After 12 months amantadine had the highest percentage free from treatment failure (79%).(Scott Perry). In Glauser et al. (2013) 53% treated with ethosuximide was free from treatment failure, 58% in valproic acid and 29 % in lamotrigine .
At 24 months ethosuximide had a free from failure rate of 75%, valproic acid had 67.8 and lamotrigine had 66.7. However there was no significant difference between the freedom- from- treatment failure rates for ethosuximide, lamotrigine and valproic acid.
The other drug therapy were not measured at 24 months.
The common reasons for treatment failure were lack of seizure control and intolerable side effects .
Drug therapy , onset and long-term effects
The follow-up ranged from 14 days to 2 years. The onset of efficacy was faster for Ethosuximide compared with valproic acid and lamotrigine( see follow up Gauser et al. 2010+2013)
The long-term treatment of ethosuximide , valproic acid and lamotrigine are equally effective.
Children treated with either ethosuximide of valproic acid had higher seizure free rates(respectively 87 and 75) than those treated with lamotrigine.(64)
The percentage seizure free in topiramate was lowest.(33)
Adverse events (see table 3)
All studies described types of adverse events after drug therapy.
A. Glauser et al. discovered the valproic acid cohort experienced a higher rate of adverse events than in the ethosuximide cohort. Attentional dysfunction was more common with valproic (49%) acid than with ethosuximide persisted at 12 months (33%) p=0,03. The increase in BMI was an adverse event leading to discontinuation of the treatment in the cohort of valproic.( glauser 2013).
Holmes et al. described headache and cough after using lamotrigine. About 10% of patients using lamotrigine has a significant risk of rashes , and therefore it is recommended to increase the dose very slow. This may decrease the patientsâ apllience.
The adverse events were lowest in amantadine and levetiractam. Topiramate was remarkably high.(67%)
The other drugs had no specific adverse events.
The onset of seizure control in ethosuximide is faster compared with valproic acid or lamotrigine. (7)Ethosuximide and valproic acid were more effective than lamotrigine, but ethosuximide resulted in fewer attentional effects as compared with valproic acid.
There were no significant differences among the three drugs with regard to discontinuation because of adverse events.
The long-term efficacy showed that ethosuximide, valproic acid and lamotrigine were equally efficacious. The newer drugs; levetiractam, amantadine and topiramate are also a possibility for treatment, but data is limited.
Overall the first choice drug therapy for children with absence seizures is ethosuximide.
Limitations and recommendations
Direct comparison of drugs was challenging because of the different study population, different study designs and relative small number of patients. Also the follow up time was different in the researches. This review considered only 12 months and 24 months follow up time to compare, with the exception of Fattore et al. in which the follow-up time was 14 days. This is quite short to determine a real effect.
Furthermore most studies contained information about the short-term follow-up( 1 year) except Hee Wang et al. In the future more trials are required to have especially the long-term follow- up to see the long-term adverse events, like chronic drug toxicities such as weight gain in valproic acid. It is also important in order to determine if the drug still is working. When children with absence seizures get older, there is an increased risk of generalized tonic- clonic seizures and ethosuximide has previously been reported to be limited in preventing these types of seizures. (4, 5, 7)
The newer drugs have possibly fewer side effects and are better tolerated than the older ones (ethosuximide), however few have been tested under rigorous conditions. Data of levetiractam, topiramate and amantadine is limited. Levetiractam is a promising drug, however there is little researched. The same applies for topiramate and amantadine. The number of patients was also small. The study of topiramate was early terminated because of the small sample size (n=12). The number of patients of amantadine was n =14.
The studies used different measure outcomes and also the definition of the outcomes were different. For example in Hee Wang et al. the definition of seizure free was not described.
In the future the outcome need to include : free from seizures, (EEG and clinical), an hyperventilation test, adverse events, psychosocial outcomes , cognitive outcome ( school performances) and attentional outcomes. There was no consideration for school performance in the studies, even though this is very relevant, because of the number of seizures a day.
Finally there almost none placebo controlled trials , and this is quite important to see an effect of a drug of AS. So at first all the drug has to be tested in placebo controlled trials and after that they have to be compared in RCTâs.