Intervention [5] Comparison [6]

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1 Cowan LD. The epidemiology of the epilepsies in children. Mental Retardation and Developmental Disabilities Res Reviews, 2002; 8: Review article Paediatric patients Discusses incidence and prevalence rates of epilepsy by Age, Sex and Race/ethnicit y. Describes frequencies of s types and epilepsy syndromes in children Tudor-Smith C et al. Phenytoin versus valproate partial onset s and generalized onset tonic clonic Cochrane database of Systematic Reviews Issue 4 Art No CD DOI: / CD Systematic review. Randomized controlled trials in children or adults partial onset generalized onset tonicclonic Trials must have included a comparison of valproate. Data were available 669 individuals from five trials, representing 60% of the recruited into the eleven trials that met the inclusion criteria Of the five trials which individual patient data were provided, one recruited individuals of all ages (Ramsay 1992), one recruited children only (de Silva 1996), two recruited adults only (Heller 1995; Turnbull 1985) and one trial recruited elderly people (Craig 1994). Newly diagnosed people were recruited in all five To review the effects of compared to valproate when used as in people partial onset s (simple/complex partial or out secondarily generalization) or generalized onset tonic-clonic s ( or out other generalized types). Phenytoin compared to valproate when used as Analysis on an intention-totreat basis. Results are expressed as a hazard ratio (HR) and 95% interval, and by convention a HR greater than one indicates that an event is more likely on. Time to Time to drawal of For this outcome, a HR greater than one indicates a valproate. Time to achieve 12 For this External sources of support Medical Research Council UK NHS R&D UK Internal sources of support University of Liverpool UK Walton Discusses epilepsy and development al disabilities, aetiology, specific types of childhood s and prognosis. 1

2 trials. (retention time) was chosen as the primary outcome. Participants achieved this outcome if was drawn poor control, adverse effects, noncompliance or if additional addon was initiated (i.e. had failed). This is a combined outcome reflecting both efficacy and tolerability and is an outcome to which the individual contributes. It is the primary outcome measure recommended by the Commission on Antiepileptic Drugs of the International League Against Epilepsy (Commission 1998). (2) Time to achieve 12 ( free period). outcome, a HR greater than one indicates a. Time to achieve six For this outcome, a HR greater than one indicates a. Time to first post randomizatio n For this outcome, a HR greater than one indicates a valproate. Centre Neurolog y and Neurosur gery UK 2

3 Tudor-Smith C et al Carbamazepine versus epilepsy. Cochrane database of Systematic Reviews 2002, Issue 2 Art No CD DOI: / CD Taylor S et al. Phenobarbitone versus partial onset s and generalized onset tonic-clonic Cochrane Database of Systematic Reviews issue 2 Art No CD DOI:10,1002/ CD Systematic review Systematic review 551 (adults and children) in 3 Trials, available analysis. This is 61% of the in the 9 trials that met the inclusion criteria 599 (adults and children) in 4 trials. This is 65% of the in the 10 studies meeting the inclusion criteria Adults or Children partial onset generalised onset tonic-clonic Adults and children partial onset generalised onset tonic-clonic To review the best evidence comparing and when used as in people partial onset generalised onset tonic-clonic To review the effects of phenobarbitone compared to when used as in patients partial onset generalised tonicclonic s of of phenobarbiton e and (3) Time to achieve six. (4) Time to first post randomization. (5) Quality of life if available. 12 s a)time to b)12 c)6 d) first post randomisation. Results were expressed as hazard ratios plus intervals, where a HR greater than 1 indicates an event is more likely on 12 s A)Time to B)12 C) First postrandomisation. Results were expressed as Hazard ration and 95% interval, where a HR >1 indicates A)Time to HR=0.97 (95% CI ) B)Time to 12 HR=1 (95% CI ) C)Time to (95% CI D)Time to first 0.91 (95% CI ) A)Time to HR= % CI ) B)Time to 12 HR=0.93 (95% CI ) C)Time to first HR=0.84 (95% CI The results suggest no overall difference between carbamazepi ne and these outcomes, but intervals are wide. These results indicated a statistically in terms of drawal (probably related to adverse effects associated 3

4 Muller M et al Oxcarbazepine versus epilepsy. Cochrane Database of Systematic reviews 2006 Issue 2. Art No CD DOI / CD pub2 Systematic Review of randomised controlled trials Data were available 480 patients from 2 trials, representing 100% of the patients recruited into the 2 trials that met the inclusion criteria. Adults and children epilepsy To review the best evidence comparing and when used as in patients epilepsy of in children and adults epilepsy. an event is more likely to occur earlier on phenobarbitone then A)Time on B)Time to achieve 6, 12 and 24 C)Time to first postrandomisation D) Quality of life if available. Results are expressed as Hazard ratios (HR) and 95% intervals, where HR>1 indicates an event is more likely on 1.05) phenobarbito ne), and a non in terms of 12. Results time to first suggest a non phenobarbito ne A)Time to HR=1.64 ( ) B)Time to 6 HR=0.89 ( ) Time to 12 HR=0.92 ( ) C)Time to first HR=1.07 ( ) No either drug patients generalised onset s could be identified. A potentially important in time to drawal oxcarbazepin e patients partial onset s was identified. However, current data do not allow a statement as to whether 4

5 Forsythe I et al. Cognitive improvement in new cases of epilepsy randomly assigned to, and sodium valproate. Developmental Medicine and Child Neurology 1991:33; Randomised, prospective blind study of children to, or sodium valproate compared to controls 64 Children aged 5-14 years of age who had had a) three tonic clonic s, 2) three complex partial 3)three partial s secondary generalisation 31 children referred because of nocturnal enuresis and 9 migraine acted as controls. Effect of, and sodium valproate on cognitive function in newly diagnosed epilepsy. Active group versus control group 12 s Cognitive assessments: 1.Visual recall 2.Auditory recall 3.Visual scanning 4.Strrop test (concentration) 5.Speed of inmation processing 6. Standard scales of intellectual functioning and reading Memory tests: no difference between medications (although impaired recent recall was noted on at 6 s and 1 year. Vigilance: No differences between medications 1.NHS 2. Ciba Geigy PLC Sanofi PLC oxcarbazepin e is equivalent, superior or inferior to in terms of control. Speed of Inmation processing: No difference between the drug groups, although it was impaired y both and. Concentration: no differences between the drug groups 5

6 Thilothammel et al. of phenobarbitone, sodium valproate randomized double blind study. Indian Paediatrics ; de Silva M et al. Randomised comparative trial of phenobarbitone,, or sodium valproate newly diagnosed childhood epilepsy. The Lancet 1996; 347: (Alder Hey Library) Randomised, double-blind trial Randomised, comparative trial of ( phenobarbiton e,,, sodium valproate) in newly diagnosed epilepsy 151 Paediatric outpatients ( 4-12 years of age) generalised tonicclonic convulsions in a tertiary care hospital (India) 167 Children aged 3-16 years of age who had had at least 2 previously untreated tonicclonic or partial s or out secondary generalisation of efficacy and side effects of, phenobarbitone or sodium valproate in controlling generalised tonicclonic Random allocation to one of the 4 antiepileptic drugs Administration of active drug (phenobarbito ne or or sodium valproate) versus placebo Comparative efficacy of the drugs 2 years Recurrence of convulsion and side effects. Median duration 44 s (3-88 s) Clinical, haematological and biochemical parameters were assessed ly. Serum drug levels were assesses periodically Time to first recurrence after the start of therapy. Time to achieve a 1-year from all s (or the last date of summarised by a Kaplan Meier of Standard tests of intelligence and reading. Difference between and at 1 year. The proportion of children recurrence did not differ amongst the 3 groups. More than 1 side effect was observed in 32% of children on Phenobarbiton e; 40% of children on and 19% of children on sodium valproate. This difference was statistically Overall outcome all 4 drugs was good. 20% of children remained free and 73% had achieved a 1- year by 3 years of. Phenytoin was Internation al epidemiolog y network. Boots Pharmaceut icals, Reckitt and Coleman India Ltd. & Rhone Poulenc India Ltd. Medical Research Council. Health promotion trust, Ciba- Geigy, Parke- Davis, Sanofi. Most side effects disappeared on adjustment of dosage. Least expensive, phenobarbito ne may be preferred as the drug of first choice, but only in pre-school children. Sodium valproate is preferred schoolchildre n. 6

7 recurrence free follow-up. Frequency of unacceptable side- effects necessitating drawal more likely to be drawn 9%) than (4%) or sodium valproate (4%) Guerreiro M et al. A double-blind controlled trial of versus in children and adolescents epilepsy. Epilepsy Research 1997; 27(2): Multi-centre, randomised, parallel group trial 3 phases: a retrospective baseline assessment, double-blind and a long term open extension 193 patients enrolled. 153 included in the results Children aged 5-18 years newly diagnosed epilepsy partial generalised tonicclonic Recruitment centres were located in Brazil and Argentina Monotherapy or of efficacy, tolerability and retention in patients receiving or the management of partial generalised tonic- clonic 56 weeks A)efficacy B)Tolerability C)Treatment retention A) Overall 61% and 60% of patients were free during the maintenance period in the and groups respectively. No statistically difference noted. B) Tolerability: 2 recipients and 14 recipients were drawn due to adverse experiences. This was a statistically difference in favour of. The proportion of patients experiencing at least 1 adverse effect was 82.3% and 89.4% Novartis Pharma 7

8 Temkin NR. Antiepileptogenesis and prevention trials antiepileptic drugs: metaanalysis of controlled trials. Epilepsia 2001;42(4): Meta-analysis of controlled trials (47 in total) identified from Medline, Embase and the Cochrane Clinical Trials Register. Seventeen trials included as a single or comparative agent. Between 49 and 404 patients were included in the different studies Adults and children 1.Alcohol related conditions ( versus placebo or no ) 2.Brain tumour ( versus placebo or phenobarbital) 3.Craniotomy ( versus placebo; or versus 4. Traumatic brain injury versus placebo, no or ) To review the effects of versus placebo, no, phenobarbital or in preventing s associated alcohol or associated craniotomy/tra umatic brain injury Relative risk (ratio of rate in the drug group to rate in the control group) and 95% interval each drug. A probability (p) value the test of no effect (i.e. RR =1) was obtained. All p values are 2 sided and respectively. and physicians assessment of tolerability on a 4 point scale favoured C)Treatment retention: 24 patients on and 34 patients on discontinued the trial prematurely Phenytoin provoked s after craniotomy or traumatic brain injury (RR 0.42;CI Drug identified as effective a condition if the overall test indicates that fewer people assigned to the active had a at the 2-sided 0.05 level. Tandon M et al. serum albuminadjusted levels: an approach predicting drug efficacy in patients Observational study over 6 s 50 patients Male and female Indian patients, aged 15 years 60 years, newly diagnosed epilepsy To investigate whether serum albumin adjusted levels predicted outcome better of serum albumin adjusted levels total levels. Six duration 3 visits at 2 ly intervals. Phenytoin 1. Serum albumin level 2.Serum concentration Post-graduate institute of Medical education and Research Chandigarh, 8

9 epilepsy, suitable developing countries. International Journal of Clinical Pharmacology and Therapeutics. October 2004;42(10):550-5 than total levels. Corrected levels were calculated using the Sheiner- Tozer equation was given at least 1 to allow steady state to be achieved. 3. Corrected level obtained at visit 1 India 9