***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: The Fifth Commission on Antiepileptic Drugs of the International League Against Epilepsy was asked to advise the ILAE Executive on the place of new drugs in the treatment of patients with newly diagnosed or chronic epilepsy . With the licensing of a significant number of new antiepileptic drugs ( AEDs ) in the last 5 - 10 years , there is an obvious need for these new treatments to be introduced efficiently and effectively to benefit the care and management of people with epilepsy . Implicit in this will be a determination of the comparative efficacy , tolerability , and overall effectiveness against st and ard ( existing ) AEDs and against other new drugs . Although many of the issues relating to comparative studies were addressed in Guidelines for the Clinical Evaluation of Antiepileptic Drugs , produced by the Fourth Commission , several complex ethical and method ological problems remain that would benefit from further discussion aim ed at the establishment of some form of consensus . Although determination of the relative risks of rare but potentially serious idiosyncratic adverse reactions and teratogenicity can be determined only by adequate postmarketing surveillance , other issues concerning the efficacy , tolerability , and effectiveness of new drugs can best be determined within the context of well- design ed r and omized ( or otherwise controlled ) clinical trials ( RCTs ) . It is the design , structure , and outcomes of such comparative RCTs that dem and further consideration . Many of the difficulties arise because the most meaningful and satisfactory comparative studies will essentially be those that compare monotherapy with a new agent with monotherapy with alternative agents . The Commission recognizes that several different parties have interests in comparative studies . First and foremost patients and their doctors require adequate information to guide daily practice in an “ evidence -based ” way so that patients can make fully informed decisions about their drug treatment . Individual pharmaceutical manufacturers need to know how their drug compares with other products so that a drug can be appropriately positioned in the market . Licensing authorities have traditionally ignored issues of comparative A benzodiazepine drug , clobazam , was evaluated in 14 refractory epileptic patients , nine of whom received the drug double-blind . Ten patients have been given  clobazam  long enough to assess results . Four showed marked benefit , four failed to respond and two showed a transient benefit which was maintained by dose changes of both clobazam and clonazepam .  Side effects were minimal ; doses ranged from 15 to 60 mg per day . Clobazam may have place in the treatment of the Lennox Gastaut syndrome and other types of refractory seizures Objective To compare the effectiveness of intermittent clobazam versus diazepam therapy in preventing the recurrence of febrile seizures and assess adverse effects of each drug . Methods This prospect i ve r and omized controlled trial was performed on neurologically normal children aged from 6 months to 5 years with a history of simple febrile seizures and normal electroencephalogram without any evidence of acute central nervous system infection . The patients were r and omly prescribed with oral clobazam ( 37 cases ) or diazepam ( 35 cases ) when they developed a febrile disease . They were advised to use the medications during the first 48 h of the onset of fever . All the patients were monitored regarding developing seizure and adverse effects of the drugs . All patients were followed for 12 months . Results Overall , 243 episodes of fever occurred during the period , including 116 episodes in the clobazam group and 127 episodes in the diazepam group . Recurrence of seizures occurred in 2 ( 1.7 % ) subjects in the clobazam group , and in 4(3.1 % ) cases in the diazepam group . ( P value = 0.474 ) . Twenty cases ( 54 % ) in the diazepam group and 5 ( 14.2 % ) cases in the clobazam group developed drowsiness and sedation during the follow-up period ( P value = 0.0001 ) . Conclusions Intermittent clobazam therapy seems advantageous to diazepam due to similar efficacy but significantly lower adverse effects such as drowsiness and sedation BACKGROUND It is now agreed that the prognosis of seizure disorder due to solitary cysticercus granuloma ( SCG ) is generally good . However , the choice antiepileptic drugs ( AEDs ) remain empirical , with no comparative trials of different AEDs being available . AIMS To determine the safety and efficacy ( measured by the incidence of ' treatment failure ' ) of clobazam in comparison to st and ard treatment with phenytoin-sodium for prevention of seizures in persons with solitary cysticercus granulomas ( SCGs ) . SETTING S AND DESIGN This pilot study was conducted in a neurology department of a medical college hospital in the form of a prospect i ve , r and omized , open-labeled trial . MATERIAL S AND METHODS Forty-eight patients with seizures due to SCG were r and omized in an open-labeled trial to either , clobazam ( 1 mg/kg oral loading followed by 0.5 mg/kg/d ) ( n=21 ) or phenytoin ( 15 mg/kg , oral loading in 3 divided doses over 24 h , followed by 5 mg/kg/d ) ( n=27 ) . They were followed over 6 months with the primary outcome measure being treatment failure ( either discontinuation or modification of AEDs ) due to either adverse effects or breakthrough seizures . RESULTS Treatment failures were noted to be significantly less common ( P = 0.03 ) in the clobazam-treated group ( n=1 ; 4.7 % ) than in phenytoin-treated group ( n=9 ; 33.3 % ) . These included one patient ( 4.7 % ) in the clobazam-group who had breakthrough seizures and 3 ( 11.1 % ) who had breakthrough seizures and 6 ( 22.2 % ) in the phenytoin-treated group who had adverse effects requiring treatment discontinuation . CONCLUSIONS Clobazam was well tolerated , safe and more effective than phenytoin in the AED treatment of patients with SCG Clobazam was compared with placebo as antiepileptic adjunct medication in 129 therapy-resistant epileptic patients who were mainly suffering from complex partial seizures . The study was performed in five European countries according to a double-blind crossover design lasting 7 months . Two treatment periods of 3 months ( 1 month adjustment and 2 months maintenance medication ) were separated by one medication switch-over month . The difference in seizure reduction between clobazam and placebo was significant ( p less than 0.05 ) . Nineteen percent of patients receiving clobazam became seizure-free during the maintenance dose period . In contrast , freedom from seizures was not observed in any placebo patient . Electroencephalogram ( EEG ) signs , mood ratings , and global impressions also indicated therapeutic effects of clobazam in epilepsy . The most frequent adverse reactions to clobazam were drowsiness and dizziness . However , the sedative effects of clobazam seemed to be less pronounced in comparison with other benzodiazepines . The study gives evidence of the therapeutic value of clobazam as adjunct medication in therapy-resistant partial seizures . The use of clobazam as monotherapy and long-term treatment , as well as the particular seizure response pattern to clobazam , has to be further investigated The effect of 1,5-benzodiazepine clobazam was assessed in a double-blind add-on trial in 20 patients with chronic complex partial seizures uncontrolled by maximally tolerable daily dosage of st and ard antiepileptic drug therapy .  The number of seizures was lower during the three months of active treatment . At the end of the third month , eight ( 40 % ) of the patients had a seizure reduction by more than 75 % , including four patients ( 20 % ) who had complete control . Tolerance to the antiepileptic effect of clobazam was noted in 56 % of the patients , and mild transient sedation occurred in 40 % of the patients . Despite these drawbacks , clobazam is an effective add-on drug for individual patients with refractory focal epilepsy The cyclical exacerbations of epilepsy ( catamenial epilepsy ) were used to assess the antiepileptic effect of a benzodiazepine , clobazam . Doses of 20 mg , and in some cases 30 mg , per day were compared with placebo over predetermined ten-day periods in a double-blind cross-over study . The results were evaluated by preference in a sequential procedure . In 14 of 18 patients who received both treatments  clobazam was superior to placebo , and in 4 patients no preference was established . Clobazam completely prevented seizures in most of the patients , and toxic effects were of low frequency and severity Clobazam , 20 or 30 mg/day was given for 10 days around menstruation in successive menstrual cycles to 13 women who had responded favourably to this drug in an earlier short-term placebo controlled cross-over study . Three patients have been successfully treated , with complete freedom from seizures around menstruation , for 3 - 3 1/2 years and two others responded favourably until pregnancy made treatment inappropriate . A further four patients did well during a shorter period ( 6 - 13 months ) of follow-up . An increase in seizures between periods of clobazam therapy was observed in three patients , and led to the withdrawal of this drug in two of them . However , tolerance to the antiepileptic effect of clobazam was not observed in any patient , even though nine were treated for 1 year or more . In only once case was it necessary to discontinue treatment because of sedative side effects Clobazam is a benzodiazepine with special molecular structure ( its nitrogen radicals are in positions 1 and 5 , rather than 1 and 4 as in all other antiepileptic benzodiazepines ) , and it is rapidly effective -- in a matter of hours or within a few days -- against all varieties of epileptic seizures in 52 % of subjects treated with it . Its effects are relatively mild . Unfortunately , its outst and ing antiepileptic properties are exhausted after only a few weeks in one-third of all cases . The authors discuss the potential significance of this phenomenon , and stress the urgent need for intensive study of the basic mechanism governing exhaustion of the antiepileptic properties of the benzodiazepines in general and clobazam in particular Objective : To evaluate the efficacy of intermittent clobazam therapy in preventing the recurrence of febrile seizures and to assess its safety . Methods : The study was a prospect i ve , r and omized , double-blind placebo-controlled trial conducted in the Department of Child Health , Christian Medical College Hospital , Vellore between July 2001 and September 2002 . Neurologically normal children between 6 months and 3 years of age with a history of febrile seizures and no evidence of acute CNS infection or EEG abnormality were included into the study . 19 children in a clobazam group and 20 in the placebo group were r and omly allocated .  Temperature reduction measures with paractamol and tepid sponging were advised to all children . In addition the dispensed medication was to be administered at the onset of fever and continued for 48 hours irrespective of the duration of fever . The children were then monitored for seizures and adverse effects of clobazam . The children were followed up for a mean period of 9.9 months . The analysis was done on the number of febrile episodes in both the groups . Results : There were a total of 110 episodes of fever during the study period . Mean number of febrile episodes in the clobazam group was 3.1 and in placebo group 2.56 . Six ( 12.5 % ) of the 48 episodes in placebo group and one ( 1.7 % ) of 60 episodes in clobazam group had seizure recurrence . This was statistically significant ( p=0.01 ) . Drowsiness and weakness were present equally in both clobazam and placebo group whereas ataxia was present only in the clobazam group , the difference being statistically significant ( p=0.04 ) . Conclusion : Intermittent clobazam therapy is an effective measure in the prevention of recurrence of febrile seizures . The ataxia due to clobazam was much lower than that reported with diazepam PURPOSE To compare the cognitive and behavioural effects of clobazam versus st and ard monotherapy in the treatment of childhood epilepsy . METHODS A r and omized , double-blind , prospect i ve design was carried out at three Canadian pediatric epilepsy centres . This study was part of a larger multi-centre study on the efficacy of clobazam .  Children with newly diagnosed epilepsy were assigned r and omly to receive clobazam or carbamazepine .  Children who had failed previous treatment with carbamazepine  were assigned r and omly to clobazam or phenytoin .  Children who had failed on any other antiepileptic drug were assigned r and omly to receive clobazam or carbamazepine . In a subset of patients neuropsychological assessment s were carried out at 6 weeks and 12 months after initiation of medication . Intelligence , memory , attention , psychomotor speed , and impulsivity were assessed . RESULTS There were no differences between the clobazam and st and ard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months . There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period . CONCLUSION The cognitive and behavioural effects of clobazam appear to be similar to those of st and ard monotherapy 
    Output:
    
We found no advantage for clobazam over carbamazepine for retention at 12 months in drug-naïve children and a slight advantage of clobazam over phenytoin for retention at six months in adolescents and adults with neurocysticercosis in a single clinical trial each .