***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Objective : To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy ( CAE ) . Methods : The Child Behavior Checklist ( CBCL ) was administered at baseline , week 16–20 , and month 12 visits of a r and omized double-blind trial of ethosuximide , lamotrigine , and valproate . Total problems score was the primary outcome measure . Results : A total of 382 participants at baseline , 310 participants at the week 16–20 visit , and 168 participants at the month 12 visit had CBCL data . At baseline , 8 % ( 95 % confidence interval [ CI ] 6%–11 % ) of children with CAE had elevated total problems scores ( mean 52.9 ± 10.91 ) . At week 16–20 , participants taking valproic acid had significantly higher total problems ( 51.7 [ 98.3 % CI 48.6–54.7 ] ) , externalizing problems ( 51.4 [ 98.3 % CI 48.5–54.3 ] ) , attention problems ( 57.8 [ 98.3 % CI 55.6–60.0 ] ) , and attention-deficit/hyperactivity problems ( 55.8 [ 98.3 % CI 54.1–57.6 ] ) scores compared to participants taking ethosuximide ( 46.5 [ 98.3 % CI 43.4–49.6 ] ; 45.8 [ 98.3 % CI 42.9–48.7 ] ; 54.6 [ 98.3 % CI 52.4–56.9 ] ; 53.0 [ 98.3 % CI 51.3–54.8 ] ) . Lack of seizure freedom and elevated week 16–20 Conner Continuous Performance Test confidence index were associated with worse total problems scores . At month 12 , participants taking valproic acid had significantly higher attention problems scores ( 57.9 [ 98.3 % CI 55.6–60.3 ] ) compared to participants taking ethosuximide ( 54.5 [ 95 % CI 52.1–56.9 ] ) . Conclusions : Pretreatment and ongoing behavioral problems exist in CAE . Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine , further reinforcing ethosuximide as the preferred initial therapy for CAE . Clinical trials.gov identifier : NCT00088452 . Classification of evidence : This study provides Class II evidence that for children with CAE , valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine Summary : One hundred twenty children aged 10 months to 16 years 9 months were included in three studies with lamotrigine ( LTG ) : a single‐blind study ( n = 60 ) , a pharmacokinetic study ( n = 23 ) , and a compassionate group ( n = 37 ) . At 3 months , 11 patients had become seizure‐free and 34 had > 50 % decrease in seizure frequency . The best results involved absence epilepsy , Lennox‐Gastaut syndrome ( LGS ) , and other symptomatic generalized epilepsy . Forty‐two patients were followed > 1 year , 22 for a mean of 2.2 years , and there was no significant increase in seizure frequency as compared with 3‐month follow‐up . Fourteen patients became seizure‐free for > 6 months ; all except 1 had generalized epilepsy . For 12 patients , treatment could be reduced to monotherapy , but for those with valproate ( VPA ) comedication  LTG  dosage had to be increased ; 25 % of patients with VPA monotherapy exhibited skin rash , appearing 3–18 days after starting LTG . For 4 patients , LTG could be reintroduced after VPA was withdrawn . Ten patients had ataxia and /or drowsiness and 2 had vomiting . For all other patients , tolerance was excellent The aim of the present study was to verify the clinical efficacy of melatonin ( MLT ) in children , adolescents and young adults with wake-sleep disorder and mental retardation , most of them on chronic anticonvulsant therapy for epileptic seizures , by means of a r and omized , double-blind , placebo-controlled cross-over trial . Twenty-five patients ( 16 males , nine females ) , aged from 3.6 to 26 years ( mean 10.5 years ) , all affected with mental retardation mostly with epileptic seizures , were r and omized to oral synthetic fast-release MLT or placebo . Melatonin was initiated at the daily dose of 3 mg , at nocturnal bedtime . In case of inefficacy , MLT dose could be titrated up to 9 mg the following 2 weeks at increments of 3 mg/week , unless the patient was unable to tolerate it . The analysis of all the sleep logs disclosed a significant treatment effect of melatonin on sleep latency ( P = 0.019 ) . Melatonin was well tolerated in all patients and no side effects were reported . In conclusion , our study supports the efficacy of MLT in young patients with mental disabilities and epileptic seizures in improving the wake-sleep disorders such as time to fall asleep . Overall , MLT appeared to influence the seizure frequency poorly , though there may be occasional seizure worsening or improving . Such a dual effect requires further studies in young epileptic patients OBJECTIVE In this multicenter study , the efficacy and tolerability of lamotrigine were assessed in 285 children less than 13 years of age , recruited from 37 centers in 11 countries . METHODS Pooled data from five open add-on studies have been analyzed . All the children had treatment-resistant epilepsy and most had two or more seizure types .  Seizure frequency and global evaluation were assessed at the end of four successive 12-week periods of therapy . RESULTS Seizure frequency was reduced by 50 % or more in one third of the patients . Lamotrigine was effective in all seizure types examined , particularly for typical and atypical absence seizures . Atonic seizures also responded well . Improvement was well maintained during the treatment period . The maintenance dose had to be adjusted according to concomitant medication ; dose ranges were 1 to 5 mg/kg per day for children taking valproate and 5 to 15 mg/kg per day for those not taking valproate . The commonest reported adverse experiences were somnolence , rash , vomiting , and seizure exacerbations . Adverse experiences led to withdrawal of treatment from 36 patients ( 12.6 % ) . CONCLUSIONS These results indicate that lamotrigine is well tolerated and is effective for a broad range of seizure types , especially absence seizures and atonic seizures Summary Purpose To evaluate the efficacy , tolerability , and effects on behavior and psychosocial functioning of lamotrigine monotherapy in children with newly diagnosed typical absence seizures . Patients and methods Children meeting enrollment criteria ( n = 54 ) received a confirmatory 24-h ambulatory electroencephalogram ( EEG ) and then entered a Escalation Phase of up to 20-weeks during which lamotrigine was titrated until seizures were controlled or maximum dose ( 10.2 mg/kg ) was reached . Seizure freedom was assessed by diary review and clinic hyperventilation ( clinic HV ) and then confirmed by EEG with hyperventilation ( HV/EEG ) . Patients who maintained seizure freedom for two consecutive weekly visits were entered into the Maintenance Phase ( n = 30 ) .  Diary , clinic HV , and HV/EEG data were supplemented with  24-h ambulatory EEG  at baseline and the ends of the Escalation and Maintenance Phases . Health outcome assessment s were completed at screening and at the end of the Maintenance Phase . Results By the end of the Escalation Phase , seizure-free rates ( responders ) were 59 % by seizure diary ( n = 51 ) , 56 % by HV/EEG ( n = 54 ) ( primary endpoint ) , and 49 % by 24-h ambulatory EEG ( n = 49 ) . During the Maintenance Phase , 89 % ( week 24 ) and 86 % ( week 32 ) remained seizure free by diary ( n = 28 ) , 78 % by clinic HV ( n = 27 ) , and 81 % by 24-h ambulatory EEG ( n = 26 ) . Seizure freedom was first observed beginning at the fifth week of the Escalation Phase . The most frequent adverse events were headache and cough . Health outcome scores were either improved or unchanged at the end of the Maintenance Phase . Conclusions Lamotrigine monotherapy results in complete seizure freedom in a substantial number of children with typical absence seizures . Lamotrigine was well tolerated in this study OBJECTIVE To compare the efficacy of valproic acid ( VPA ) and lamotrigine as a monotherapy for absence epilepsy in children . METHODS A r and omized , open-label design was used . Childhood absence epilepsy was diagnosed based on the presence of typical seizures and video-EEG findings . Eligible patients were r and omly treated with VPA or lamotrigine . All patients were followed up for 12 months . RESULTS Forty-five out of 48 eligible children completed the study . There were 23 children in the VPA group and 22 children in the lamotrigine group . Seventeen children were seizure-free in the VPA group 12 months after treatment . Fifteen out of the 17 children showed normal EEG ( no epileptic-formed discharge ) . Twelve children were seizure-free in the lamotrigine group 12 months after treatment . The proportion showing normal EEG in the lamotrigine group ( 6/22 , 27.3 % ) was significantly lower than that in the VPA group ( 15/23 , 65.2 % ) ( P<0.05 ) . Severe adverse effects were not found in both groups . CONCLUSIONS Both VPA and lamotrigine are safe and efficacious for treatment of absence seizures in children .  VPA appears to be better than lamotrigine in tapering epileptic-formed discharge OBJECTIVE To explore the efficacy and safety of the combined therapy of valproic acid ( VPA ) and lamotrigine ( LTG ) for various types of epilepsy . METHODS The patients were recruited from the epilepsy center at Affiliated Tongji Hospital , Tongji Medical College , Huazhong Science & Technology University from January 2009 to September 2011 . They were r and omly selected through a number chart and divided into two groups : child group and adult group . The prospect i ve follow-up study lasted for one year to examine the long-term efficacy and safety of combined therapy . Seizure frequency was recorded at Months 3 , 6 and 12 . The changes of seizure frequency were analyzed to calculate the 50 % response rate , 75 % response rate and seizure-free rate . All side effects during therapy were recorded . The correlation of efficacy with seizure type was also examined . Statistical analysis was performed through t test , variance analysis and χ(2 ) test . RESULTS Among a total of 134 patients , 10 of them withdrew . At Months 3 , 6 and 12 , as compared with baseline , the average reduction rate of seizure frequency per month was 56 % , 62 % , 70 % in child group versus 74 % , 82 % , 85 % in adult group ( P < 0.05 ) . Adult group was better than child group . At Month 3 , 50 % response rate , 75 % response rate and seizure-free rate was 70.97 % - 35.48 % in child group versus 83.87 % - 43.01 % in adult group . When compared at Months 3 , 6 and 12 , 50 % response rate , 75 % response rate and seizure-free rate showed no statistical difference ( P > 0.05 ) . The worse outcomes occurred more frequently in the patients with complex partial seizure ( CPS ) and than those with simple partial seizure ( SPS ) and generalized seizure GS ( P < 0.05 ) . Rash was the major side effect for withdrawal . CONCLUSION The co-medication of VPA and LTG  is both effective and safe for all epileptic types , especially for SPS and GS . And the efficacy may last for up to one year . Combined therapy shows excellent safety PURPOSE To compare the efficacy of lamotrigine ( LTG ) and valproic acid ( VPA ) in newly diagnosed children and adolescents with typical absence seizures . METHODS A r and omized , open-label parallel-group design was used . After undergoing an awake video-EEG recording , which included one to two trials of 3 min of hyperventilation and intermittent photic stimulation , eligible patients were r and omized to receive LTG or VPA . LTG was initiated at a daily dose of 0.5 mg/kg for 2 weeks in two divided doses , followed by 1.0 mg/kg/day for an additional 2 weeks . Thereafter , doses were increased in 1-mg/kg/day increments every 5 days until seizures were controlled , intolerable adverse effects occurred , or a maximum dose of 12 mg/kg/day had been reached . VPA was equally uptitrated 
    Output:
    
There are no placebo-controlled trials for ethosuximide or valproate , and hence , no evidence from r and omised controlled trials to support a specific effect on absence seizures for either of these two drugs .
Overall , this large study demonstrates the superior effectiveness of ethosuximide and VPA compared to lamotrigine as initial monotherapy aim ed to control seizures without intolerable adverse effects in children with childhood absence epilepsy .
With regards to both efficacy and tolerability , ethosuximide represents the optimal initial empirical monotherapy for children and adolescents with absence seizures .
However , if absence and generalised tonic-clonic seizures coexist , valproate should be preferred , as ethosuximide is probably inefficacious on tonic-clonic seizures