed that add-on lamotrigine reduced seizure frequency when compared to placebo, the committee recommended lamotrigine as the first add-on treatment to sodium valproate if seizures continue in boys, men and women who are unable to have children. Based on their experience and expertise, the committee also recommended lamotrigine as second-line alternative treatment if sodium valproate was not successful. Although there was no evidence assessing the effectiveness of lamotrigine as monotherapy, the committee agreed that it was appropriate to extrapolate from the add-on evidence as lamotrigine is widely used in clinical practice for tonic or atonic seizures/drop attacks.
The evidence suggested that lamotrigine was as effective as clobazam when compared to placebo, however the committee recommended lamotrigine as second-line therapy in preference to clobazam because it is better tolerated. The committee also acknowledged that, due to the extended time required to titrate lamotrigine safely, clobazam is sometimes used in the short term to ameliorate seizures involving injuries. Once lamotrigine has reached adequate treatment doses, the decision to wean clobazam can be made on an individual basis.
The committee emphasised that, monotherapy should be used in the first instance. When starting alternative antiseizure medications, the dose of the new antiseizure medication should be slowly increased, whilst the existing antiseizure medication is tapered off. When starting an add-on antiseizure medications, the additional antiseizure medication should be carefully titrated, in line with the BNF guidance, adverse events monitored, and there should be a frequent treatment review.
There was also evidence which suggested that clobazam, rufinamide and topiramate are effective and the committee agreed that it was appropriate to recommend these as third-line add-on or alternative treatments. Clobazam is not licenced for children under 6 years old in the UK, but it can be on a named-patient basis. Although there was no evidence assessing the effectiveness of clobazam, rufinamide and topiramate as monotherapy treatment, the committee agreed that it was appropriate to extrapolate from the add-on evidence as these ASMs are commonly used in clinical practice for tonic or atonic seizures/drop attacks.
One of the studies assessing the effectiveness of clobazam conducted analysis by low-, medium- and high-dose, however the committee did not think that it was appropriate to recommend a specific dose of clobazam as this is decided on an individual basis. Furthermore, according to their clinical experience high doses of clobazam can worsen tonic seizures, although this is rare.
The review also included information relating to a small number of other ASMs, however as this evidence was generally of low quality and did not report head to head comparisons, the committee did not consider it was appropriate to recommend these. The committee noted that ketogenic diets are successfully used in clinical practice in cases which are difficult to treat and recommended these as a fourth-line treatment based on their expert opinion. The committee emphasised that these should only be prescribed under the guidance of a neurologist with expertise in epilepsy as these are calculated individually, and the person’s weight and ketone levels need to be monitored.
Felbamate was considered if all other treatment options for tonic or atonic seizures/drop attacks were not successful. Felbamate is not licensed in the UK but can be obtained on a named-patient basis and requires close monitoring for haematological and hepatic adverse effects associated with this drug. For these reasons the committee felt the use of felbamate required careful consideration by a neurologist with expertise in epilepsy.
Although no evidence was identified which reported on any of the other ASMs included in the protocol for this review the committee agreed that, whilst these may benefit some patients, clinical experience also suggests that they may exacerbate seizures. Therefore, they agreed to draft a recommendation stating this.
Cost effectiveness and resource use
The committee considered 2 previously published economic evaluations which considered rufinamide compared to lamotrigine and topiramate. The committee highlighted limitations with the evidence which prevented them making strong recommendations based upon it. Most significantly that both studies were funded by the manufacturer of rufinamide and the lack of transparency around key parameters. Both studies took a NHS & PSS perspective but one study did not report outcomes in terms of cost per QALY.
The committee also highlighted the age of the studies (>10 years) and that since these analyses were completed all drugs considered are now off patent and relatively inexpensive. It was therefore considered that the most effective treatment would also be the most cost effective. Given this and the identified weaknesses in the included economic evaluations recommendations were made in line with the clinical evidence.
The recommendations made for this review question are unlikely to change current practice and therefore no resource impact is anticipated.
Other factors the committee took into account
In line with the MHRA, the committee emphasised that long-term treatment with sodium valproate can cause decreased bone mineral density and increased risk of osteomalacia. The committee noted that appropriate supplementation should be considered for those at risk.
Recommendations supported by this evidence review
This evidence review supports recommendations 5.5.1-5.5.9.
References
Arzimanoglou 2019
Arzimanoglou A, Ferreira J, Satlin A, Olhaye O, Kumar D, Dhadda S, Bibbiani F. Evaluation of long-term safety, tolerability, and behavioral outcomes with adjunctive rufinamide in pediatric patients (≥ 1 to< 4 years old) with Lennox-Gastaut syndrome: Final results from randomized study 303. European Journal of Paediatric Neurology. 2019 Jan 1;23(1):126–35. [PubMed: 30309816]Benedict 2010
Benedict A, Verdian L, Maclaine G. The cost-effectiveness of rufinamide in the treatment of Lennox-Gastaut Syndrome in the UK. Pharmacoeconomics. 2010; 28(3):185–199. [PubMed: 20151724]Conry 2009
Conry JA, Ng YT, Paolicchi JM, Kernitsky L, Mitchell WG, Ritter FJ, Collins SD, Tracy K, Kormany WN, Abdulnabi R, Riley B. Clobazam in the treatment of Lennox-Gastaut syndrome. Epilepsia. 2009 May;50(5):1158–66. [PubMed: 19170737]Dodson 1993
Dodson WE. Felbamate in the treatment of Lennox-Gastaut syndrome: results of a 12-month open-label study following a randomized clinical trial. Epilepsia. 1993 Dec;34:S18–24. [PubMed: 8243374]Felbamate study group 1993
Felbamate Study Group in Lennox-Gastaut Syndrome. Efficacy of felbamate in childhood epileptic encephalopathy (Lennox-Gastaut syndrome). New England Journal of Medicine. 1993 Jan 7;328(1):29–33. [PubMed: 8347179]Glauser 2008
Glauser T, Kluger G, Sachdeo R, Krauss G, Perdomo C, Arroyo S. Rufinamide for generalized seizures associated with Lennox–Gastaut syndrome. Neurology. 2008 May 20;70(21):1950–8. [PubMed: 18401024]Motte 1997
Motte J, Trevathan E, Arvidsson JF, Barrera MN, Mullens EL, Manasco P, Lamictal Lennox–Gastaut Study Group. Lamotrigine for generalized seizures associated with the Lennox–Gastaut syndrome. New England Journal of Medicine. 1997 Dec 18;337(25):1807–12. [PubMed: 9400037]Ng 2011
Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA. Randomized, phase III study results of clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11;77(15):1473–81. [PubMed: 21956725]Ohtsuka 2014
Ohtsuka Y, Yoshinaga H, Shirasaka Y, Takayama R, Takano H, Iyoda K. Rufinamide as an adjunctive therapy for Lennox–Gastaut syndrome: a randomized double-blind placebo-controlled trial in Japan. Epilepsy research. 2014 Nov 1;108(9):1627–36. [PubMed: 25219353]Sachdeo 1999
Sachdeo RC, Glauser TA, Ritter FO, Reife R, Lim P, Pledger G, Topiramate YL Study Group. A double-blind, randomized trial of topiramate in Lennox–Gastaut syndrome. Neurology. 1999 Jun 1;52(9):1882-. [PubMed: 10371538]Verdian 2010
Verdian L, Yunni Y. Cost-utility analysis of rufinamide versus topiramate and lamotrigine for the treatment of children with Lennox-Gastaut Syndrome in the United Kingdom. Seizure. 2010; 19(1):1–11. [PubMed: 19942457]
Appendices
Appendix A. Review protocols
Review protocol for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (239K)
Appendix B. Literature search strategies
Literature search strategies for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (185K)
Appendix C. Clinical evidence study selection
Clinical study selection for: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (119K)
Appendix D. Clinical evidence tables
Clinical evidence tables for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (325K)
Appendix E. Forest plots
Forest plots for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (134K)
Appendix F. GRADE tables
GRADE tables for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (341K)
Appendix G. Economic evidence study selection
Economic evidence study selection for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information
Appendix H. Economic evidence tables
Economic evidence tables for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (179K)
Appendix I. Economic evidence profiles
Economic evidence profiles for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Download PDF (160K)
Appendix J. Economic analysis
Economic evidence analysis for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
No economic analysis was conducted for this review question.
Appendix K. Excluded studies
Excluded clinical and economic studies for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
Clinical studies
Table 22Excluded studies and reasons for their exclusion
Study | Reason for exclusion |
---|---|
Arnold, S., Badalamenti, V., Diaz, A., Gasalla, T., McShea, C., Whitesides, J., Fakhoury, T., Conversion to brivaracetam monotherapy for the treatment of patients with focal seizures: Two double-blind, randomized, multicenter, historical control, Phase III studies, Epilepsy Research, 141, 73–82, 2018 [PubMed: 29486396] | Does not report on atonic/tonic/drop group specifically - sample were people with focal seizures, focal epilepsy or epileptic syndrome group |
Arroyo, S., Dodson, W. E., Privitera, M. D., Glauser, T. A., Naritoku, D. K., Dlugos, D. J., Wang, S., Schwabe, S. K., Twyman, R. E., Randomized dose-controlled study of topiramate as first-line therapy in epilepsy, Acta Neurologica Scandinavica, 112, 214–222, 2005 [PubMed: 16146489] | Does not report on atonic/tonic/drop group specifically - only reports on generalised onset tonic-clonic and partial onset seizure groups |
Auvin, S., Williams, B., McMurray, R., Kumar, D., Perdomo, C., Malhotra, M., Novel seizure outcomes in patients with Lennox-Gastaut syndrome: Post hoc analysis of seizure-free days in rufinamide Study 303, Epilepsia Open, 4, 275–280, 2019 [PMC free article: PMC6546073] [PubMed: 31168494] | Unplanned post hoc analysis |
Balagura, G., Riva, A., Marchese, F., Verrotti, A., Striano, P., Adjunctive rufinamide in children with lennox-gastaut syndrome: A literature review, Neuropsychiatric Disease and Treatment, 16, 369–379, 2020 [PMC free article: PMC7008198] [PubMed: 32103957] | Does not report on atonic/tonic/drop group specifically except in the context of Lennox-Gastaut syndrome. All randomised studies included in this paper have been included in review 3.11 |
Baulac, M., Leon, T., O’Brien, T. J., Whalen, E., Barrett, J., A comparison of pregabalin, lamotrigine, and placebo as adjunctive therapy in patients with refractory partial-onset seizures, Epilepsy Research, 91, 10–9, 2010 [PubMed: 20696552] | Does not report on atonic/tonic/drop group specifically - focuses on partial seizure group only |
Benbadis, S., Klein, P., Schiemann, J., Diaz, A., Elmoufti, S., Whitesides, J., Efficacy, safety, and tolerability of brivaracetam with concomitant lamotrigine or concomitant topiramate in pooled Phase III randomized, double-blind trials: A posthoc analysis, Epilepsy & Behavior, 80, 129–134, 2018 [PubMed: 29414542] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures |
Ben-Menachem, E., Clinical efficacy of topiramate as add-on therapy in refractory partial epilepsy: The European experience, Epilepsia, 38, S28–S30, 1997 [PubMed: 9092955] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary GTC seizures |
Ben-Menachem, E., Mameniskiene, R., Quarato, P. P., Klein, P., Gamage, J., Schiemann, J., Johnson, M. E., Whitesides, J., McDonough, B., Eckhardt, K., Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies, Neurology, 87, 314–23, 2016 [PMC free article: PMC4955277] [PubMed: 27335114] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary GTC seizures. |
Beran, R. G., Berkovic, S. F., Dunagan, F. M., Vajda, F. J. E., Danta, G., Black, A. B., Mackenzie, R., Double-blind, placebo-controlled, crossover study of lamotrigine in treatment-resistant generalised epilepsy, Epilepsia, 39, 1329–1333, 1998 [PubMed: 9860069] | Does not report on atonic/tonic/drop group specifically - sample were people with generalised epilepsy as manifested by seizure patterns of absences, myoclonus, or tonic- clonic seizures or a combination of these |
Berkovic, S. F., Knowlton, R. C., Leroy, R. F., Schiemann, J., Falter, U., Placebo-controlled study of levetiracetam in idiopathic generalized epilepsy, Neurology, 69, 1751–1760, 2007 [PubMed: 17625106] | Does not report on atonic/tonic/drop group specifically - only reports on people with idiopathic generalized epilepsies group. NB Some of the sample are described at baseline as epxeriencing tonic seizures |
Besag, F. M. C., Wallace, S. J., Dulac, O., Alving, J., Spencer, S. C., Hosking, G., Lamotrigine for the treatment of epilepsy in childhood, Journal of Pediatrics, 127, 991–997, 1995 [PubMed: 8523205] | Trials on which analysis is based were not randomised/comparative |
Beydoun, A., Sackellares, J. C., Shu, V., Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: A double-blind, concentrationresponse design clinical trial, Neurology, 48, 182–188, 1997 [PubMed: 9008516] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
Biton, V., Di Memmo, J., Shukla, R., Lee, Y. Y., Poverennova, I., Demchenko, V., Saiers, J., Adams, B., Hammer, A., Vuong, A., Messenheimer, J., Adjunctive lamotrigine XR for primary generalized tonic-clonic seizures in a randomized, placebo-controlled study, Epilepsy and Behavior, 19, 352–358, 2010 [PubMed: 20937567] | Does not report on atonic/tonic/drop group specifically - sample were people with primary GTC |
Biton, V., Krauss, G., Vasquez-Santana, B., Bibbiani, F., Mann, A., Perdomo, C., Narurkar, M., A randomized, double-blind, placebocontrolled, parallel-group study of rufinamide as adjunctive therapy for refractory partial-onset seizures, Epilepsia, 52, 234–42, 2011 [PubMed: 20887365] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures. with/without secondary generalisation |
Biton, V., Montouris, G. D., Ritter, F., Riviello, J. J., Reife, R., Lim, P., Pledger, G., A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures, Neurology, 52, 1330–1337, 1999 [PubMed: 10227614] | Does not report on atonic/tonic/drop group specifically - sample were people with primary GTC (at baseline atonic/tonic seizures and drop attacks were recorded) |
Biton, V., Sackellares, J. C., Vuong, A., Hammer, A. E., Barrett, P. S., Messenheimer, J. A., Double-blind, placebo-controlled study of lamotrigine in primary generalized tonic-clonic seizures, Neurology, 65, 1737–1743, 2005 [PubMed: 16344515] | Does not report on atonic/tonic/drop group specifically - sample were people with primary GTC |
Biton, V., Shneker, B. F., Naritoku, D., Hammer, A. E., Vuong, A., Caldwell, P. T., Messenheimer, J. A., Long-term tolerability and safety of lamotrigine extended-release: Pooled analysis of three clinical trials, Clinical Drug Investigation, 33, 359–364, 2013 [PubMed: 23475541] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures and primary GTC |
Bonnett, L. J., Smith, C. T., Donegan, S., Marson, A. G., Treatment outcome after failure of a first antiepileptic drug, Neurology, 83, 552–560, 2014 [PMC free article: PMC4142004] [PubMed: 24994842] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without SG, GTC, absence, myoclonic, absence or myoclonic with TC, TC |
Bonnett, L. J., Smith, C. T., Smith, D., Williamson, P. R., Chadwick, D., Marson, A. G., Time to 12-month remission and treatment failure for generalised and unclassified epilepsy, Journal of Neurology, Neurosurgery and Psychiatry, 85, 603–610, 2014 [PMC free article: PMC4033033] [PubMed: 24292995] | Does not report on atonic/tonic/drop group specifically - sample were people with GTC, absence, myoclonic or absence seizures |
Bonnett, Lj, Powell, Ga, Tudur, Smith C, Marson, Ag, Breakthrough seizures-Further analysis of the Standard versus New Antiepileptic Drugs (SANAD) study, Plos one, 12, e0190035, 2017 [PMC free article: PMC5739445] [PubMed: 29267375] | Does not report on atonic/tonic/drop group specifically - sample were people with partial with/without secondary generalisation, absence, myoclonic or absence seizures with tonic- clonic seizures |
Brandl, U., Kurlemann, G., Neubauer, B., Rettig, K., Schauble, B., Schreiner, A., Seizure and cognitive outcomes in children and adolescents with epilepsy treated with topiramate, Neuropediatrics, 41, 113–20, 2010 [PubMed: 20859829] | Not comparative |
Bresnahan, R., Panebianco, M., Marson, A. G., Lamotrigine add-on therapy for drug-resistant generalised tonic-clonic seizures, Cochrane Database of Systematic Reviews, 2020 (7) (no pagination), 2020 [PMC free article: PMC7387132] [PubMed: 32609387] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Briant, R. H., Foote, S. E., Wallis, W. E., Sodium valproate (Epilim) in epilepsy: a trial, New Zealand Medical Journal, 88, 479–82, 1978 [PubMed: 105332] | Does not report on atonic/tonic/drop group specifically |
Brigo, F., Igwe, S. C., Bragazzi, N. L., Lattanzi, S., Clonazepam monotherapy for treating people with newly diagnosed epilepsy, Cochrane Database of Systematic Reviews, 2019 [PMC free article: PMC6863099] [PubMed: 31742671] | Does not report data on participants who experience atonic or tonic/drop seizures/attacks |
Brodie, M. J., Whitesides, J., Schiemann, J., D’Souza, J., Johnson, M. E., Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies, Epilepsy Research, 127, 114–118, 2016 [PubMed: 27589414] | Does not report on atonic/tonic/drop group specifically - sample were people with focal seizures with/without secondary generalisation |
Chandra, B., First seizure in adults: to treat or not to treat, Clinical Neurology & Neurosurgery, 94 Suppl, S61–3, 1992 [PubMed: 1320521] | Does not report on atonic/tonic/drop group specifically - sample were people with tonic-clonic and partial seizures |
Christensen, J., Andreasen, F., Poulsen, J. H., Dam, M., Randomized, concentration-controlled trial of topiramate in refractory focal epilepsy, Neurology, 61, 1210–8, 2003 [PubMed: 14610122] | Does not report on atonic/tonic/drop group specifically - focuses on simple partial seizures and complex partial seizures, with or without secondary generalization groups |
Chung, S. S., Hogan, R. E., Blatt, I., Lawson, P. B., Nguyen, H., Clark, A. M., Anders, B., Halvorsen, M. B., Prevail Ole Study Group, Long-term safety and sustained efficacy of USL255 (topiramate extended-release capsules) in patients with refractory partial-onset seizures, Epilepsy & Behavior, 59, 13–20, 2016 [PubMed: 27084978] | Not comparative |
Coppola, G., Caliendo, G., Veggiotti, P., Romeo, A., Tortorella, G., De Marco, P., Pascotto, A., Topiramate as add-on drug in children, adolescents and young adults with Lennox-Gastaut syndrome: an Italian multicentric study, Epilepsy Research, 51, 147–53, 2002 [PubMed: 12350390] | Not comparative |
Coppola, G., Capovilla, G., Montagnini, A., Romeo, A., Spano, M., Tortorella, G., Veggiotti, P., Viri, M., Pascotto, A., Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian multicenter open trial, Epilepsy Research, 49, 45–8, 2002 [PubMed: 11948006] | Not comparative |
Crawford, P., Chadwick, D., A comparative study of progabide, valproate, and placebo as add-on therapy in patients with refractory epilepsy, Journal of Neurology Neurosurgery and Psychiatry, 49, 1251–1257, 1986 [PMC free article: PMC1029073] [PubMed: 3098923] | Does not report on atonic/tonic/drop group specifically - sample were people with severe, partial or generalised |
Cross, J. H., Epilepsy (generalised seizures), BMJ clinical evidence, 2015 [PMC free article: PMC4400652] [PubMed: 25882687] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without, generalised, progressive myoclonic |
Cross, J. H., Auvin, S., Patten, A., Giorgi, L., Safety and tolerability of zonisamide in paediatric patients with epilepsy, European Journal of Paediatric Neurology, 18, 747–758, 2014 [PubMed: 25128350] | Does not report on atonic/tonic/drop group specifically - sample were people with generalised epilepsy |
Dodson, W. E., Kamin, M., Kraut, L., Olson, W. H., Wu, S. C., Topiramate titration to response: analysis of individualized therapy study (TRAITS), Annals of Pharmacotherapy, 37, 615–20, 2003 [PubMed: 12708932] | Not comparative |
Dooley, M., Plosker, G. L., Levetiracetam. A review of its adjunctive use in the management of partial onset seizures, Drugs, 60, 871–93, 2000 [PubMed: 11085199] | Narrative overview. References checked |
Dozieres-Puyravel, B., Auvin, S., An evidencebased review on the use of perampanel for the treatment of focal-onset seizures in pediatric patients, Neuropsychiatric Disease and Treatment, 15, 2789–2798, 2019 [PMC free article: PMC6767767] [PubMed: 31576134] | Does not report on atonic/tonic/drop group specifically - only reports on focal onset seizure group |
Duron, R. M., Medina, M. T., Martinez-Juarez, I. E., Bailey, J. N., Perez-Gosiengfiao, K. T., Ramos-Ramirez, R., Lopez-Ruiz, M., Alonso, M. E., Ortega, R. H. C., Pascual-Castroviejo, I., Machado-Salas, J., Mija, L., Delgado-Escueta, A. V., Seizures of idiopathic generalized epilepsies, Epilepsia, 46, 34–47, 2005 [PubMed: 16302874] | Narrative overview. References checked |
Fang, Y., Wu, X., Xu, L., Tang, X., Wang, J., Zhu, G., Hong, Z., Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types, Journal of Clinical Neuroscience, 21, 55–62, 2014 [PubMed: 24231559] | Does not report on atonic/tonic/drop group specifically - sample were people with partial and generalised seizures |
Faught, E., Sachdeo, R. C., Remler, M. P., Chayasirisobhon, S., Iragui-Madoz, V. J., Ramsay, R. E., Sutula, T. P., Kanner, A., Harner, R. N., Kuzniecky, R., Kramer, L. D., Kamin, M., Rosenberg, A., Felbamate monotherapy for partialonset seizures: An active-control trial, Neurology, 43, 688–692, 1993 [PubMed: 8469323] | Does not report on atonic/tonic/drop group specifically - focuses on partial-onset seizures with or without secondarily generalized seizures |
Freeman,J.M., The ketogenic diet: additional information from a crossover study, Journal of Child Neurology, 24, 509–512, 2009 [PubMed: 19189929] | Not randomised |
French, J. A., Costantini, C., Brodsky, A., von Rosenstiel, P., N. Study Group, Adjunctive brivaracetam for refractory partial-onset seizures: a randomized, controlled trial, Neurology, 75, 519–25, 2010 [PubMed: 20592253] | Does not report on atonic/tonic/drop group specifically - focuses on patients with POS (secondarily generalised/not secondarily generalised |
French, J. A., Gil-Nagel, A., Malerba, S., Kramer, L., Kumar, D., Bagiella, E., Time to prerandomization monthly seizure count in perampanel trials, Neurology, 84, 2014–2020, 2015 [PMC free article: PMC4442101] [PubMed: 25878175] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
French, J. A., Gil-Nagel, A., Malerba, S., Kramer, L., Kumar, D., Bagiella, E., Time to prerandomization monthly seizure count in perampanel trials: A novel epilepsy endpoint, Neurology, 84, 2014–20, 2015 [PMC free article: PMC4442101] [PubMed: 25878175] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
French, J. A., Krauss, G. L., Biton, V., Squillacote, D., Yang, H., Laurenza, A., Kumar, D., Rogawski, M. A., Adjunctive perampanel for refractory partial-onset seizures: Randomized phase III study 304, Neurology, 79, 589–596, 2012 [PMC free article: PMC3413761] [PubMed: 22843280] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
French, J. A., Krauss, G. L., Wechsler, R. T., Wang, X. F., Diventura, B., Brandt, C., Trinka, E., O’Brien, T. J., Laurenza, A., Patten, A., Bibbiani, F., Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy, Neurology, 85, 950–957, 2015 [PMC free article: PMC4567458] [PubMed: 26296511] | Does not report on atonic/tonic/drop group specifically - sample were people with primary GTC and IGE. At baseline some participants are reported as having experienced atonic and tonic seizures but there are no results presented which relate specifically to these groups |
French, Ja, Krauss, Gl, Wechsler, Rt, Wang, Xf, DiVentura, B, Brandt, C, Trinka, E, O’Brien, Tj, Laurenza, A, Patten, A, et al.,, Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial, Neurology, 85, 950–957, 2015 [PMC free article: PMC4567458] [PubMed: 26296511] | Does not report on atonic/tonic/drop group specifically - sample were people with primary GTC and IGE. At baseline some participants are reported as having experienced atonic and tonic seizures but there are no results presented which relate specifically to these groups |
Garnett, W. R., Optimizing antiepileptic drug therapy in the elderly, Annals of Pharmacotherapy, 39, 1852–1860, 2005 [PubMed: 16189285] | Narrative overview. References checked |
Giorgi, L., Gomez, G., O’Neill, F., Hammer, A. E., Risner, M., The tolerability of lamotrigine in elderly patients with epilepsy, Drugs & Aging, 18, 621–30, 2001 [PubMed: 11587248] | Does not report on atonic/tonic/drop group specifically - focuses mainly on patients with complex partial seizures and primary generalised seizures. Included non randomised trials |
Giri, V. P., Giri, O. P., Khan, F. A., Kumar, N., Kumar, A., Haque, A., Valproic acid versus lamotrigine as first-line monotherapy in newly diagnosed idiopathic generalized tonic -Clonic seizures in adults - A randomized controlled trial, Journal of Clinical and Diagnostic Research, 10, FC01–FC04, 2016 [PMC free article: PMC5020233] [PubMed: 27630862] | Does not report on atonic/tonic/drop group specifically - focuses on people with idiopathic generalized tonic-clonic seizures |
Glauser, A. T., Dlugos, J. D., Dodson, E. W., Grinspan, A., Wang, S., Wu, S. C., Topiramate monotherapy in newly diagnosed epilepsy in children and adolescents, Journal of Child Neurology, 22, 693–699, 2007 [PubMed: 17641254] | Does not report on atonic/tonic/drop group specifically - focuses on people with partial or generalised onset seizures |
Glauser, T, Laurenza, A, Yang, H, Williams, B, Ma, T, Fain, R, Efficacy and tolerability of adjunct perampanel based on number of antiepileptic drugs at baseline and baseline predictors of efficacy: a phase III post-hoc analysis, Epilepsy research, 119, 34–40, 2016 [PubMed: 26656783] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
Glauser, T. A., Levisohn, P. M., Ritter, F., Sachdeo, R. C., Topiramate in Lennox-Gastaut syndrome: Open-label treatment of patients completing a randomized controlled trial, Epilepsia, 41, S86–S90, 2000 [PubMed: 10768308] | Open-label extension study; all participants received topiramate and no comparison group was included (excluded from L-G review) |
Gram, L., Bentsen, K. D., Valproate: an updated review, Acta Neurologica Scandinavica, 72, 129–39, 1985 [PubMed: 2931939] | Not empirical/narrative overview |
Hancock, E., Cross, H., Treatment of Lennox-Gastaut syndrome, Cochrane database of systematic reviews (Online), CD003277, 2003 [PubMed: 12917958] | Review - references checked |
Hellings, J. A., Barth, F. X., Logan, M., Cook-Wiens, G., Osorio, I., Reed, R. C., Overnight versus progressive conversion of multiple daily-dose divalproex to once-daily divalproex extended release: Which strategy is better tolerated by adults with intellectual disabilities?, Journal of Clinical Psychopharmacology, 29, 492–495, 2009 [PubMed: 19745651] | Data on epilepsy/seizure type are not presented |
Hemery, C., Ryvlin, P., Rheims, S., Prevention of generalized tonic-clonic seizures in refractory focal epilepsy: A meta-analysis, Epilepsia, 55, 1789–1799, 2014 [PubMed: 25182978] | Does not report on atonic/tonic/drop group specifically - sample were people with focal seizures with/without secondary generalisation |
Henriksen, O., Johannessen, S. I., Clinical and pharmacokinetic observations on sodium valproate - a 5-year follow-up study in 100 children with epilepsy, Acta Neurologica Scandinavica, 65, 504–23, 1982 [PubMed: 6810648] | Not comparative |
Hogan, R. E., Blatt, I., Lawson, B., Nagaraddi, V., Fakhoury, T. A., Anders, B., Clark, A. M., Laine, D., Halvorsen, M. B., Chung, S. S., Efficacy of once-daily extended-release topiramate (USL255): a subgroup analysis based on the level of treatment resistance, Epilepsy & Behavior, 41, 136–9, 2014 [PubMed: 25461205] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures |
Hoy, S. M., Topiramate Extended Release: A Review in Epilepsy, CNS Drugs, 30, 559–566, 2016 [PubMed: 27224993] | Narrative review. References checked |
Hoy, S. M., Brivaracetam: A Review in Partial-Onset (Focal) Seizures in Patients with Epilepsy, CNS Drugs, 30, 761–772, 2016 [PubMed: 27503181] | Narrative overview. References checked |
Ieiri, I., Hirata, K., Higuchi, S., Kojima, K., Ikeda, M., Yamada, H., Aoyama, T., Pharmacoepide-miological study on adverse reactions of antiepileptic drugs, Chemical & Pharmaceutical Bulletin, 40, 1280–8, 1992 [PubMed: 1394649] | Not comparative |
Kaminow, L., Schimschock, J. R., Hammer, A. E., Vuong, A., Lamotrigine monotherapy compared with carbamazepine, phenytoin, or valproate monotherapy in patients with epilepsy, Epilepsy & Behavior, 4, 659–66, 2003 [PubMed: 14698699] | Does not report on atonic/tonic/drop group specifically - people with any type of seizure were eligible |
Kerr, M. P., Baker, G. A., Brodie, M. J., A randomized, double-blind, placebo-controlled trial of topiramate in adults with epilepsy and intellectual disability: Impact on seizures, severity, and quality of life, Epilepsy and Behavior, 7, 472–480, 2005 [PubMed: 16140593] | Does not report on atonic/tonic/drop group specifically – included people with GTC, partial seizures only, partial seizures with generalisation, ‘other’ |
Khan, N., Shah, D., Tongbram, V., Verdian, L., Hawkins, N., The efficacy and tolerability of perampanel and other recently approved antiepileptic drugs for the treatment of refractory partial onset seizure: A systematic review and Bayesian network meta-analysis, Current Medical Research and Opinion, 29, 1001–1013, 2013 [PubMed: 23659562] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset with/without secondary generalisation |
Klein, P., Johnson, M. E., Schiemann, J., Whitesides, J., Time to onset of sustained >=50% responder status in patients with focal (partialonset) seizures in three phase III studies of adjunctive brivaracetam treatment, Epilepsia, 58, e21–e25, 2017 [PubMed: 27988967] | Does not report on atonic/tonic/drop group specifically - sample were people with focal seizures |
Kluger, G., Bauer, B., Role of rufinamide in the management of Lennox-Gastaut syndrome (childhood epileptic encephalopathy), Neuropsychiatric Disease and Treatment, 3, 3–11, 2007 [PMC free article: PMC2654531] [PubMed: 19300535] | Narrative overview. References checked |
Ko, D., Yang, H., Williams, B., Xing, D., Laurenza, A., Perampanel in the treatment of partial seizures: Time to onset and duration of most common adverse events from pooled Phase III and extension studies, Epilepsy and Behavior, 48, 45–52, 2015 [PubMed: 26057204] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures |
Kothare, S., Kluger, G., Sachdeo, R., Williams, B., Olhaye, O., Perdomo, C., Bibbiani, F., Dosing considerations for rufinamide in patients with Lennox-Gastaut syndrome: Phase III trial results and real-world clinical data, Seizure, 47, 25–33, 2017 [PubMed: 28284045] | Systematic review which reports data from observational studies (excluded from L-G review) |
Krauss, G. L., Efficacy and tolerability of the new antiepileptic drugs I: treatment of new onset epilepsy: report of the Therapeutics and Technology Assessment Subcommittee and Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy Society, Neurology, 64, 172–4; author reply 172–4, 2005 [PubMed: 15645538] | Letter/commentary |
Krauss, G. L., Perucca, E., Kwan, P., Ben-Menachem, E., Wang, X. F., Shih, J. J., Patten, A., Yang, H., Williams, B., Laurenza, A., Final safety, tolerability, and seizure outcomes in patients with focal epilepsy treated with adjunctive perampanel for up to 4 years in an open-label extension of phase III randomized trials: Study 307, Epilepsia, 59, 866–876, 2018 [PubMed: 29574701] | Not comparative |
Krauss, G., Wechsler, R., Bibbiani, F., Patten, A., Williams, B., Yang, H., Gidal, B., Hussein, Z., Relationship between perampanel exposure, seizure outcomes and treatment-emergent adverse events (TEAEs) in patients with primary generalized tonic-clonic seizures (PGTCS): A randomized, double-blind (DB) phase III study, Neurology, 86, 2016 | Conference abstract |
Kwan, P., Mintzer, S., Laurenza, A., Patten, A., Cartwright, K., Evaluation of perampanel as monotherapy for focal seizures: Experience from open-label extension studies, Epilepsy and Behavior Case Reports, 9, 1–5, 2018 [PMC free article: PMC5916525] [PubMed: 29707476] | Does not report on atonic/tonic/drop group specifically - sample were people with focal with/without secondary generalisation and primary GTC |
Lee, S. K., Lee, S. A., Kim, D. W., Loesch, C., Pelgrims, B., Osakabe, T., Lee, B., N. study group, A randomized, open-label, multicenter comparative trial of levetiracetam and topiramate as adjunctive treatment for patients with focal epilepsy in Korea, Epilepsy & Behavior, 97, 67–74, 2019 [PubMed: 31195326] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Leppik, I. E., Yang, H., Williams, B., Zhou, S., Fain, R., Patten, A., Bibbiani, F., Laurenza, A., Analysis of falls in patients with epilepsy enrolled in the perampanel phase III randomized doubleblind studies, Epilepsia, 58, 51–59, 2017 [PubMed: 27869305] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
Leppik, I., Morrell, M., Godfroid, P., Arrigo, C., Seizure-free days observed in randomized placebo-controlled add-on trials with levetiracetam in partial epilepsy, Epilepsia, 44, 1350–2, 2003 [PubMed: 14510829] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures |
Machado, V. H., Palmini, A., Bastos, F. A., Rotert, R., Long-term control of epileptic drop attacks with the combination of valproate, lamotrigine, and a benzodiazepine: a ‘proof of concept,’ open label study, Epilepsia, 52, 1303–10, 2011 [PubMed: 21729037] | Not comparative |
Maguire, M., Marson, A. G., Ramaratnam, S., Epilepsy (generalised), Clinical Evidence, 20, 20, 2012 [PMC free article: PMC3635585] [PubMed: 22348419] | Does not report on atonic/tonic/drop group specifically - sample were people with generalised epilepsy (tonic clonic type) |
Maguire, M., Marson, A. G., Ramaratnam, S., Epilepsy (generalised), BMJ clinical evidence, 2010 [PMC free article: PMC3217650] [PubMed: 21418687] | Does not report on atonic/tonic/drop group specifically - sample were people with generalised epilepsies, partial onset, primary GTC |
Malhotra, M., Ngo, L. Y., Patten, A., Salah, A., Efficacy and safety of adjunctive perampanel in south korean patients with partial-onset seizures (POS) or primary generalized tonic-clonic seizures (PGTCS): Post hoc analysis of phase ii and III double-blind and open-label extension (OLEX) studies, Neurology. Conference: 72nd Annual Meeting of the American Academy of Neurology, AAN, 94, 2020 | Conference abstract |
Manitpisitkul, P., Shalayda, K., Todd, M., Wang, S. S., Ness, S., Ford, L., Pharmacokinetics and safety of adjunctive topiramate in infants (1-24 months) with refractory partial-onset seizures: A randomized, multicenter, open-label phase 1 study, Epilepsia, 54, 156–164, 2013 [PubMed: 23157581] | Does not report on atonic/tonic/drop group specifically – focused on infants with simple or complex partial onset seizures, with or without secondary generalization – but did include infants with tonic seizures although data on these children are not reported separately |
Marson, A. G., Maguire, M., Ramaratnam, S., Epilepsy, BMJ clinical evidence, 2009 [PubMed: 19445769] | Does not report on atonic/tonic/drop group specifically - sample were people with generalised (tonic clonic type |
McCormack, P. L., Rufinamide: a pharmacoeconomic profile of its use as adjunctive therapy in Lennox-Gastaut syndrome, Pharmacoeconomics, 30, 247–56, 2012 [PubMed: 22332960] | Cost-effectiveness/utility analysis only. Clinical results not included |
McDonald, T. J. W., Henry-Barron, B. J., Felton, E. A., Gutierrez, E. G., Barnett, J., Fisher, R., Lwin, M., Jan, A., Vizthum, D., Kossoff, E. H., Cervenka, M. C., Improving compliance in adults with epilepsy on a modified Atkins diet: A randomized trial, Seizure, 60, 132–138, 2018 [PubMed: 29960852] | Does not report on atonic/tonic/drop group specifically - sample were people with focal and generalised epilepsies |
McMurray, R., Striano, P., Treatment of Adults with Lennox-Gastaut Syndrome: Further Analysis of Efficacy and Safety/Tolerability of Rufinamide, Neurology and Therapy, 5, 35–43, 2016 [PMC free article: PMC4919131] [PubMed: 26861566] | Post-hoc analysis including a subgroup of adult patients (not pre-planned). Default NGA approach is not to include unplanned post-hoc analyses |
Messenheimer,J.A., Giorgi,L., Risner,M.E., The tolerability of lamotrigine in children, Drug Safety, 22, 303–312, 2000 [PubMed: 10789824] | Narrative overview. References checked |
Milovanovic, J. R., Jankovic, S. M., Pejcic, A., Milosavljevic, M., Opancina, V., Radonjic, V., Protrka, Z., Kostic, M., Evaluation of brivaracetam: a new drug to treat epilepsy, Expert Opinion on Pharmacotherapy, 18, 1381–1389, 2017 [PubMed: 28737479] | Narrative overview. References checked |
Mintzer, S., French, J., Williams, B., Patten, A., Laurenza, A., Extrapolation of Adjunctive Efficacy and Safety Data from Phase III Partial Epilepsy Trials to Evaluate Perampanel as Monotherapy, Neurology. Conference: 70th Annual Meeting of the American Academy of Neurology, AAN, 90, 2018 | Conference abstract |
Montouris, G., Yang, H., Williams, B., Zhou, S., Laurenza, A., Fain, R., Efficacy and safety of perampanel in patients with drug-resistant partial seizures after conversion from double-blind placebo to open-label perampanel, Epilepsy Research, 114, 131–40, 2015 [PubMed: 26088896] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures |
Moseley, B., Diaz, A., Elmoufti, S., Whitesides, J., Efficacy of adjunctive brivaracetam in patients with secondarily generalized tonic-clonic seizures at baseline: Pooled results from long-term follow-up studies, Neurology. Conference: 69th American Academy of Neurology Annual Meeting, AAN, 88, 2017 | Conference abstract |
Moseley, Bd, Sperling, Mr, Asadi-Pooya, Aa, Diaz, A, Elmouft, S, Schiemann, J, Whitesides, J, Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonicclonic seizures: pooled results from three Phase III studies, Epilepsy research, 127, 179–185, 2016 [PubMed: 27608437] | Does not report on atonic/tonic/drop group specifically - sample were people with focal seizures/SGTC |
Mullens, E. L., Clinical experience with lamotrigine monotherapy in adults with newly diagnosed epilepsy: A review of published randomised clinical trials, Clinical Drug Investigation, 16, 125–133, 1998 [PubMed: 18370530] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation and primary GTC |
Nct,, A Double-blind, Placebo-controlled Study of Levetiracetam in Epilepsy Patients With Generalized Tonic-clonic Seizures (Except Partial Seizures Evolving to Secondarily Generalized Seizures), Https: | Trial record (GTC population) |
Nevitt, S. J., Sudell, M., Tudur Smith, C., Marson, A. G., Topiramate versus carbamazepine monotherapy for epilepsy: an individual participant data review, Cochrane Database of Systematic Reviews, 2019 [PMC free article: PMC6590101] [PubMed: 31233229] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Nevitt, S. J., Sudell, M., Weston, J., Tudur Smith, C., Marson, A. G., Antiepileptic drug monotherapy for epilepsy: A network meta-analysis of individual participant data, Cochrane Database of Systematic Reviews, 2017 (6) (no pagination), 2017 [PMC free article: PMC6481892] [PubMed: 28661008] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures (simple partial, complex partial or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus) |
Nishida, T., Lee, S. K., Inoue, Y., Saeki, K., Ishikawa, K., Kaneko, S., Adjunctive perampanel in partial-onset seizures: asia-Pacific, randomized phase III study, Acta Neurologica Scandinavica, 137, 392–399, 2018 [PubMed: 29250772] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures |
Nishida, T., Lee, S. K., Wu, T., Tiamkao, S., Dash, A., Efficacy and safety of perampanel in generalized and focal to bilateral tonic-clonic seizures: A comparative study of Asian and non-Asian populations, Epilepsia, 60, 47–59, 2019 [PubMed: 30869168] | Does not report on atonic/tonic/drop group specifically - only reports on focal to bilateral tonicclonic and generalised tonic-clonic seizure groups |
Nolan, S. J., Sudell, M., Weston, J., Tudur Smith, C., Marson, A. G., Antiepileptic drug monotherapy for epilepsy: A network meta-analysis, Cochrane Database of Systematic Reviews, 2014 (12) (no pagination), 2014 [PMC free article: PMC6486134] [PubMed: 29243813] | Protocol for a review on partial onset and generalised onset TC seizures |
Novotny, E., Renfroe, B., Yardi, N., Nordli, D., Ness, S., Wang, S., Weber, T., Kurland, C. L., Yuen, E., Eerdekens, M., Venkatraman, L., Nye, J. S., Ford, L., Randomized trial of adjunctive topiramate therapy in infants with refractory partial seizures, Neurology, 74, 714–20, 2010 [PMC free article: PMC2836871] [PubMed: 20089937] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
Ohtsuka, Y., Yoshinaga, H., Shirasaka, Y., Takayama, R., Takano, H., Iyoda, K., Long-term safety and seizure outcome in Japanese patients with Lennox-Gastaut syndrome receiving adjunctive rufinamide therapy: An open-label study following a randomized clinical trial, Epilepsy Research, 121, 1–7, 2016 [PubMed: 26827266] | Open-label extension study; all participants received rufinamide and no comparison group was included (excluded from L-G review) |
Olsson, P., Reimers, A., Kallen, K., Quality of life after switching to generic levetiracetam - A prospective comparative study, Epilepsy and Behavior, 96, 169–174, 2019 [PubMed: 31150996] | Not randomised |
Ormrod, D., McClellan, K., Topiramate: A review of its use in childhood epilepsy, Paediatric Drugs, 3, 293–319, 2001 [PubMed: 11354701] | Narrative overview. References checked |
Pålhagen, S, Canger, R, Henriksen, O, van, Parys Ja, Rivière, Me, Karolchyk, Ma, Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy, Epilepsy research, 43, 115–124, 2001 [PubMed: 11164700] | Does not report on atonic/tonic/drop group specifically - sample were people with partial or primary generalised epilepsy |
Pellock, J., Carman, W., Thyagarajan, V., Daniels, T., Morris, D., D’Cruz, O., Determining antiepileptic drug efficacy in pediatric patients: Results from a systematic review of clinical trials in adults compared to children, Neurology. Conference: 64th American Academy of Neurology Annual Meeting. New Orleans, LA United States. Conference Publication:, 78, 2012 | Conference abstract |
Pohlmann-Eden, B., Marson, A. G., Noack-Rink, M., Ramirez, F., Tofighy, A., Werhahn, K. J., Wild, I., Trinka, E., Comparative effectiveness of levetiracetam, valproate and carbamazepine among elderly patients with newly diagnosed epilepsy: subgroup analysis of the randomized, unblinded KOMET study, BMC Neurology, 16, 149, 2016 [PMC free article: PMC4995751] [PubMed: 27552848] | Mixed population. No indication that sample included people with atonic/tonic seizures or drop attacks |
Ramsay, R. E., DeToledo, J., Tonic-clonic seizures: A systematic review of antiepilepsy drug efficacy and safety, Clinical Therapeutics, 19, 433–446, 1997 [PubMed: 9220208] | Does not report on atonic/tonic/drop group specifically - sample were people with GTC seizures |
Ramsay, R. E., Uthman, B., Pryor, F. M., Rowan, A. J., Bainbridge, J., Spitz, M., Sirven, J. I., Frederick, T. E., Topiramate in older patients with partial-onset seizures: a pilot double-blind, dose-comparison study, Epilepsia, 49, 1180–5, 2008 [PubMed: 18494791] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures |
Rektor, I., Krauss, G. L., Inoue, Y., Kaneko, S., Williams, B., Patten, A., Bibbiani, F., Laurenza, A., Wechsler, R. T., Assessment of the longterm efficacy and safety of adjunctive perampanel: Pooled analyses of four open-label extension studies, Neurology. Conference: 69th American Academy of Neurology Annual Meeting, AAN, 88, 2017 | Conference abstract |
Rektor, I., Krauss, G. L., Inoue, Y., Kaneko, S., Williams, B., Patten, A., Malhotra, M., Laurenza, A., Wechsler, R. T., Assessment of the longterm efficacy and safety of adjunctive perampanel in tonic-clonic seizures: Analysis of four open-label extension studies, Epilepsia, 61, 1491–1502, 2020 [PMC free article: PMC7497073] [PubMed: 32645213] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Richens, A., Yuen, A. W., Overview of the clinical efficacy of lamotrigine, Epilepsia, 32 Suppl 2, S13–16, 1991 [PubMed: 1837775] | Narrative overview. References checked |
Rosenfeld, W. E., Benbadis, S., Edrich, P., Tassinari, C. A., Hirsch, E., Levetiracetam as addon therapy for idiopathic generalized epilepsy syndromes with onset during adolescence: Analysis of two randomized, double-blind, placebo-controlled studies, Epilepsy Research, 85, 72–80, 2009 [PubMed: 19327967] | Does not report on atonic/tonic/drop group specifically - sample were people with idiopathic generalized epilepsy syndromes (JAE, JME or GTC on awakening) |
Rosenfeld, W., Conry, J., Lagae, L., Rozentals, G., Yang, H., Fain, R., Williams, B., Kumar, D., Zhu, J., Laurenza, A., Efficacy and safety of perampanel in adolescent patients with drugresistant partial seizures in three double-blind, placebo-controlled, phase III randomized clinical studies and a combined extension study, European Journal of Paediatric Neurology, 19, 435–45, 2015 [PubMed: 25823975] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures |
Rugg-Gunn, F., Adverse effects and safety profile of perampanel: a review of pooled data, Epilepsia, 55 Suppl 1, 13–5, 2014 [PubMed: 24400692] | Narrative overview. References checked |
Sachdeo, R. C., Reife, R. A., Lim, P., Pledger, G., Topiramate monotherapy for partial onset seizures, Epilepsia, 38, 294–300, 1997 [PubMed: 9070591] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures |
Sachdeo, R., Kramer, L. D., Rosenberg, A., Sachdeo, S., Felbamate monotherapy: Con- trolled trial in patients with partial onset seizures, Annals of Neurology, 32, 386–392, 1992 [PubMed: 1416808] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures |
Sander, J. W. A. S., Patsalos, P. N., Oxley, J. R., Hamilton, M. J., Yuen, W. C., A randomised double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy, Epilepsy Research, 6, 221–226, 1990 [PubMed: 2272345] | Does not report on atonic/tonic/drop group specifically - sample were people with partial and secondary generalised and generalised seizures |
Siegel, H., Kelley, K., Stertz, B., Reeves-Tyer, P., Flamini, R., Malow, B., Gaillard, W. D., Ko, D., Theodore, W. H., The efficacy of felbamate as add-on therapy to valproic acid in the Lennox-Gastaut syndrome, Epilepsy Research, 34, 91–97, 1999 [PubMed: 10210023] | Not randomised |
Slater, J., Chung, S., Huynh, L., Duh, M. S., Gorin, B., McMicken, C., Ziemann, A., Isojarvi, J., Efficacy of antiepileptic drugs in the adjunctive treatment of refractory partial-onset seizures: Meta-analysis of pivotal trials, Epilepsy Research, 143, 120–129, 2018 [PubMed: 29784458] | Does not report on atonic/tonic/drop group specifically - samples were people with partial onset seizures |
Smith, C. T., Marson, A. G., Chadwick, D. W., Williamson, P. R., Multiple treatment comparisons in epilepsy monotherapy trials, Trials, 8 (no pagination), 2007 [PMC free article: PMC2194733] [PubMed: 17983480] | Does not report on atonic/tonic/drop group specifically - sample were people with partial and generalised onset seizures |
Smith, D., Baker, G., Davies, G., Dewey, M., Chadwick, D. W., Outcomes of add-on treatment with lamotrigine in partial epilepsy, Epilepsia, 34, 312–322, 1993 [PubMed: 8453943] | Does not report on atonic/tonic/drop group specifically - sample were people with partial epilepsy with/without secondary generalised seizures |
Steinhoff, B. J., Adjunctive perampanel for partial-onset seizures, Acta Neurologica Scandinavica, 137, 376–377, 2018 [PubMed: 29527673] | Editorial |
Tallian, K. B., Nahata, M. C., Tsao, C. Y., Role of the ketogenic diet in children with intractable seizures, Annals of Pharmacotherapy, 32, 349–61, 1998 [PubMed: 9533066] | Narrative overview. References checked |
Thibault, M., Blume, W. T., Saint-Hilaire, J. M., Zakhari, R., Sommerville, K. W., Divalproex extended-release versus the original divalproex tablet: results of a randomized, crossover study of well-controlled epileptic patients with primary generalized seizures, Epilepsy Research, 50, 243–249, 2002 [PubMed: 12200215] | Does not report on atonic/tonic/drop group specifically - sample were people with generalised epilepsy. Included people who experienced tonic seizures but results are not reported separately |
Tian, X., Yuan, M., Zhou, Q., Wang, X., The efficacy and safety of brivaracetam at different doses for partial-onset epilepsy: a meta-analysis of placebo-controlled studies, Expert Opinion on Pharmacotherapy, 16, 1755–67, 2015 [PubMed: 26165169] | Does not report on atonic/tonic/drop group specifically. Sample comprised of people with partial onset seizures |
Tjia-Leong, E., Leong, K., Marson, A., Lamotrigine add-on for refractory generalized tonic-clonic seizures, Cochrane Database of Systematic Reviews, (4) (no pagination), 2009 [PubMed: 21154386] | Protocol for a review on GTC |
Tjia-Leong, E., Leong, K., Marson, A. G., Lamotrigine adjunctive therapy for refractory generalized tonic-clonic seizures, Cochrane database of systematic reviews (Online), 12, CD007783, 2010 [PubMed: 21154386] | Does not report on atonic/tonic/drop group specifically - sample were people with with primary generalized epilepsy (this is, experiencing myoclonic epilepsy, generalized epilepsy with tonic clonic seizures on awakening and other idiopathic seizures). Studies involving participants with absence epilepsy and Lennox Gastaut syndrome were excluded |
Tomson, T., Hirsch, L. J., Friedman, D., Bester, N., Hammer, A., Irizarry, M., Ishihara, L., Krishen, A., Spaulding, T., Wamil, A., Leadbetter, R., Sudden unexpected death in epilepsy in lamotrigine randomized-controlled trials, Epilepsia, 54, 135–140, 2013 [PubMed: 23030403] | Includes partial and generalised seizures. Results for generalised seizures are reported separately and authors state that this includes tonic seizures |
Trinka, E., Tsong, W., Toupin, S., Patten, A., Wilson, K., Isojarvi, J., James, D., A systematic review and indirect treatment comparison of perampanel versus brivaracetam as adjunctive therapy in patients with focal-onset seizures with or without secondary generalization, Epilepsy Research, 166 (no pagination), 2020 [PubMed: 32673969] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Tsai, J. J., Ikeda, A., Hong, S. B., Likasitwattanakul, S., Dash, A., Efficacy, safety, and tolerability of perampanel in Asian and non-Asian patients with epilepsy, Epilepsia, 60, 37–46, 2019 [PubMed: 30869165] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Vadney, V. J., Kraushaar, K. W., Effects of switching from Depakene to generic valproic acid on individuals with mental retardation, Mental Retardation, 35, 468–72, 1997 [PubMed: 9425876] | Type of epilepsy/seizures not reported. States only that participants had seizure disorders |
Vadney, V., Ricketts, R. W., Cole, R. W., Effects on individuals with mental retardation of changing Depakote to Depakene, Mental Retardation, 32, 341–6, 1994 [PubMed: 7984119] | Not comparative |
Verrotti, A., Loiacono, G., Ballone, E., Mattei, P. A., Chiarelli, F., Curatolo, P., Efficacy of rufinamide in drug-resistant epilepsy: A meta-analysis, Pediatric Neurology, 44, 347–349, 2011 [PubMed: 21481742] | Does not report on atonic/tonic/drop group specifically - appears to only focus on L-G. Relevant study (Glauser, 2008) is included in L-G review |
Villanueva, V., Majid, O., Nabangchang, C., Yang, H., Laurenza, A., Ferry, J., Hussein, Z., Pharmacokinetics, exposure-cognition, and exposure-efficacy relationships of perampanel in adolescents with inadequately controlled partialonset seizures, Epilepsy research, 127, 126–134, 2016 [PubMed: 27595590] | Does not report on atonic/tonic/drop group specifically - sample were people with partial onset seizures with/without secondary generalised |
Vining, E. P., Botsford, E., Freeman, J. M., Valproate sodium in refractory seizures: a study of efficacy, American Journal of Diseases of Children, 133, 274–6, 1979 [PubMed: 371384] | Does not report on atonic/tonic/drop group specifically |
Vossler, D. G., Zonisamide as adjunctive therapy for adults with partial- onset epileptic seizures: An efficacy and safety review, Clinical Medicine Insights: Therapeutics, 2, 331–339, 2010 | Narrative overview. References checked |
Wang, Y., Zhou, D., Wang, B., Kirchner, A., Hopp, P., Kerling, F., Pauli, E., Stefan, H., Clinical effects of topiramate against secondarily generalized tonic-clonic seizures, Epilepsy Research, 49, 121–130, 2002 [PubMed: 12049800] | Does not report on tonic/atonic/drop population specifically (focuses on people with partial seizures and SGTC) but does report on improvements in ‘tonic signs’ Comparison is low vs high dose |
Wechsler, R. T., Leroy, R., Van Cott, A., Hammer, A. E., Vuong, A., Huffman, R., Van- Landingham, K., Messenheimer, J. A., Lamotrigine extended-release as adjunctive therapy with optional conversion to monotherapy in older adults with epilepsy, Epilepsy Research, 108, 1128–36, 2014 [PubMed: 24888248] | Not comparative |
Wheless, J. W., Use of topiramate in childhood generalized seizure disorders, Journal of Child Neurology, 15, S7–S13, 2000 [PubMed: 11218056] | Narrative overview |
Wheless, J. W., Levetiracetam in the treatment of childhood epilepsy, Neuropsychiatric Disease and Treatment, 3, 409–421, 2007 [PMC free article: PMC2655081] [PubMed: 19300570] | Narrative overview. References checked |
Wisniewski, C. S., Rufinamide: A new antiepileptic medication for the treatment of seizures associated with Lennox-Gastaut syndrome, Annals of Pharmacotherapy, 44, 658–667, 2010 [PubMed: 20233912] | Narrative overview. References checked |
Wu, L., Yagi, K., Hong, Z., Liao, W., Wang, X., Zhou, D., Inoue, Y., Ohtsuka, Y., Sasagawa, M., Terada, K., Du, X., Muramoto, Y., Sano, T., Adjunctive levetiracetam in the treatment of Chinese and Japanese adults with generalized tonic-clonic seizures: A double-blind, randomized, placebo-controlled trial, Epilepsia Open, 3, 474–484, 2018 [PMC free article: PMC6276779] [PubMed: 30525116] | Does not report on atonic/tonic/drop group specifically - only reports on generalised tonic-clonic seizure group. Although at baseline some patients reported that they had experienced atonic/tonic seizures |
Xiao, Z., Li, J. M., Wang, X. F., Xiao, F., Xi, Z. Q., Lv, Y., Sun, H. B., Efficacy and safety of levetiracetam (3,000 mg/Day) as an adjunctive therapy in Chinese patients with refractory partial seizures, European Neurology, 61, 233–9, 2009 [PubMed: 19176965] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures with/without secondary generalisation |
Xu, Z., Zhao, H., Chen, Z., The efficacy and safety of rufinamide in drug-resistant epilepsy: A meta-analysis of double-blind, randomized, placebo controlled trials, Epilepsy Research, 120, 104–110, 2016 [PubMed: 26811934] | Only reports on atonic/tonic/drop group as part of the Lennox-Gastuat population. Not reported as a subgroup. The relevant study (Glauser, 2008) has been included in the NGA Lennox-Gastaut review |
Zaccara, G., Giovannelli, F., Cincotta, M., Verrotti, A., Grillo, E., The adverse event profile of perampanel: meta-analysis of randomized controlled trials, European Journal of Neurology, 20, 1204–11, 2013 [PubMed: 23607817] | Does not report on atonic/tonic/drop group specifically - sample were people with partial epilepsy or Parkinsons disease |
Zhang, L., Huang, J., Zhuang, J. H., Huang, L. Q., Zhao, Z. X., Topiramate as an adjunctive treatment for refractory partial epilepsy in the elderly, Journal of International Medical Research, 39, 408–15, 2011 [PubMed: 21672344] | Does not report on atonic/tonic/drop group specifically - sample were people with partial epilepsy |
Zhang, Y., Xu, J., Zhang, K., Yang, W., Li, B., The Anticonvulsant Effects of Ketogenic Diet on Epileptic Seizures and Potential Mechanisms, Current Neuropharmacology, 16, 66–70, 2018 [PMC free article: PMC5771386] [PubMed: 28521671] | Narrative overview |
Zhao, T., Feng, X., Liu, J., Gao, J., Zhou, C., Evaluate the Efficacy and Safety of Anti-Epileptic Medications for Partial Seizures of Epilepsy: A Network Meta-Analysis, Journal of Cellular Biochemistry, 118, 2850–2864, 2017 [PubMed: 28214290] | Does not report on atonic/tonic/drop group specifically - sample were people with partial seizures |
Zhou S, Zhan Q, Wu X; Effect of levetiracetam on cognitive function and clonic seizure frequency in children with epilepsy, Current Molecular Medicine, 2019 [PubMed: 31362674] | Does not include participants who experience drop or tonic/atonic seizures and does not report on these as an outcome |
Economic studies
A global search of economic evidence was undertaken for all review questions in this guideline. See Supplement 2 for further information
Appendix L. Research recommendations
Research recommendations for review question: What antiseizure therapies (monotherapy or add-on) are effective in the treatment of tonic or atonic seizures/drop attacks?
No research recommendations were made for this review question.
Final
Evidence reviews underpinning recommendations 5.5.1-5.5.9 in the NICE guideline
These evidence reviews were developed by the National Guideline Alliance which is part of the Royal College of Obstetricians and Gynaecologists
Disclaimer: The recommendations in this guideline represent the view of NICE, arrived at after careful consideration of the evidence available. When exercising their judgement, professionals are expected to take this guideline fully into account, alongside the individual needs, preferences and values of their patients or service users. The recommendations in this guideline are not mandatory and the guideline does not override the responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or their carer or guardian.
Local commissioners and/or providers have a responsibility to enable the guideline to be applied when individual health professionals and their patients or service users wish to use it. They should do so in the context of local and national priorities for funding and developing services, and in light of their duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a way that would be inconsistent with compliance with those duties.
NICE guidelines cover health and care in England. Decisions on how they apply in other UK countries are made by ministers in the Welsh Government, Scottish Government, and Northern Ireland Executive. All NICE guidance is subject to regular review and may be updated or withdrawn.
- Supplement 1: Methods (PDF)
- NICE guideline: methods (PDF)
- Supplement 2: Health economics (PDF)
- Supplement 3: Cost effectiveness of antiseizure therapies for people with focal and generalised tonic-clonic seizures (PDF)
- Cost-utility analysis: The cost effectiveness of resective epilepsy surgery in adults (PDF)
- PubMedLinks to PubMed
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- Long-term outcome after callosotomy or vagus nerve stimulation in consecutive prospective cohorts of children with Lennox-Gastaut or Lennox-like syndrome and non-specific MRI findings.[Seizure. 2013]Long-term outcome after callosotomy or vagus nerve stimulation in consecutive prospective cohorts of children with Lennox-Gastaut or Lennox-like syndrome and non-specific MRI findings.Cukiert A, Cukiert CM, Burattini JA, Lima AM, Forster CR, Baise C, Argentoni-Baldochi M. Seizure. 2013 Jun; 22(5):396-400. Epub 2013 Mar 13.
- Review Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy.[Drugs. 1995]Review Lamotrigine. An update of its pharmacology and therapeutic use in epilepsy.Fitton A, Goa KL. Drugs. 1995 Oct; 50(4):691-713.
- Review Add-on therapy for generalised tonic-clonic and focal onset seizures: Epilepsies in children, young people and adults: Evidence review F[ 2022]Review Add-on therapy for generalised tonic-clonic and focal onset seizures: Epilepsies in children, young people and adults: Evidence review FNational Guideline Alliance (UK). 2022 Apr
- Review Monotherapy for generalised tonic-clonic and focal onset seizures: Epilepsies in children, young people and adults: Evidence review E[ 2022]Review Monotherapy for generalised tonic-clonic and focal onset seizures: Epilepsies in children, young people and adults: Evidence review ENational Guideline Alliance (UK). 2022 Apr
- Effectiveness of antiseizure therapies in the treatment of tonic or atonic seizu...Effectiveness of antiseizure therapies in the treatment of tonic or atonic seizures/drop attacks
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