***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: Epilepsy arises from an imbalance of inhibitory and excitatory influences in the brain . Vigabatrin ( VIG ) decreases the breakdown of the inhibitory neurotransmitter gamma-aminobutyric acid , whereas lamotrigine ( LTG ) reduces presynaptic excitatory amino acid release . 22 patients with refractory epilepsy , treated with an anticonvulsant regimen containing VIG , entered a balanced , double blind , placebo controlled , crossover trial of additional LTG . Treatment periods of 12 weeks ( 25 mg , 50 mg , 100 mg LTG twice daily for four weeks at each dose , and matched placebo ) were followed by wash out intervals of four weeks . 14 of the 20 patients completing the study improved , result ing in a significant fall in seizure days and numbers . Analysis of seizure type confirmed a beneficial effect on partial and secondary generalised tonic-clonic seizures . At the highest LTG dose ( 200 mg daily ) there was a median fall of 37 % in seizure count with nine ( 45 % ) patients reporting > 50 % reduction . Three of these patients were seizure free during this month of treatment . Side effects were minimal throughout the study . Concentrations of other antiepileptic drugs , including those of carbamazepine 10,11-epoxide , were not modified by LTG . This study suggests a substantial efficacy for a regimen containing VIG and LTG . Combinations of drugs with complementary modes of action may provide a rational pharmacological approach to the management of refractory epilepsy The efficacy of lamotrigine ( LTG ) , a new antiepileptic drug ( AED ) chemically unrelated to drugs in current use , was evaluated in 21 in- patients ( 18 males , 3 females ; mean age 34.6 ; range 23 - 42 years ) with severe refractory epilepsy . An add-on double-blind placebo-controlled crossover design was used , with 12 week treatment periods , and a 6 week washout period . Subjects were allocated to 1 of 2 dosing schedules according to their concomitant AEDs . Doses were increased according to clinical response . Although there was no significant reduction in total seizure count during the lamotrigine treatment period compared to placebo , there appears to be a drug effect as there was a marked reduction in generalized tonic-clonic seizures in favour of lamotrigine in the last 4 weeks of the treatment period . There was no significant difference in volunteered adverse experiences during active and placebo treatment . Concomitant serum AED concentrations , biochemical and haematological parameters were unaffected by lamotrigine treatment A double-blind , placebo-controlled trial is reported of lamotrigine as add-on treatment in therapy-resistant epilepsy . A within- patients serial design was used , with two 3-month treatment periods and an intervening 6-week washout/crossover period . An unblinded investigator adjusted lamotrigine dosage to achieve a plasma concentration within a previously predicted therapeutic range . All patients had therapy-resistant partial seizures , some in combination with other seizure types and were without serious neurological or intellectual deficit . Of 34 patients recruited only one was withdrawn because of an adverse experience (  maculo-papular rash ) probably related to the experimental drug and 30 completed the trial . The other 3 withdrawals were due to default during baseline , dispensing error and cholecystectomy . There was a modest statistically significant reduction in total and partial seizures on lamotrigine compared to placebo treatment . There was no difference in adverse experiences or abnormal biochemical or haematological findings between the lamotrigine and placebo periods . The plasma concentrations of concomitantly administered antiepileptic drugs were not affected by lamotrigine treatment . It is concluded that lamotrigine shows promise as an antiepileptic drug with low toxicity The antiepileptic effect of lamotrigine ( Lamictal ® ) was assessed in a double‐blind , placebo‐controlled , crossover trial in 56 adult patients with refractory partial seizures .  Lamotrigine or placebo was added to the patients ' existing antiepileptic drugs ( AEDs ) . The dose of lamotrigine varied from 75 to 400 mg daily . Thirty‐eight patients completed the trial and 7 withdrew because of adverse experiences . There was a statistically significant reduction in seizure counts  on lamotrigine compared with placebo for total seizures ( 30.3 % reduction , 95 % CI 8.4 % , 47.0 % ) , complex partial seizures ( 29.2.% reduction , 95 % CI 3.8 % , 47.9 % ) and secondary generalised seizures ( 37.9 % , CI 18.9 % , 52.4 % ) . The analysis of total seizure days showed a similar significant reduction during lamotrigine treatment for the same seizure categories . There was no statistically significant difference in reporting of adverse events between lamotrigine and placebo except for dizziness which was reported more frequently on lamotrigine than on placebo . There were no differences in abnormal haematological or biochemical findings  between lamotrigine and placebo , and lamotrigine had no effect on plasma concentrations of concomitant AEDs 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 A double-blind , placebo controlled cross over study assessed the efficacy of lamotrigine as adjunct therapy for patients with refractory partial seizures . In addition to the main study , a neuropsychological component evaluated three main areas of cognitive function . These included : i ) Concentration and attention ; ii ) General Cerebral Efficiency , and iii ) Mnestic functions -- immediate , short term and new learning ability .  Ten subjects ( 4 males , 6 females , age range 22 to 53 , mean age 31.3 years ) were involved in the study , each assessed 3 times -- baseline , end of phase I and end of phase II . Whilst statistical analysis proved impracticable due to differing scores across cells , between the results of lamotrigine and placebo , clinical ly , there appeared to be a marginal reduction in General Cerebral Efficiency during the lamotrigine phase . In the light of these tests , the conclusion is advanced that lamotrigine does not specifically impair cognitive function , and that it does not impair mnestic function . An alternate hypothesis of interaction effects is posited for the slight reduction in speed of information processing Efficacy and safety of lamotrigine ( LTG ) as add-on therapy was assessed in a r and omised double-blind placebo-controlled trial of this drug in 23 adult patients with refractory partial seizures . Fifteen patients showed an improvement on  LTG  treatment , with a greater than 50 % decrease in total seizure count in 7 patients . Fourteen patients experienced fewer simple and complex partial seizures , with 8 patients benefitting by more than a 50 % decrease in seizure frequency . The drug was well tolerated over the 2 month treatment period . The plasma concentration of concomitant antiepileptic drugs remained unchanged . No haematological or chemical abnormalities were noted The results of a multicentre , r and omised , double-blind , placebo controlled , crossover trial of lamotrigine as add-on therapy in patients with partial seizures poorly controlled by established antiepileptic drugs ( AEDs ) are presented . The study consisted of two 12 week treatment periods each followed by a four week washout period . During the lamotrigine treatment phase , patients received 150 mg or 300 mg daily dose depending on their concomitant AEDs to achieve concentrations in the range 1 - 3 mg/L. Forty one patients were entered at four centres and all patients entered completed the study . There was a highly significant ( p < 0.001 ) decrease in total seizure counts on lamotrigine compared with placebo . Overall , 22 % of patients experienced at least a 50 % reduction in the total numbers of all seizures types on lamotrigine , compared with none on placebo . When the total numbers of partial seizures ( simple and complex partial ) were analysed there was also a significant ( p < 0.05 ) reduction in seizure counts on lamotrigine compared with placebo . When total numbers of secondarily generalised seizures were compared the trend for a reduction in this seizure type did not achieve significance ( 0.05 < p < 0.1 ) . Concomitant AED plasma concentrations were virtually unchanged . It is concluded that lamotrigine is an effective AED in the treatment of therapy-resistant partial seizures Summary : The need for new antiepileptic drugs ( AEDs ) and more sensitive methods of assessing their efficacy is well recognized . This study was design ed to evaluate the efficacy and safety of lamotrigine ( LTG ) , a potential new AED and to develop and test new outcome measures . A health‐related quality of life ( HRQL ) model was developed which contains previously vali date d measures of anxiety , depression , happiness , overall mood , self‐esteem , and mastery and a specifically design ed seizure severity scale with patient‐ and caregiver‐based components . This HRQL model was used in a r and omized , placebo‐controlled , double‐blind , cross‐over study of LTG in 81 patients with refractory partial seizures .  Seizure frequency was the primary measure and seizure severity and the HRQL were secondary measures of efficacy . The reduction in seizure frequency  with LTG , relative to placebo , was 29.7 % [ 95 % confidence interval ( CI ) 17.8 % , 39.9 % ] for total seizure count , 33.4 % ( 95 % CI 14.8 % , 47.9 % ) for complex partial seizures ( CPS ) and 20.3 % ( 95 % CI 0.3 % , 36.2 % ) for secondarily generalized tonic‐clonic seizures ( GTCS ) . However , although 41 patients elected to continue with LTG , only 11 experienced at least 50 % reduction in total seizures , indicating that other factors influenced their decision . The score with LTG , relative to placebo , was significantly lower for the ictal ( p = 0.017 ) and caregivers ( p = 0.035 ) subscales of the seizure severity scale and significantly higher for happiness ( p = 0.003 ) and mastery ( p = 0.003 ) . Simple correlation and multiple‐regression analyses indicate that the effects on seizure frequency , seizure severity , and psychological variables appear to be independent of each other . This study indicates that LTG is effective in reducing seizure frequency and has additional favorable effects on seizure severity , mood , and perceived internal control . Some of the scales used indicate the potential of secondary measures of efficacy to enhance the sensitivity of trials of new AEDs Summary : The efficacy and safety of lamotrigine ( LTG ) , a new antiepileptic drug ( AED ) , were evaluated in a multicenter , r and omized , double‐blind , placebo‐controlled , cross‐over study of 98 patients with refractory partial seizures . Each treatment period lasted 14 weeks . Most patients were titrated to a LTG maintenance dose of 400  mglday . Seizure frequency  with LTG decreased by ≥50 % , as compared with placebo , in one fifth of patients . Overall median seizure frequency decreased by 25 % with LTG as compared with placebo ( p < 0.001 ) . With LTG  , the number of seizure days decreased by 18 % as compared with placebo ( p < 0.01 ) , and investigator global evaluation of overall patient clinical status  favored LTG by 2 : 1 ( p = 0.013 ) 
    Output:
    
REVIEW ER 'S CONCLUSIONS Lamotrigine add-on therapy is effective in reducing the seizure frequency , in patients with drug-resistant partial epilepsy .