***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 
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    Input: 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 Clobazam is a 1,5-benzodiazepine effective in antiepileptic therapy of children and adults . Presently it is mainly used as adjuvant therapy for intractable seizures . Our objective was to evaluate the effect of clobazam on the apparent clearance of other antiepileptic drugs at steady state , and to determine the factors that determine the plasma levels of clobazam and its active metabolite N-desmethylclobazam . Patients were 74 children with intractable seizures who received treatment with clobazam at our institution as part of the Canadian Cooperative Clobazam Study Group during the years 1987 to 1991 . Serum concentrations of clobazam , N-desmethylclobazam , and of concomitant antiepileptic drugs were monitored and prospect ively collected . The effect of clobazam treatment on the apparent clearance steady state of the other antiepileptic drugs was determined by statistical comparison of the clearances of each drug before and after initiation of clobazam treatment using Wilcoxon 's signed rank test . The effects of dosage , age , and concomitant antiepileptic therapy on the levels of clobazam and N-desmethylclobazam was assessed by multivariate analysis . Response to treatment and incidence of adverse effects were evaluated for each conventional antiepileptic drug to possibly identify favorable or unfavorable combinations with clobazam . Whereas the clearances of most conventional antiepileptics are not affected by cotherapy with clobazam , the apparent clearances of valproic acid and primidone are significantly reduced in the presence of clobazam .  Serum concentrations of clobazam  increased with dosage and age , and decreased with phenobarbital cotherapy . Serum concentrations of N-desmethylclobazam significantly correlated with  clobazam serum levels , age , or  clobazam dosage and were significantly increased by cotherapy with phenytoin or carbamazepine . None of the concomitantly used drugs were associated with increased or decreased rate of seizure control .  Twelve patients experienced mild adverse drug effects that were not associated with particular cotherapy , clobazam dose , or plasma concentrations . When clobazam is added to a therapy regimen that includes valproic acid , the patient should be closely followed for possible adverse drug reactions caused by elevated valproic acid serum concentrations , and monitoring of valproate serum levels should be considered . When clobazam doses are gradually increased to achieve an optimal clinical effect , the interactions with phenobarbital , carbamazepine , and phenytoin do not necessitate therapeutic drug monitoring of clobazam or N-desmethylclobazam , because there is a large therapeutic window and a poor correlation between plasma concentrations and therapeutic efficacy . ( J Child Neurol 1997 ; 12:208 - 213 ) 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 PURPOSE This r and omized , double-blind , dose-ranging study evaluated safety and efficacy of clobazam ( CLB ) as adjunctive therapy for drop seizures in patients with Lennox-Gastaut syndrome ( LGS ) . METHODS Sixty-eight patients with LGS aged 2 - 26 years were administered CLB ( low dose = target 0.25 mg/kg/day ; high dose = target 1.0 mg/kg/day ) . The study consisted of 4-week baseline , 3-week titration , and 4-week maintenance periods , followed by a 3-week taper or continuation in an open-label study . Seizure frequency was recorded in a diary by the parent/caregiver throughout the study . RESULTS Weekly drop seizure rates were significantly reduced from baseline in both the high-dose and low-dose groups ; the reduction was significantly greater in the high-dose group . A significantly greater proportion of patients in the high-dose group experienced reductions in drop seizures of > or=25 % , > or=50 % , and > or=75 % compared to the low-dose group ; more patients in the high-dose group experienced a 100 % reduction , but the difference was not significant . Nondrop seizures were also reduced in a dose-dependent manner . In both investigator and parent/caregiver global evaluations , patients in the high-dose group showed significantly greater improvements in overall symptoms compared to low-dose CLB . Adverse events were generally mild or moderate , and were similar between dose groups . Five serious adverse events were reported in four patients , but in no case was CLB discontinued . CONCLUSIONS Clobazam was well tolerated and reduced drop seizure rates ; high-dose CLB was more effective than low-dose CLB . Other seizure types were also reduced Remission of seizures is a crucial measure of outcome in epilepsy . The National General Practice Study of Epilepsy ( NGPSE ) aim ed to investigate the remission of  patients with epilepsy  and the effect of various factors on the likelihood of remission . The NGPSE is a prospect i ve population -based study free from major selection bias . We enrolled 1091 patients with newly diagnosed or suspected epilepsy who attended one of 275 general practice s throughout the UK between 1984 and 1987 .  Remission was analysed in those patients who were classified after 6 months as having definite epilepsy ( n = 564 ) or possible epilepsy ( n = 228 ) . After 9 years from the index seizure , 86 % ( 95 % CI 81 - 90 ) of patients with definite epilepsy had achieved a remission of 3 years and 68 % ( 61 - 75 ) a remission of 5 years . For the complete cohort , including those with possible epilepsy , the remission rates at 9 years were 87 % ( 83 - 91 ) for 3-year remission and 71 % ( 65 - 77 ) for 5-year remission . The proportion of patients with definite epilepsy who were still in remission at 9 years ' follow-up ( terminal remission ) was 68 % ( 62 - 74 ) for 3-year and 54 % ( 48 - 60 ) for 5-year remission . 61 % ( 56 - 68 ) of patients with idiopathic seizures and 61 % ( 46 - 75 ) of those with remote symptomatic epilepsy had achieved 5-year remission by 9 years . Overall , age and seizure type had little effect on the chances of achieving remission . This study confirms the good outcome for seizure control in the majority of patients 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 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 BACKGROUND More than 30 percent of patients with epilepsy have inadequate control of seizures with drug therapy , but why this happens and whether it can be predicted are unknown . We studied the response to antiepileptic drugs in patients with newly diagnosed epilepsy to identify factors associated with subsequent poor control of seizures . METHODS We prospect ively studied 525 patients ( age , 9 to 93 years ) who were given a diagnosis , treated , and followed up at a single center between 1984 and 1997 . Epilepsy was classified as idiopathic ( with a presumed genetic basis ) , symptomatic ( result ing from a structural abnormality ) , or cryptogenic ( result ing from an unknown underlying cause ) . Patients were considered to be seizure-free if they had not had any seizures for at least one year . RESULTS Among the 525 patients , 333 ( 63 percent ) remained seizure-free during antiepileptic-drug treatment or after treatment was stopped . The prevalence of persistent seizures was higher in patients with symptomatic or cryptogenic epilepsy than in those with idiopathic epilepsy ( 40 percent vs. 26 percent , P=0.004 ) and in patients who had had more than 20 seizures before starting treatment than in those who had had fewer ( 51 percent vs. 29 percent , P<0.001 ) . The seizure-free rate was similar in patients who were treated with a single established drug ( 67 percent ) and patients who were treated with a single new drug ( 69 percent ) . Among 470 previously untreated patients , 222 ( 47 percent ) became seizure-free during treatment with their first antiepileptic drug and 67 ( 14 percent ) became seizure-free during treatment with a second or third drug . In 12 patients ( 3 percent ) epilepsy was controlled by treatment with two drugs . Among patients who had no response to the first drug , the percentage who subsequently became seizure-free was smaller ( 11 percent ) when treatment failure was due to lack of efficacy than when it was due to intolerable side effects ( 41 percent ) or an idiosyncratic reaction ( 55 percent ) . CONCLUSIONS Patients who have many seizures before therapy or who have an inadequate response to initial treatment with antiepileptic drugs are likely to have refractory epilepsy Case 1-This patient was investigated at the age of 18 for recurrent urinary infection .  She had been aware of symptoms only for the preceding few months . The following year intravenous urography showed a normal right kidney and a shrunken left kidney with clubbing of the calyces ( fig ( a ) ) consistent with chronic pyelonephritis . On micturating cystography there was reflux up the left ureter as far as the renal pelvis but without dilatation of the renal tract . Cystoscopy showed a localised trigonitis . She was treated initially by urethral dilatation but , after a further recurrence of infection with haematuria , she underwent left nephrectomy at the age of 19 . Histological examination confirmed the presence of severe chronic pyelonephritis . She continued to suffer from urinary infection and haematuria in the year after nephrectomy , at which point she was lost to follow up . Case 2 is the twin sister of case 1 . They were always regarded as identical , and identity was confirmed in 19 red cell types and the four HLA-A and HLA-B types ( courtesy of Dr Ann Collins ) . She presented to one of us in general practice with a history of recurrent urinary infection , in which the first proved attack was at the age of 24 . In view of the family history she was referred for investigation ; no evidence of chronic pyelonephritis was seen on intravenous urogram ( fig ( b ) 
    Output:
    
Clobazam as an add-on treatment may reduce seizure frequency and may be most effective in partial onset seizures .
However , it is not clear who will best benefit and over what time-frame .