Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.
Effectiveness of New Antiepileptic Drugs (AEDs) in Refractory Partial Epilepsy as Adjunctive Therapy
- It is appropriate to use gabapentin, lamotrigine, tiagabine, topiramate, oxcarbazepine, levetiracetam, and zonisamide as add-on therapy in patients with refractory epilepsy (Level A) (Please refer to the table below titled "Summary of American Academy of Neurology (AAN) Evidence-Based Guidelines Level A or B Recommendation for Use").
Note: In a previous AAN parameter, felbamate was recommended for "intractable partial seizures in patients over 18 years who had failed standard AEDs."
Effectiveness of New AEDs as Monotherapy in Patients with Refractory Partial Epilepsy
- Oxcarbazepine and topiramate can be used as monotherapy in patients with refractory partial epilepsy (Level A).
- Lamotrigine can be used as monotherapy in patients with refractory partial epilepsy (Level B, downgraded due to dropouts).
- There is insufficient evidence to recommend use of gabapentin, levetiracetam, tiagabine, or zonisamide in monotherapy for refractory partial epilepsy (Level U) (Please refer to the table below titled "Summary of AAN Evidence-Based Guidelines Level A or B Recommendation for Use").
Effectiveness of New AEDs in Patients with Refractory Idiopathic Generalized Epilepsy
- Topiramate may be used for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level A).
- There is insufficient evidence to recommend gabapentin, lamotrigine, oxcarbazepine, tiagabine, levetiracetam, or zonisamide for the treatment of refractory generalized tonic-clonic seizures in adults and children (Level U) (Please refer to the table below titled "Summary of AAN Evidence-Based Guidelines Level A or B Recommendation for Use").
Effectiveness of New AEDs in Refractory Partial Epilepsy as Adjunctive in Children
- Gabapentin, lamotrigine, oxcarbazepine, and topiramate may be used as adjunctive treatment of children with refractory partial seizures (Level A) (Please refer to the table below titled "Summary of AAN Evidence-Based Guidelines Level A or B Recommendation for Use").
- There is insufficient evidence to recommend levetiracetam, tiagabine, or zonisamide as adjunctive treatment of children with refractory partial seizures (Level U) (Please refer to the table below titled "Summary of AAN Evidence-Based Guidelines Level A or B Recommendation for Use").
Effectiveness of New AEDs as Mono-therapy in Children with Refractory Partial Seizures
No monotherapy trials have been performed in this population.
Effectiveness of New AEDs for Refractory Idiopathic Generalized Epilepsy in Children
Studies of topiramate and gabapentin in idiopathic generalized tonic-clonic convulsions already discussed above included children as well.
Effectiveness of New AEDs in Children and/or Adults with the Lennox-Gastaut Syndrome
- Topiramate and lamotrigine may be used to treat drop attacks associated with the Lennox Gastaut syndrome in adults and children (Level A) (Please refer to the table below titled "Summary of AAN Evidence-Based Guidelines Level A or B Recommendation for Use").
Note: In a previous AAN parameter, felbamate was recommended in "Lennox-Gastaut patients over age 4 unresponsive to primary AEDs."
Table: Summary of AAN Evidence-Based Guidelines Level A or B Recommendation for Use**
Drug |
Partial adjunctive adult |
Partial monotherapy |
Primary generalized |
Symptomatic generalized |
Pediatric partial |
Gabapentin |
Yes |
No |
No |
No |
Yes |
Lamotrigine |
Yes |
Yes |
No |
Yes |
Yes |
Topiramate |
Yes |
Yes* |
Yes (only generalized tonic-clonic) |
Yes |
Yes |
Tiagabine |
Yes |
No |
No |
No |
No |
Oxcarbazepine |
Yes |
Yes |
No |
No |
Yes |
Levetiracetam |
Yes |
No |
No |
No |
No |
Zonisamide |
Yes |
No |
No |
No |
No |
*Not Food and Drug Administration approved for this indication
**In a previous parameter, felbamate was recommended for intractable partial seizures in patients over age 18 and patients over 4 with the Lennox-Gastaut syndrome. Felbamate is associated with significant and specific risks, and risk-benefit ratio must be considered.
Definitions:
Rating of Recommendations
A = Established as effective, ineffective, or harmful for the given condition in the specified population.
B = Probably effective, ineffective, or harmful for the given condition in the specified population.
C = Possibly effective, ineffective, or harmful for the given condition in the specified population.
U = Data inadequate or conflicting; given current knowledge, treatment is unproven.
Translation of Evidence to Recommendations
Level A rating requires at least one convincing class I study or at least two consistent, convincing class II studies.
Level B rating requires at least one convincing class II study or at least three consistent class III studies.
Level C rating requires at least two convincing and consistent class III studies.
Rating of Therapeutic Article
Class I: Prospective, randomized, controlled clinical trial (RCT) with masked outcome assessment, in a representative population. The following are required:
- Primary outcome(s) is/are clearly defined.
- Exclusion/inclusion criteria are clearly defined.
- Adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias.
- Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
Class II: Prospective matched group cohort study in a representative population with masked outcome assessment that meets a–d above OR a RCT in a representative population that lacks one criterion a–d.
Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome assessment is independent of patient treatment.
Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.