***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: Older individuals may be more susceptible to cognitive side effects of antiepileptic drugs than are younger adults . This r and omized , double-blind study compared the cognitive effects of lamotrigine ( median maintenance dosage , 500.0 mg/d ) and topiramate ( median maintenance dosage , 300.0 mg/d ) as adjunctive therapy for 16 weeks in patients ≥50 years of age . Fifty-one patients ( lamotrigine , n=25 ; topiramate , n=26 ) were enrolled , and 28 patients ( lamotrigine , n=15 ; topiramate , n=13 ) completed the study . In a combined analysis of all cognitive tests performed , no significant differences between treatment groups were noted . However , analyses of individual cognitive test results revealed that lamotrigine-treated patients had significantly better results on the Controlled Oral Word Association Test and the Symbol-Digit Modalities Test , whereas topiramate-treated patients had significantly more favorable results on the Digit Cancellation Test and the Rey Auditory-Verbal Learning Test . Larger studies are needed to further clarify the differences in the cognitive effects  of lamotrigine and topiramate in older patients Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Lamotrigine ( LTG ) is an antiepileptic drug ( AED ) that was approved in Japan in 2008 . We evaluated the influence of AEDs that induce hepatic enzymes ( including phenytoin ( PHT ) , phenobarbital ( PB ) , carbamazepine ( CBZ ) ) , valproic acid ( VPA ) , and various combinations of these drugs , on plasma LTG concentration in adult Japanese epilepsy patients . A total of 621 patients ( mean age 34.4±11.8 years ) were evaluated retrospectively . We calculated the concentration to dose ratio ( CD ratio ) for LTG  with different AED regimens , and employed multiple regression analysis to determine factors influencing the LTG concentration . There was a linear correlation between the dose and concentration of LTG  in patients treated with LTG ( group I ) , LTG+VPA ( group II ) , LTG+inducers ( group III ) , or LTG+VPA+inducers ( group IV ) . The mean CD ratio of patients on LTG monotherapy was 1.43±0.4 (μg/mL)/(mg/kg ) . When LTG was combined with VPA , the CD ratio increased about 2.2-fold , but there was no significant correlation between the CD ratio and VPA concentration . The mean CD ratios calculated in patients receiving LTG+PHT , LTG+PB , and LTG+CBZ were 0.56 , 0.84 , and 0.91 , respectively . Addition of PHT significantly reduced the CD ratio in a concentration-dependent manner , in comparison with PB and CBZ ( p<0.005 and p<0.001 , respectively ) . Stepwise multiple regression analysis showed that the coefficient of determination of groups I , II , III , and IV were 0.94 , 0.94 , 0.90 , and 0.91 , respectively . In the clinical setting , these findings can help to estimate LTG concentrations and predict the inducing or inhibiting effects of concomitant AEDs PURPOSE To compare controlled-release carbamazepine monotherapy ( CBZ-CR ) with lamotrigine and valproate combination therapy ( LTG + VPA ) in equivalent total drug load , as initial drug regimen in untreated patients with partial and /or generalized tonic-clonic seizures ( GTCS ) . METHODS This unblinded , r and omized , 60-week superiority trial recruited patients having two or more unprovoked seizures with at least one seizure during previous three months . After r and omization into CBZ-CR or LTG + VPA , patients entered into eight-week titration phase ( TP ) , followed by 52-week maintenance phase ( MP ) . Median doses of CBZ-CR and LTG + VPA were 600 mg/day and 75 mg/day + 500 mg/day , respectively . Primary outcome measure was completion rate ( CR ) , a proportion of patients who have completed the 60-week study as planned . Secondary efficacy measures included seizure-free rate ( SFR ) for 52-week of MP and time to first seizure ( TTFS ) during MP . RESULTS Among 207 r and omized patients , 202 underwent outcome analysis ( 104 in CBZ-CR  , 98 in  LTG  + VPA ) . CR was 62.5 % in CBZ-CR and 65.3 % in LTG + VPA ( p = 0.678 ) . SFR during MP was higher in LTG + VPA ( 64.1 % ) than CBZ-CR ( 47.8 % ) ( P = 0.034 ) . TTFS was shorter with CBZ-CR ( p = 0.041 ) . Incidence of adverse effects ( AEs ) were 57.7 % in CBZ-CR and 60.2 % in LTG + VPA and premature drug withdrawal rates due to AEs were 12.5 % and 7.1 % , respectively , which were not significantly different . CONCLUSION CR was comparable between LTG + VPA and CBZ-CR , however , both SFR for 52-week MP and TTFS during MP were in favor of LTG + VPA than CBZ-CR . The study suggested that LTG + VPA can be an option as initial drug regimen for untreated patients with partial seizures and /or GTCS except for women of reproductive age 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 In this retrospective controlled study , the impact of adjunctive lacosamide ( LCM ) on cognition in patients with epilepsy was evaluated and compared with that of topiramate ( TPM ) and lamotrigine ( LTG ) in a naturalistic outpatient setting . Cognition was investigated by means of objective assessment of executive functions ( EpiTrack ® ) and verbal memory and by subjective ratings of self-perceived side effects ( cognition , mood , and vegetative ) . Quality of life was assessed using the QOLIE-10 question naire . Patients underwent assessment at baseline and after a median follow-up interval of 32 weeks . Forty-four patients were treated with LCM , 11 with LTG , and 15 with TPM .  Treatment arms differed with regard to the age at onset of epilepsy ( LTG > TPM ) and to seizure control from baseline to follow-up , which was best in patients whose seizures were treated with LTG ( 55 % vs. 16 % in patients whose seizures were treated with  LCM and 13 % in patients whose seizures were treated with TPM ) . Groups did not differ in the type of epilepsy , daily drug load or drug load change , nor in baseline seizure frequency . Repeated measures statistics controlling for epilepsy onset and seizure outcome showed deteriorated executive functions  with TPM ( F=7.5 , p=0.001 ) . On an individual level ( reliable change indices ) , 53 % of the patients whose seizures were treated with TPM showed losses in this domain ( LCM 14 % , LTG 27 % ) and none of the patients showed improvement ( LCM 23 % , LTG 27 % ; χ(2)=11.8 , p=0.019 ) . No differences in memory , quality of life , or mood were noted among patients in the three treatment arms . Subjective cognitive complaints increased in 5 of the 9 patients whose seizures were treated with TPM ( LCM 1/9 , LTG 0/9 ; χ(2)=11.9 , p=0.025 ) . The findings of this study demonstrate for the first time that the cognitive side effect profile of LCM is comparable to that of LTG and superior to that of TPM . This is indicated by both subjective and objective measures . Given the naturalistic setting and the retrospective nature of the study , a follow-up prospect i ve , r and omized trial with larger sample sizes is required to confirm these findings Efficacy and tolerability of once-daily adjunctive lamotrigine extended-release ( XR ) for primary generalized tonic-clonic ( PGTC ) seizures in epilepsy were evaluated . Patients ( n = 153 ) ≥ 13 years old diagnosed with epilepsy with PGTC seizures were r and omized to once-daily adjunctive lamotrigine XR or placebo in a double-blind , parallel-group trial comprising a baseline phase , a 7-week double-blind escalation phase , and a 12-week double-blind maintenance phase . Lamotrigine XR was more effective than placebo with respect to median percentage reduction from baseline in weekly PGTC seizure frequency ( primary endpoint-19-week treatment phase : 75.4 % vs 32.1 % , P<0.0001 ; escalation phase : 61.9 % vs 30.6 % , P = 0.0016 ; maintenance phase : 89.7 % vs 33.3 % , P<0.0001 ) . Lamotrigine XR was more effective than placebo with respect to the percentage of patients with ≥50 % reduction in PGTC seizure frequency . Significant separation from placebo for ≥50 % reduction in PGTC seizures was observed beginning on treatment day 8 . The most common adverse event was headache ( lamotrigine XR 14 % , placebo 16 % ) The efficacy of lamotrigine ( LTG ) , a new antiepileptic drug ( AED ) chemically unrelated to drugs in current use , was evaluated in 21 in- patients ( 
    Output:
    
The adverse events significantly associated with lamotrigine were : ataxia , dizziness , diplopia ( double vision ) , and nausea .
The limited data available precluded any conclusions about effects on cognition and quality of life .
No important heterogeneity between studies was found for any of the outcomes .
Lamotrigine as an add-on treatment for drug-resistant focal seizures appears to be effective in reducing seizure frequency , and seems to be fairly well-tolerated .