Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. AntiEpileptic drug Monitoring in PREgnancy (EMPiRE): a double-blind randomised trial on effectiveness and acceptability of monitoring strategies. Systematic screening allows reduction of adverse antiepileptic drug effects Early predisposition to osteomalacia in Indian adults on phenytoin or valproate monotherapy and effective prophylaxis by simultaneous supplementation with calcium and 25-hydroxy vitamin D at recommended daily allowance dosage: a prospective study. Quantifying the response to antiepileptic drugs Pregnancy outcome in women exposed to antiepileptic drugs: teratogenic role of maternal epilepsy and its pharmacologic treatment. Assessment of Drowsiness in Epilepsy Patients Receiving Chronic Antiepileptic Drug Therapy Seizure Severity and the Quality of Life Adjustment of treatment increases quality of life in patients with epilepsy: a randomized controlled pragmatic trial. The relationship of depression to antiepileptic drug adherence and quality of life in epilepsy Clinical features associated with placebo response in refractory focal epilepsy Substitution Monotherapy With Levetiracetam vs Older Antiepileptic Drugs: A Randomized Comparative Trial. The effects of oxcarbazepine, levetiracetam, and lamotrigine on semen quality, sexual function, and sex hormones in male adults with epilepsy Effect of anticysticercal treatment on the prognosis of epilepsy in neurocysticercosis: a pilot trial. Seizure reduction and quality of life improvements in people with epilepsy. A randomized double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy In utero antiepileptic drug exposure Influence of concomitant antiepileptic drugs on plasma lamotrigine concentration in adult Japanese epilepsy patients. Early add-on treatment vs alternative monotherapy in patients with partial epilepsy. Felbamate monotherapy has stimulant-like effects in patients with epilepsy Enhancing antiepileptic drug adherence: A randomized controlled trial Early surgical therapy for drug-resistant temporal lobe epilepsy: a randomized trial. Implementation strategies for a Scottish national epilepsy guideline in primary care: results of the Tayside Implementation of Guidelines in Epilepsy Randomized (TIGER) trial.
PURPOSE To evaluate whether use of a bisphosphonate ( risedronate ) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs ( AEDs ) long term can prevent the loss of bone mass ( BMD , bone mineral density ) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures . METHODS Antiepileptic drug and osteoporosis prevention trial ( ADOPT ) was design ed as a prospect i ve 2-year double-blind , r and omized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin , phenobarbital , sodium valproate , or carbamazepine for a minimum of 2 years . All enrolled participants received calcium and vitamin D supplementation , and were r and omized to risedronate or matching placebo .  Total body , bilateral proximal femora , and anteroposterior ( AP ) lumbar spine BMDs in addition to morphometric lateral vertebral assessment s ( LVAs ) were evaluated by a dual energy x-ray absorptiometry ( DXA ) instrument . Comparisons of BMDs were made between baseline , 1 year , and after 2 years of enrollment in the study . The incidence of new vertebral and nonvertebral fractures was secondary end point . KEY FINDINGS Of the 80 patients initially enrolled in the study , 53 patients completed the study . Baseline characteristics of the two groups were similar . At the end of the study , in the placebo plus calcium and vitamin D group , we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69 % ( 18/26 ) of the participants . In the risedronate plus calcium and vitamin D group , we observed significant improvement of BMDs in 70 % ( 19/27 ) of the participants . At the end of the study , the risedronate group experienced a significant increase of BMD at the lumbar spine L1 - 4 ( 1.267 - 1.332 g/cm(2 ) ) , which was significantly larger than that seen in the placebo group ) ( 1.229 g/cm(2 ) vs. 1.245 g/cm(2 ) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora . Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group . SIGNIFICANCE Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69 % of male veterans with epilepsy who were taking AEDs . In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group , which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort BACKGROUND Pregnant women with epilepsy on antiepileptic drugs ( AEDs ) may experience a reduction in serum AED levels . This has the potential to worsen seizure control . OBJECTIVE To determine if , in pregnant women with epilepsy on AEDs , additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels . DESIGN A double-blind , r and omised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken . Stratified block r and omisation with a 1 : 1 allocation method was carried out . SETTING Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK . PARTICIPANTS Pregnant women with epilepsy on one or more of the following AEDs : lamotrigine , carbamazepine , phenytoin or levetiracetam .  Women with a ≥ 25 % decrease in serum AED level from baseline were r and omised to therapeutic drug monitoring or clinical features monitoring strategies . INTERVENTIONS In the therapeutic drug monitoring group , clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control . In the clinical features monitoring group , AED dosage adjustment was based only on clinical features . MAIN OUTCOME MEASURES Primary outcome - seizure deterioration , defined as time to first seizure and to all seizures after r and omisation per woman until 6 weeks post partum . Secondary outcomes - pregnancy complications in mother and offspring , maternal quality of life , seizure rates in cohorts with stable serum AED level , AED dose exposure and adverse events related to AEDs . ANALYSIS Analysis of time to first and to all seizures after r and omisation was performed using a Cox proportional hazards model , and multivariate failure time analysis by the And ersen-Gill model . The effects were reported as hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) . Secondary outcomes were reported as mean differences ( MDs ) or odds ratios . RESULTS A total of 130 women were r and omised to the therapeutic drug monitoring group and 133 to the clinical features monitoring group ; 294 women did not have a reduction in serum AED level . A total of 127 women in the therapeutic drug monitoring group and 130 women in the clinical features monitoring group ( 98 % of complete data ) were included in the primary analysis . There were no significant differences in the time to first seizure ( HR 0.82 , 95 % CI 0.55 to 1.2 ) or timing of all seizures after r and omisation ( HR 1.3 , 95 % CI 0.7 to 2.5 ) between both trial groups . In comparison with the group with stable serum AED levels , there were no significant increases in seizures in the clinical features monitoring ( odds ratio 0.93 , 95 % CI 0.56 to 1.5 ) or therapeutic drug monitoring group ( odds ratio 0.93 , 95 % CI 0.56 to 1.5 ) associated with a reduction in serum AED levels . Maternal and neonatal outcomes were similar in both groups , except for higher cord blood levels of lamotrigine ( MD 0.55 mg/l , 95 % CI 0.11 to 1 mg/l ) or levetiracetam ( MD 7.8 mg/l , 95 % CI 0.86 to 14.8 mg/l ) in the therapeutic drug monitoring group than in the clinical features monitoring group . There were no differences between the groups on daily AED exposure or quality of life . An increase in exposure to lamotrigine , levetiracetam and carbamazepine significantly increased the cord blood levels of the AEDs , but not maternal or fetal complications . Women with epilepsy perceived the need for weighing up their increased vulnerability to seizures during pregnancy against the side effects of AEDs . LIMITATIONS Fewer women than the original target were recruited . CONCLUSION There is no evidence to suggest that regular monitoring of serum AED levels in pregnancy improves seizure control or affects maternal or fetal outcomes . FUTURE WORK RECOMMENDATIONS Further evaluation of the risks of seizure deterioration for various threshold levels of reduction in AEDs and the long-term neurodevelopment of infants born to mothers in both r and omised groups is needed . An individualised prediction model will help to identify those women who need close monitoring in pregnancy . TRIAL REGISTRATION Current Controlled Trials IS RCT N01253916 . FUNDING This project was funded by the National Institute for Health Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol . 22 , No. 23 . See the NIHR Journals Library website for further project information Objective : To determine the effectiveness of systematic screening with a brief 19-item self-report instrument , the Adverse Events Profile ( AEP ) , to reduce adverse effects of antiepileptic drugs ( AEDs ) and improve subjective health status . Methods : The authors performed a prospect i ve r and omized trial comparing the use of the AEP with usual care without the AEP .  Sixty-two patients with an AEP score of ≥45 were enrolled from a consecutive group of 200 consenting adults with epilepsy . Results : The mean percent improvement in AEP scores was greater in the patient group for which clinicians received the AEP compared with the usual care group ( 25 % vs 5 % ; p < 0.01 ) . Mean change in Quality of Life in Epilepsy Inventory (QOLIE)-89 total scores was not different between groups , but for the entire sample QOLIE-89 change was greater for patients having a 15-point improvement in AEP scores than for those with a 0- to 15-point improvement or a worsened score ( 24 vs 12 vs 3 ; analysis of variance , p < 0.008 ) . More patients in the AEP group had a > 15-point improvement in QOLIE-89 score ( p < 0.03 ) . Use of the AEP was associated with a 2.8-fold increase ( 95 % CI , 1.7 to 4.8 ) in AED modifications . No difference in seizure rates was observed . Conclusions : Systematic screening for antiepileptic drug side effects may increase identification of toxicity and guide medication changes to reduce adverse effects and possibly improve subjective health status BACKGROUND Long-term therapy with antiepileptic drugs ( AED ) may be associated with increased total serum alkaline phosphatase ( ALP ) levels and reduced serum calcium , inorganic phosphorous , and vitamin D levels . These adverse biochemical alterations have an adverse effect on bone health . OBJECTIVE To determine ( a ) onset of derangements in serum total ALP and its isoenzymes ( liver , bone ) , calcium and 25-hydroxy vitamin D ( 25-OHD ) concentrations after initiation of treatment with phenytoin or valproic acid monotherapy  and ( b ) the effect of simultaneous supplementation with calcium and 25-OHD at recommended daily allowance ( RDA ) dosage , on these biochemical parameters . MATERIAL S AND METHODS Study was a prospect i ve , case-controlled study in adults . Serum biochemical parameters were estimated at baseline , 30 , 60 , and 90 days of starting AED treatment in the study subjects : Groups -- A ( only calcium supplementation ) and Group B ( both calcium and 25-OHD supplementation ) . STATISTICAL ANALYSIS Mean+/-SD , and students ' paired t test ( between groups A and B ) unpaired students ' t test ( drug-wise ) . RESULTS At 60 days of AED therapy Group A showed a significant increase in serum total ALP ( 78.83+/-11.04 to 101.75 + /- 9.56 IU/l ) ( P < 0.001 ) , ALP-liver isoenzyme , ( 41.97+/- 10.81 to 68.83 + /-7.81 IU/L ) ( P < 0.001 ) , significant decrease in calcium ( 9.30 + /- 0.36 to 8.80 + /- 0.38 mg% ) ( P < 0.001 ) , ALP-bone isoenyzme ( 36.84 + /- 5.01 to 32.92 + /- 6.46 IU/L ) ( P < 0.001 ) , and a significant decrease in 25-OHD ( 25.19 + /- 5.98 to 19.76 + /- 5.35 ng/ml ) ( P < 0.001 ) at 90 days . In contrast Group B , at 60 days , showed a significant decrease in serum total ALP ( 81.92 + /- 19.63 to 54.77 . + /- 11.53 IU/L ) ( P < 0.0001 ) , ALP-liver isoenzyme ( 48.01 . + /- 13.53 to 28.12 . + /- 5.88 IU/L ) ( P < 0.0001 ) , significant increase in calcium ( ( 9.24 + /- 0.31 to 9.93 + /- 0.26 mg% ) ( P < 0.001 ) and ALP-bone isoenzyme levels ( 33.93 + /- 12.2 to 26.25 + /- 8.23 IU/L ) . In Group B , 25-OHD levels showed a significant increase at 90 days ( 24.36 + /- 3.42 to 31.53 + /- 327 ng/ml ) ( P < 0.0001 ) . CONCLUSION Biochemical derangements in calcium metabolism involving the bone are seen by 60 days after starting AED monotherapy , indicating predisposition to development of osteomalacia in these patients . This is preventable by simultaneous oral supplementation with calcium and 25-OHD Objective : To quantify the response to treatment with antiepileptic drugs ( AEDs ) as a function of the past treatment history and identify additional prognostic factors for predicting the response to newly administered AED treatments . Methods : A cohort of 478 consecutive patients who received newly administered AED treatments between January 1999 and December 2004 and were followed prospect ively for 1.5 to 7.5 years in a single epilepsy clinic . Results : The response to newly administered AED treatments was highly dependent on the past treatment history . The seizure-free rates decreased from 61.8 % for the first AED to 41.7 % , 16.6 % , and 0 % after one , two to five , and six to seven past AEDs proved inefficient . This response curve corresponded to a mono-exponential function with a maximal response of 61.8 % and half-decay constant of 1.5 AEDs . Likewise the response curve describing a greater than 50 % reduction in seizure frequency corresponded to a mono-exponential function with a maximal response of 85.3 % and half-decay constant of two AEDs . Three additional independent prognostic factors for predicting the response to AEDs were identified : type of epilepsy , duration of epilepsy , and number of seizures in the 3 months prior to AED initiation . Conclusion : Drug resistance is a grade d process that follows a mono-exponential course with a half-decay constant of 1.5 to two antiepileptic drugs ( AEDs ) . Although relative drug-resistant epilepsy can be diagnosed after failure of two past AEDs , absolute drug resistance requires failure of six AEDs , as a significant minority of patients ( 16.6 % ) is rendered seizure-free by addition of newly administered AEDs even after failure of two to five past antiepileptic drugs . GLOSSARY : AED = antiepileptic drug ; CBZ = carbamazepine ; GBP = gabapentin ; LTG = lamotrigine ; TPM = topiramate ; VA = valproic acid Infants born to epileptic women treated with antiepileptic drugs ( AEDs )  have an increased risk of major congenital malformations ( MCMs ) . In order to determine the role of maternal epilepsy we conducted a prospect i ve cohort study on three cohorts of pregnant women : ( i ) 385 epileptic women treated with AEDs , ( ii ) 310 non-epileptic women treated with AEDs , ( iii ) 867 healthy women not exposed to AEDs ( control group ) . The rate of MCMs in the epileptic group ( 7.7 % ) was not statistically higher than in the non-epileptic one ( 3.9 % ) ( p=0.068 ) . The rate in the first group was higher compared to the control group ( p=0.001 ) , while the rate in the second one was not ( p=0.534 ) . Our data confirm that AEDs therapy is the main cause of the increased risk of malformations in the offspring of epileptic women ; however a teratogenic role of the maternal epilepsy itself can not be excluded Drowsiness is a common complaint among patients with epilepsy taking antiepileptic drugs ( AEDs )  and may be of particular importance because of the potential effects on cognitive abilities . We used a novel EEG‐based measure ( the Awake Maintenance Task , AMT ) to determine objective ly whether patients on chronic , stable AED therapy had impaired ability to maintain wakefulness . Thirty patients receiving AEDs [ carbamazepine ( CBZ ) , phenytoin ( PHT ) , phenobarbital ( PB ) , valproate ( VPA ) ] were compared to 35 healthy controls , 12 seizure patients not taking AEDs , and 16 patients with multiple sclerosis . A structured EEG recording was conducted under controlled conditions , and subjects were tested to determine their ability to maintain wakefulness during a 6‐min unstimulated trial . Testing also included Digit Symbol , auditory reaction time , and subjective measures of fatigue or sleepiness [ Profile of Mood States ( POMS ) , Stanford Sleepiness Scale ( SSS ) ] . Patients receiving AEDs had a mean total drowsiness score of 101 s compared with ≤ 12 s for each of the three control groups ( p < 0.001 ) . One third of the AED‐treated patients had > 120 s of drowsiness , in contrast to only 1 of 63 controls ( p < 0.001 ) . Among patients receiving AEDs , objective EEG drowsiness did not correlate with AED levels or performance measures . Untreated seizure patients had significantly greater complaints of lack of vigor despite a near absence of objective drowsiness on the AMT . These results suggest that epilepsy patients receiving chronic AED therapy have impaired ability to maintain wakefulness . Patient self‐reports of AED‐related sleepiness may not accurately represent this problem Summary : The efficacy of an antiepileptic drug ( AED ) is determined at present by the drug‐elicited reduction in seizure frequency . Reduction of seizure frequency as the sole measure of efficacy does not account for treatment‐induced reductions in seizure severity and positive psychological effects experienced by the patient . A clinical trial was undertaken in which seizure frequency was the primary and seizure severity and psychological well‐being were the secondary measures of efficacy . Psychological assessment and seizure frequency were monitored in patients whose epilepsy was treated with lamotrigine ( LTG ) or placebo .  The results indicate that LTG is an effective AED , causing reductions in seizure frequency and severity and improvements in mood and mastery . In addition , the study demonstrated that the use of seizure severity scales , especially the Ictal subscale , may enhance the sensitivity of assessment of trials of AED treatments BACKGROUND AND PURPOSE Complaints about side-effects of antiepileptic drugs ( AEDs ) may be overlooked in clinical practice . We assessed the value and risks of an active intervention policy for reported complaints in a r and omized controlled pragmatic trial . METHODS This r and omized controlled pragmatic trial included 111 adults treated for epilepsy in seven general hospitals . They were considered well-managed by their treating physician , but reported moderate to severe complaints on a question naire ( SIDAED , assessing SIDe effects in AED treatment ) . The intervention was adjustment of AED treatment ( 53 patients ) , either reduction of dose or switch of AED , versus continuation of treatment unchanged ( 58 control patients ) during 7 months . Primary outcomes were quality of life ( Qolie-10 ) and complaints score . Secondary outcome measures were the occurrence of seizures or adverse events . RESULTS After 7 months , the relative risk ( RR ) for improvement in quality of life was 1.80 ( 1.04 - 3.12 ) for the intervention group compared to control and the RR of decrease in complaints was 1.34 ( 0.88 - 2.05 ) . In 58 % of patients r and omized to adjustment , the medication had indeed been changed . DISCUSSION In conclusion , despite a possible risk of seizure recurrence , adjustment of drug treatment in well-managed patients with epilepsy , who report considerable complaints , improves the quality of life We sought to examine the impact of depression upon antiepileptic drug ( AED ) adherence in patients with epilepsy . We administered the Center for Epidemiologic Studies Depression Scale ( CES-D ) , Neurological Disorders Depression Inventory for Epilepsy ( NDDI-E ) , Seizure Severity Question naire ( SSQ ) , and Quality of Life in Epilepsy-10 ( QOLIE-10 ) and measured AED adherence by utilizing the medication possession ratio ( MPR ) in adult patients with epilepsy identified through a pharmacy cl aims data base . From a sampling frame of over 10,000 patients identified in cl aims , 2750 were r and omly selected and contacted directly by mail to participate in the cross-sectional survey . A total of 465 eligible patients completed a survey . Survey data were combined with administrative cl aims data for analysis . We conducted a path analysis to assess the relationships between depression , adherence , seizure severity , and quality of life ( QOL ) .  Patients with depression scored significantly worse on measures of seizure severity ( p=.003 ) , QOL ( p<.001 ) , and adherence ( p=.001 ) . On path analysis , depression and QOL and seizure severity and QOL were related , but only the NDDI-E scores had a significant relationship with medication adherence ( p=.001 ) . Depression as measured by the NDDI-E was correlated with an increased risk of AED nonadherence . Depression or seizure severity adversely impacted QOL . These results demonstrate yet another important reason to screen for depression in epilepsy For clinical trial design and for clinical practice , it is of importance to assess factors associated with placebo response in patients with refractory epilepsy . We determined factors associated with placebo response in 359 adult patients with refractory focal epilepsy participating in three r and omized placebo-controlled trials of the new antiepileptic drug lacosamide .  At the end of the r and omized 12-week maintenance period , 81 ( 23 % ) of the 359 patients r and omized to placebo achieved at least a 50 % seizure reduction ( responders ) compared to baseline . In contrast , 278 ( 77 % ) patients did not achieve a 50 % seizure reduction ( non-responders ) compared to baseline . In multivariate analysis , five factors , which were present prior to the exposure to placebo , were found to be associated with placebo response . Higher age at study entry improved the chances of placebo response for each year [ p=0.023 , odds ratio ( OR ) 1.034 ( 95 % confidence interval ( 95 % CI ) : 1.005 - 1.063 ) ] . In contrast , a lower chance of placebo response was seen with age at diagnosis of epilepsy of 6 - 20 years compared to ≤5 years [ p=0.041 , OR 0.475 ( 95 % CI : 0.232 - 0.971 ) ] . A history of 7 or more prior lifetime AEDs lowered the chance of achieving placebo response compared to 1 - 3 prior lifetime AEDs [ p<0.001 , OR 0.224 ( 95 % CI : 0.101 - 0.493 ) ] as did a baseline seizure frequency > 10 seizures per 28 days compared to ≤5 seizures per 28 days [ p=0.026 , OR 0.431 ( 95 % CI : 0.205 - 0.904 ) ] . Prior epilepsy surgery lowered the likelihood of placebo response [ p=0.02 , OR 0.22 ( 95 % CI : 0.062 - 0.785 ) ] . We suggest that age at exposure to placebo , age at diagnosis of epilepsy , the number of prior lifetime AEDs , baseline seizure frequency and a history of epilepsy surgery appear to be associated with placebo response in adults with refractory focal epilepsy OBJECTIVE To determine whether patients who fail their first antiepileptic drug ( AED ) have better neuropsychiatric and quality -of-life ( QOL ) outcomes if substituted to levetiracetam monotherapy compared with a second older AED . DESIGN R and omized comparative trial . Participants with partial epilepsy who had failed monotherapy with phenytoin sodium , carbamazepine , or valproate sodium  were r and omized to substitution monotherapy with levetiracetam or a different older AED . Assessment s were performed at baseline , 3 months , and 12 months using question naires measuring neuropsychiatric , QOL , seizure control , AED adverse effects , and neurocognitive outcomes . SETTING Epilepsy service of a teaching hospital . PATIENTS Fifty-one patients were r and omized to levetiracetam and 48 were r and omized to a second older AED ( 25 to valproate and 23 to carbamazepine ) . MAIN OUTCOME MEASURES Proportions showing improvements in depression ( on the Hospital Anxiety and Depression Scale ) and QOL scores ( on the 89-item Quality of Life in Epilepsy Inventory ) at 3 months . RESULTS There were no differences between the groups in depression scores at 3 months ( improvement in 17 of 43 patients [ 39.5 % ] in the levetiracetam group and 15 of 44 patients [ 34.1 % ] in the older AED group ; P = .60 ) , but a greater proportion of the older AED group improved on the 89-item Quality of Life in Epilepsy Inventory compared with the levetiracetam group ( 27 of 38 patients [ 71.1 % ] vs 21 of 43 patients [ 48.8 % ] , respectively ; P = .04 ) . The QOL , anxiety , and AED adverse effects scores were improved in both groups at 3 and 12 months after r and omization . CONCLUSIONS Substitution monotherapy in a patient experiencing ongoing seizures or tolerability issues is associated with sustained improvements in measures of QOL , psychiatric , and adverse events outcomes . Patients switched to levetiracetam do not have better outcomes than those switched to a second older AED . TRIAL REGISTRATION anzctr.org.au Identifier : ACTRN12606000102572 OBJECTIVE To investigate the effects of antiepileptic drugs ( AEDs ; oxcarbazepine [ OXC ] , levetiracetam [ LEV ] , and lamotrigine [ LTG ] ) on semen quality , sexual function , and sex hormones in male adults with epilepsy . METHODS Individual treatment with OXC , LEV , or LTG was r and omly assigned to 38 newly diagnosed male adult patients with epilepsy .  Semen quality and sex hormones were measured before treatment and 6 months after taking the medicine . A question naire was administered using the International Index of Erectile Function Scale-5 and the Premature Ejaculation Diagnostic Tool Self- Assessment Scale to evaluate sexual function , followed by an analysis of the comparison between the treated patients and healthy volunteers ( healthy controls ) as well as the changes and differences between the patients themselves before and after treatment . RESULTS The total sperm count , fast forward movement rate ( FFMR ) , survival rate , and normal sperm rate in the group with epilepsy were lower than those in healthy controls ( P < .05 ) . The FFMR and survival rate of sperm after OXC treatment were significantly higher than before treatment ( P < .05 ) . All semen parameters after LEV and LTG showed a possible trend for improvement , but no significant statistical difference . There was no significant difference in sexual function between patients and the control group , as well as before and after treatment with the 3 different AEDs . There was no significant difference in sex hormone levels in the epilepsy group before treatment compared with the healthy controls , or when compared after treatment with the 3 different AEDs . The marital rate and fertility rate of patients with epilepsy were significantly lower than those of healthy controls ( P < .05 ) . SIGNIFICANCE The semen quality of males with epilepsy is decreased even before treatment . The AEDs ( OXC , LEV , and LTG ) have no significant effect on sexual function and sex hormones , and OXC can improve the sperm FFMR and survival rate Epilepsy secondary to active or inactive neurocysticercosis ( NCC ) is a major public health problem in Latin American countries . In an open-label pilot trial , we evaluated and followed ( mean = 13 months ) 16 patients with epilepsy result ing from active NCC which was treated with anticisticercal ( ACC ) drugs .  These patients were aged 12 - 68 years with confirmed active NCC and seizures not controlled by adequate antiepileptic drug ( AED ) therapy .  Patients were treated with albendazole or praziquantel ( ALB and PZQ , ACC drugs ) and AED monotherapy . The number of NCC cysts was markedly reduced by ACC therapy .  Thirteen patients remained seizure-free and 2 had only one seizure during follow-up . Our data suggest a positive effect of ACC treatment on the prognosis of epilepsy caused by active NCC , but a prospect i ve , double-blind , controlled study with long-term follow-up must be performed to determine whether ACC therapy improves long-term seizure control PURPOSE Previous research suggests that seizure freedom may be necessary to improve health-related quality of life ( HRQOL ) for epilepsy surgery patients , but little is known regarding the seizure-frequency reduction needed to improve HRQOL among medically treated individuals . METHODS With data from 134 adults with refractory complex partial seizures participating in a r and omized controlled antiepileptic drug ( AED ) trial , we compared the change in HRQOL across groups having different levels of change in seizure frequency : 100 % , 75 - 99 % , 50 - 74 % reduction , and 0 - 50 % increase or decrease . Changes over time within each seizure-reduction group also were assessed . HRQOL was measured by the  QOLIE-31 , QOLIE-89 , and SF-36 .  RESULTS Subjects who became seizure free reported significantly more positive change than those who did not on the QOLIE-31 and QOLIE-89 overall scores , the QOLIE-89 mental health , physical health , and epilepsy-targeted composites , as well as the SF-36 mental health summary score . Changes over time in overall QOLIE-31 and QOLIE-89 scores were significantly more positive for subjects who achieved seizure freedom ( i.e. , 100 % reduction in seizure frequency ) than for those who did not . No significant change in QOLIE-31 and QOLIE-89 overall scores was observed for subjects who did not achieve seizure freedom . CONCLUSIONS In this study , HRQOL improvement occurred primarily among patients who achieved complete seizure freedom . Many AED trials use a 50 % seizure-frequency reduction criterion as a trial end point , but measurable impacts of this degree of reduction in seizure frequency on HRQOL in this sample were not observed . These results further support striving for seizure freedom as an epilepsy care goal 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 Background : Pregnancy outcomes following in utero exposure to antiepileptic drugs ( AEDs ) are uncertain , limiting an evidence d-based approach . Objective : To determine if fetal outcomes vary as a function of different in utero AED exposures . Methods : This ongoing prospect i ve observational study across 25 epilepsy centers in the USA and UK enrolled pregnant women with epilepsy from October 1999 to February 2004 to determine if differential long-term cognitive and behavioral neurodevelopmental effects exist across the four most commonly used AEDs . This initial report focuses on the incidence of serious adverse outcomes including major congenital malformations ( which could be attributable to AEDs ) or fetal death .  A total of 333 mother/child pairs were analyzed for monotherapy exposures : carbamazepine ( n = 110 ) , lamotrigine ( n = 98 ) , phenytoin ( n = 56 ) , and valproate ( n = 69 ) . Results : Response frequencies of pregnancies result ing in serious adverse outcomes for each AED were as follows : carbamazepine 8.2 % , lamotrigine 1.0 % , phenytoin 10.7 % , and valproate 20.3 % . Distribution of serious adverse outcomes differed significantly across AEDs and was not explained by factors other than in utero AED exposure . Valproate exhibited a dose-dependent effect . Conclusions : More adverse outcomes were observed in pregnancies with in utero valproate exposure vs the other antiepileptic drugs ( AEDs ) . These results combined with several recent studies provide strong evidence that valproate poses the highest risk to the fetus . For women who fail other AEDs and require valproate , the dose should be limited if possible 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 AIM The aim of this study was to evaluate the impact of two different therapeutic strategies in patients with partial seizures who were intractable to the first prescribed antiepileptic drug ( AED ) ; alternative monotherapy vs early add-on treatment . METHODS We conducted an open , cluster-r and omised , prospect i ve , controlled trial in patients with persistent partial seizures , despite treatment with one AED , who were never administered any other AEDs . Neurologists were r and omised to two strategies : in group A , an alternative monotherapy with a second AED was employed ; in group B , add-on treatment with a second AED was employed . The primary outcome was the percentage of seizure-free patients during a two-month period after six months of treatment . The secondary outcomes were : ( i ) the percentage of patients achieving a 50 % reduction in the number of seizures at six months ; ( ii ) the quality of life based on the Quality Of Life In Epilepsy scale ; and ( iii ) tolerability . RESULTS A total of 143 neurologists were included and r and omised , and 264 patients were evaluated . At six months , the primary outcome was 51 % in group A and 45 % in group B ( p=0.34 ) . The percentage of patients achieving a 50 % reduction in the number of seizures at six months was 76 % in group A and 84 % in group B ( p=0.53 ) . The quality of life and the tolerability did not significantly differ between the two groups . CONCLUSIONS Alternative monotherapy or early treatment initiation with another AED drug result ed in similar efficacy , and the side effects associated with monotherapy and combined therapies were similar , which suggests that individual susceptibility is more important than the number and burden of AEDs used The objective of this study was to assess the psychiatric effects of the antiepileptic drug ( AED ) felbamate ( FBM ) in patients with epilepsy .  FBM is a new AED with a novel putative ( antiglutaminergic ) mechanism . Older AEDs such as carbamazepine and valproate have psychotropic properties , but the psychiatric effects of FBM and other new antiglutamatergic AEDs remain to be determined . Thirty in patients with refractory epilepsy were openly tapered off all AEDs in conjunction with intensive presurgical monitoring prior to a two week r and omized double-blind parallel trial of FBM monotherapy versus placebo , followed by open FBM therapy .  Psychopathology was rated with weekly psychiatric rating scales . Anxiety , depression and seizures increased significantly with AED discontinuation . Acute blind FBM monotherapy yielded antiepileptic and stimulant-like effects ( insomnia , anorexia , and anxiety ) , but failed to influence AED withdrawal-emergent psychopathology . Restarting original AEDs resolved such pathology in FBM drop outs . Chronic open FBM also had stimulant-like effects , with half of the patients displaying psychiatric deterioration and the other half modest improvement compared to baseline therapies . Baseline insomnia and anxiety may be markers for poorer psychiatric responses to chronic open FBM . FBM had stimulant-like effects , lacked anxiolytic effects , and failed to attenuate AED withdrawal-emergent psychopathology . Baseline insomnia or anxiety may predict poorer psychiatric responses to FBM . Further studies are required to assess whether the novel psychiatric effects observed with FBM also occur with other new antiglutamatergic AEDs Suboptimal adherence to antiepileptic drug ( AED ) treatment is commonplace , and increases the risk of status epilepticus and sudden unexplained death in epilepsy . This r and omized controlled trial was design ed to demonstrate whether an implementation intention intervention involving the completion of a simple self-administered question naire linking the intention of taking medication with a particular time , place , and other activity can improve AED treatment schedule adherence . Of the 81 patients with epilepsy who were r and omized , 69 completed a 1-month monitoring period with an objective measure of tablet taking ( electronic registration of pill bottle openings , Medication Event Monitoring System [ MEMS ] ) . Intervention participants showed improved adherence relative to controls on all three outcomes : doses taken in total ( 93.4 % vs. 79.1 % ) , days on which correct dose was taken ( 88.7 % vs. 65.3 % ) , and doses taken on schedule ( 78.8 % vs. 55.3 % ) ( P<0.01 ) . The implementation intention intervention may be an easy-to-administer and effective means of promoting AED adherence CONTEXT Despite reported success , surgery for pharmacoresistant seizures is often seen as a last resort . Patients are typically referred for surgery after 20 years of seizures , often too late to avoid significant disability and premature death . OBJECTIVE We sought to determine whether surgery soon after failure of 2 antiepileptic drug ( AED ) trials is superior to continued medical management in controlling seizures and improving quality of life ( QOL ) . DESIGN , SETTING , AND PARTICIPANTS The Early R and omized Surgical Epilepsy Trial ( ERSET ) is a multicenter , controlled , parallel-group clinical trial performed at 16 US epilepsy surgery centers . The 38 participants ( 18 men and 20 women ; aged ≥12 years ) had mesial temporal lobe epilepsy ( MTLE ) and disabling seizues for no more than 2 consecutive years following adequate trials of 2 br and -name AEDs . Eligibility for anteromesial temporal resection ( AMTR ) was based on a st and ardized presurgical evaluation protocol . Participants were r and omized to continued AED treatment or AMTR 2003 - 2007 , and observed for 2 years . Planned enrollment was 200 , but the trial was halted prematurely due to slow accrual . INTERVENTION Receipt of continued AED treatment ( n = 23 ) or a st and ardized AMTR plus AED treatment ( n = 15 ) . In the medical group , 7 participants underwent AMTR prior to the end of follow-up and 1 participant in the surgical group never received surgery . MAIN OUTCOME MEASURES The primary outcome variable was freedom from disabling seizures during year 2 of follow-up . Secondary outcome variables were health-related QOL ( measured primarily by the 2-year change in the Quality of Life in Epilepsy 89 [ QOLIE-89 ] overall T-score ) , cognitive function , and social adaptation . RESULTS Zero of 23 participants in the medical group and 11 of 15 in the surgical group were seizure free during year 2 of follow-up ( odds ratio = ∞ ; 95 % CI , 11.8 to ∞ ; P < .001 ) . In an intention-to-treat analysis , the mean improvement in QOLIE-89 overall T-score was higher in the surgical group than in the medical group but this difference was not statistically significant ( 12.6 vs 4.0 points ; treatment effect = 8.5 ; 95 % CI , -1.0 to 18.1 ; P = .08 ) . When data obtained after surgery from participants in the medical group were excluded , the effect of surgery on QOL was significant ( 12.8 vs 2.8 points ; treatment effect = 9.9 ; 95 % CI , 2.2 to 17.7 ; P = .01 ) . Memory decline ( assessed using the Rey Auditory Verbal Learning Test ) occurred in 4 participants ( 36 % ) after surgery , consistent with rates seen in the literature ; but the sample was too small to permit definitive conclusions about treatment group differences in cognitive outcomes . Adverse events included a transient neurologic deficit attributed to a magnetic resonance imaging-identified postoperative stroke in a participant who had surgery and 3 cases of status epilepticus in the medical group . CONCLUSIONS Among patients with newly intractable disabling MTLE , resective surgery plus AED treatment result ed in a lower probability of seizures during year 2 of follow-up than continued AED treatment alone . Given the premature termination of the trial , the results should be interpreted with appropriate caution . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00040326 PURPOSE To determine the effectiveness of two dissemination and implementation strategies to implement a national guideline for epilepsy management in primary care setting s. METHODS Three-arm cluster-r and omized controlled trial . The participants were general practitioners from 68 practice s in Tayside , Scotl and , and 1,133 of their patients with self-reported epilepsy treated with antiepileptic medications ( AEDs ) . Practice s were r and omized blind to a control , intermediate , or intensive intervention . CONTROL Postal dissemination of a nationally developed clinical guideline . Intermediate intervention : Postal dissemination of the guideline supported by interactive , accredited workshops , and dedicated , structured protocol documents . Intensive intervention : Intermediate intervention plus a nurse specialist who supported and educated practice s in the establishment of epilepsy review clinics . The primary outcome was the SF-36 health-related quality -of-life instrument . Secondary measures were a battery of prevali date d epilepsy-specific quality -of-life instruments . These were administered at baseline and after the intervention phase . Process of care was assessed by case-note review on number of review meetings and counseling sessions for epilepsy before and after the interventions . RESULTS None of the intervention groups showed any change in the primary or secondary outcome measures or process-of-care measures . CONCLUSIONS None of the intervention strategies led to improvements in patient quality of life or quality of epilepsy care . Further research is needed to discover why the interventions failed , to identify barriers to adoption of guidelines , and to develop strategies that might improve implementation and uptake in the future
All 6 studies that investigated bone mineralization had significant findings ; however , due to varying method ologies , the impact of vitamin D on bone mineralization was inconclusive .
SIGNIFICANCE Vitamin D does appear to have some benefit to bone health in adults with epilepsy , and therefore supplementation could potentially be a requisite to using some AEDs .
OBJECTIVE Several antiepileptic drugs ( AEDs ) have been associated with a detrimental effect on bone health through a reduction in serum vitamin D. Subsequently , several studies have investigated the effect of vitamin D supplementation in persons with epilepsy being treated with AEDs .
The present systematic review of published literature was conducted to determine the effect of vitamin D intervention on bone health in adults with epilepsy .