Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial. Incidence of Anticonvulsant Osteomalacia and Effect of Vitamin D: Controlled Therapeutic Trial Enhancing antiepileptic drug adherence: A randomized controlled trial In utero antiepileptic drug exposure Efficacy and tolerability of calcium, vitamin D and a plant-based omega-3 oil for osteopenia: a pilot RCT. High Doses of Vitamin D to Reduce Exacerbations in Chronic Obstructive Pulmonary Disease 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 Quantifying the response to antiepileptic drugs A randomized double-blind placebo-controlled add-on trial of lamotrigine in patients with severe epilepsy Assessment of CNS effects of antiepileptic drugs by using quantitative EEG measures. Vitamin D supplementation improves neuromuscular function in older people who fall. Therapy of steroid-induced bone loss in adult asthmatics with calcium, vitamin D, and a diphosphonate. Low-Dose Vitamin D Prevents Muscular Atrophy and Reduces Falls and Hip Fractures in Women after Stroke: A Randomized Controlled Trial 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. A double-blind placebo-controlled study of vitamin E treatment of tardive dyskinesia. Seizure Severity and the Quality of Life
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 The bone mineral content ( B.M.C. ) in both forearms ( related to total body calcium ) was measured by photon absorptiometry for a controlled therapeutic trial in a representative sample of epileptic out patients , comprising 226 patients treated with one or two major anticonvulsant drugs ( phenytoin , phenobarbitone , primidone ) .  Initially the mean B.M.C. value for all epileptic patients was 87 % of normal . During treatment with 2,000 international units of vitamin D2 daily for three months an average B.M.C. increase of 4 % was found , whereas the B.M.C. values remained unchanged in the placebo group and in the control groups . The incidence of hypocalcaemia and raised serum alkaline phosphatase was 12 % and 43 % respectively . The biochemical indices of osteomalacia were related to B.M.C. These results indicate that epileptic patients should be closely supervised for the occurrence of anticonvulsant osteomalacia , and , possibly , receive prophylactic treatment with vitamin 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 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 OBJECTIVES Our pilot study tested the efficacy , acceptability and tolerability of DHA supplementation in addition to calcium and vitamin D in individuals with osteopenia . STUDY DESIGN 40 participants were r and omised to either algal oil containing 400 mg docosahexanoic acid ( DHA ) daily or placebo . All participants received 1200 mg calcium carbonate with vitamin D(3 ) 1000 IU daily . MAIN OUTCOME MEASURES Bone mineral density ( BMD ) was measured at baseline and 12 months . Bone turnover was assessed with serum c-terminal telopeptides ( CTx ) at baseline and 12 months . Tolerability and acceptability were assessed using a vali date d question naire . RESULTS Mean CTx was suppressed after 12 months for all participants ( p=0.04 ) with no difference in effect size between DHA and control groups ( p=0.53 ) . Changes in CTx at 12 months were significantly correlated with changes in BMD at the lumbar spine ( p=0.01 ) and total proximal femur ( TPF ) ( p=0.03 ) . There was a non-significant trend towards rising BMD at 12 months . Participants rated the supplements as tolerable and acceptable , with few adverse events . CONCLUSIONS The combination of oral calcium , vitamin D(3 ) and DHA was safe , tolerable and acceptable when used for 12 months by osteopenic individuals in this pilot study . The combination had a positive effect on bone health as indicated by serum CTx , with no effect demonstrated from the addition of DHA 400 mg . Changes in BMD at the lumbar spine and TPF were significantly correlated with changes in CTx , which may be useful in monitoring bone health and response to treatment BACKGROUND Low serum 25-hydroxyvitamin D ( 25-[OH]D ) levels have been associated with lower FEV(1 ) , impaired immunologic control , and increased airway inflammation . Because many patients with chronic obstructive pulmonary disease ( COPD ) have vitamin D deficiency , effects of vitamin D supplementation may extend beyond preventing osteoporosis . OBJECTIVE To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations . DESIGN R and omized , single-center , double-blind , placebo-controlled trial . ( Clinical Trials.gov registration number : NCT00666367 ) SETTING University Hospitals Leuven , Leuven , Belgium . PATIENTS 182 patients with moderate to very severe COPD and a history of recent exacerbations . INTERVENTION 100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year . MEASUREMENTS The primary outcome was time to first exacerbation . Secondary outcomes were exacerbation rate , time to first hospitalization , time to second exacerbation , FEV(1 ) , quality of life , and death . RESULTS Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group ( mean between-group difference , 30 ng/mL [ 95 % CI , 27 to 33 ng/mL ] ; P < 0.001 ) . The median time to first exacerbation did not significantly differ between the groups ( hazard ratio , 1.1 [ CI , 0.82 to 1.56 ] ; P = 0.41 ) , nor did exacerbation rates , FEV(1 ) , hospitalization , quality of life , and death . However , a post hoc analysis in 30 participants with severe vitamin D deficiency ( serum 25-[OH]D levels < 10 ng/mL ) at baseline showed a significant reduction in exacerbations in the vitamin D group ( rate ratio , 0.57 [ CI , 0.33 to 0.98 ] ; P = 0.042 ) . LIMITATION This was a single-center study with a small sample size . CONCLUSION High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations . In participants with severe vitamin D deficiency at baseline , supplementation may reduce exacerbations . PRIMARY FUNDING SOURCE Applied Biomedical Research Program , Agency for Innovation by Science and Technology ( IWT-TBM ) 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 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 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 PURPOSE Antiepileptic drugs ( AEDs ) can be associated with adverse neurologic effects including cognitive dysfunction . Objective methods for recognizing AED effects on the brain could be valuable for long-term management . We compared quantitative EEG measures and cognitive tests in a group of patients beginning or ending AED therapy .  METHODS Subjects included 20 patients beginning AED therapy ( AEDon ) , 12 patients stopping AED therapy ( AEDoff ) , 33 patient controls receiving stable AED therapy ( AEDco ) , and 73 healthy controls ( Nco ) . All subjects underwent structured EEG recording and a cognitive test battery before change in AED dose and again 12 - 16 weeks later , > or=4 weeks after the last dose change . Four occipital EEG measures ( peak frequency , median frequency , relative theta and delta power ) were analyzed . Cognitive test changes were scored by using test-retest regression equations based on the Nco subjects . Wilcoxon tests were used for two-group comparisons . RESULTS AEDons had a significant decrease , and AEDoffs , a significant increase in the peak frequency of the EEG rhythm , as compared with controls . Results for median frequency and theta power were similar . Change in the EEG peak frequency correlated with an aggregate cognitive change measure ( r2= 0.71 ; p < 0.001 ) , individual cognitive measures , and subjective complaints . Of the combined AEDon/AEDoff patients , 58 % exceeded the 95 % confidence interval for test-retest change in EEG peak frequency . CONCLUSIONS Quantitative measures derived from the occipital EEG are sensitive to AEDs and correlate with AED-related cognitive effects and subjective complaints . Although this correlation does not indicate a direct relation , quantified EEG may be a practical measure of AED impact on the brain BACKGROUND vitamin D supplementation reduces the incidence of fractures in older adults . This may be partly mediated by effects of vitamin D on neuromuscular function . OBJECTIVE to determine the effects of vitamin D supplementation on aspects of neuromuscular function known to be risk factors for falls and fractures . DESIGN r and omised , double-blind , placebo-controlled study . SETTING falls clinic taking referrals from general practitioners and accident and emergency department . SUBJECTS 139 ambulatory subjects ( > /=65 years ) with a history of falls and 25-hydroxyvitamin D ( 25OHD ) < /=12 microg/l . INTERVENTION patients were r and omised to receive a single intramuscular injection of 600,000 i.u . ergocalciferol or placebo . OUTCOME MEASURES assessment s including biochemistry , postural sway , choice reaction time ( CRT ) , aggregate functional performance time ( AFPT ) , and quadriceps strength were carried out at baseline and 6 months post-intervention . RESULTS baseline characteristics were comparable between both groups . 25OHD in the treatment group increased significantly at 6 months . AFPT deteriorated in the control group and improved in the intervention group , representing a significant difference between groups ( + 6.6 s versus -2.0 s , t = 2.80 , P < 0.05 ) . Similar changes were observed for CRT ( -0.06 s versus + 0.41 s , t = -2.52 , P < 0.01 ) and postural sway ( + 0.0025 versus -0.0138 , t = 2.35 , P < 0.02 ) . There was no significant difference in muscle strength change between groups ( -10 N versus -2 N , t = -1.26 , ns ) . A significant correlation between change in AFPT and change in 25OHD levels was observed ( r = 0.19 , P = 0.03 ) . There was no significant difference in the number of falls ( 0.39 versus 0.24 , t = 1.08 , P = 0.28 ) or fallers ( 14 versus 11 , P = 0.52 ) between two groups . CONCLUSIONS vitamin D supplementation , in fallers with vitamin D insufficiency , has a significant beneficial effect on functional performance , reaction time and balance , but not muscle strength . This suggests that vitamin D supplementation improves neuromuscular or neuroprotective function , which may in part explain the mechanism whereby vitamin D reduces falls and fractures In a prospect i ve , controlled , and r and omized clinical trial , we examined the effects of treatment with vitamin D ( 1,000 IU/d ) , calcium ( 1 g/d ) , and ethane-1-hydroxy-1,1-diphosphonate ( EHDP ; 7.5 mg/kg body weight ) on vertebral bone mass in fourteen asthmatics undergoing long-term treatment with systemically applied corticosteroids .  The extent of steroid-induced bone loss was judged by vertebral bone density of the lumbar spine measured by dual-photon absorptiometry as well as by vertebral crush fracture incidence examined by conventional X-ray . Results of the measurements before treatment and after six mo were compared with those of an untreated control group of nineteen asthmatics .  Bone density increased during the observation period by 5 % in the treated group , compared with a decrease of 4.3 % in the untreated control group ( p < 0.01 ) . Moreover , in the treated group no radiologically visible new fractures occurred ; in the control group new fractures were observed in four patients . There were no serious side effects of the applied drugs during the 6-mo period . Therefore , the combination of EHDP , calcium , and vitamin D appears to be a useful regimen for the management of steroid-induced bone loss in adult asthmatics OBJECTIVE Vitamin D supplementation is suggested to reduce the risk of falls among ambulatory or institutionalized elderly subjects . The present study was undertaken to address the reduced risk of falls and hip fractures in patients with long-st and ing stroke by vitamin D supplementation . METHODS Ninety-six elderly women with poststroke hemiplegia were followed for two years . Patients were r and omly assigned to one of the two groups , and 48 patients received 1,000 IU ergocalciferol daily , and the remaining 48 received placebo . The number of falls per person and incidence of hip fractures were compared between the two groups . Strength and tissue ATPase of skeletal muscles on the nonparetic side were assessed before and after the study . RESULTS At baseline , serum 25-hydroxyvitamin D levels were in the deficient range ( < 10 ng/ml ) in all patients ; and vitamin D treatment enhanced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels .  Vitamin D treatment accounted for a 59 % reduction in falls ( 95 % CI , 28 - 81 % ; p = 0.003 ) . There were increases in the relative number and size of type II muscle fibers and improved muscle strength in the vitamin D-treated group . Hip fractures occurred in 4 of 48 placebo group and 0 in 48 vitamin D2 group during the 2-year study period ( log-rank , p = 0.049 ) . CONCLUSION Vitamin D may increase muscle strength by improving atrophy of type II muscle fibers , which may lead to decreased falls and hip fractures 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 BACKGROUND This study was design ed to determine if vitamin E is effective in reducing the severity of abnormal movements in patients with tardive dyskinesia ( TD ) . METHOD Thirty-five patients completed a double-blind placebo-controlled parallel-group study of vitamin E. Seventeen of the patients were r and omly assigned to receive 800 IU b.i.d . of vitamin E and 18 were assigned to placebo for 2 months . Twenty-nine patients had a diagnosis of schizophrenia and 6 of mood disorder . Patients were assessed using modified versions of the Abnormal Involuntary Movement Scale ( m AIMS ) , Simpson-Angus Scale for extrapyramidal side effects , and Brief Psychiatric Rating Scale . Additionally , a subgroup of 23 patients were assessed using instrumental measurements of dyskinesia . RESULTS There was a significant reduction of dyskinesia in the vitamin E group , but not the placebo group , on both the m AIMS and the instrumental assessment s. The overall reduction in m AIMS in the active group was 24 % , with 5 ( 29 % ) of 17 patients demonstrating greater than 33 % reduction in score . There was a greater reduction in mean m AIMS score ( 35 % ) with vitamin E in the subgroup of patients with TD for 5 years or less compared with the reduction ( 11 % ) in patients with TD for greater than 5 years . No change was observed in parkinsonism . In the patients with schizophrenia , there was a reduction in positive symptoms after vitamin E. CONCLUSION Vitamin E appears to be effective in reducing the severity of TD , especially in patients who have had TD for 5 years or less 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
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 .