Open Access Original article BMJ Anti epileptic drug

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Open Access, bmjpo first published as 10 1136 bmjpo 2017 000088 on 11 August 2017 Downloaded from http bmjpaedsopen bmj com on October 15 2020 by guest Protected by copyright. countries Tables 1 and 2 describe the prescription rates. of AEDs in Europe and other parts of the world respec. tively In several of the studies sodium valproate was the. most frequently prescribed AED accounting for 7 66. of prescriptions A 9 year Dutch database review of AED. prescriptions reported a sodium valproate prescription. rate of 66 7 table 1 The lowest sodium valproate,prescription rates were 12 and 7 reported in 2003. and 2007 in a Taiwanese population based national, health insurance study8 table 2 Several studies showed. a declining rate of sodium valproate utilisation In the. UK the Clinical Practice Research Datalink CPRD, database study reported a 56 prescription rate for. sodium valproate in 1993 with subsequent decrease to. 50 in 2008 9 Between 2005 and 2009 sodium valproate. prescription rate declined from 58 to 36 in Hong,Kong 10 while a marginal decline from 40 to 38.
between 2000 and 2009 was recorded in a study at the. only children s hospital in Singapore11 figure 2,Carbamazepine was the second most frequently. prescribed AED in several countries tables 1 and 2. Similar to sodium valproate carbamazepine prescrip. tion rates have also shown a declining trend The,Welsh Secure Anonymised Information Linkage SAIL. database recorded a prescription rate of 14 in 2001. compared with 10 a decade later12 figure 2 Similarly. Figure 1 Flow chart of search outcome a 2 decline to 30 was reported in Hong Kong between. 2005 and 2009 10 In Taiwan a minimal decline from 7. in 2003 to 6 in 2007 was reported 8 However in Singa. manual reference searches were also carried out Only pore a 4 increase in carbamazepine prescribing over a. one reviewer carried out the search decade 2000 2009 was reported11 figure 2. Inclusion and exclusion criteria Phenobarbital utilisation was highly variable in different. All paediatric national or regional database studies and countries with prescription rates varying between 1. surveys were included irrespective of language of publi and 65 Phenobarbital prescribing has been higher in. cation Single centre studies were excluded Mixed Asia accounting for 8 13 and 24 of all AEDs used. population studies in which the paediatric data were in Hong Kong 2009 10 Singapore 2009 11 and Taiwan. presented were also included Paediatrics was defined 2007 8 respectively table 1 compared with 2 and 5. as any patient 18 years old or as defined by the respec in the UK 2008 9 and the Netherlands 2006 7 respec. tive authors Studies in which the percentage of AED tively table 2 Phenytoin prescriptions ranged between. utilisation was not presented or could not be calculated 1 and 4 in all studies with only marginal changes in. were excluded Two reviewers determined eligibility for prescription rates observed in the last two decades tables. inclusion 1 and 2,Lamotrigine was the most frequently prescribed. Data extraction new generation AED in several countries with prescrip. Data extracted from each study included year of study tion rates ranging from 1 to 34 The highest. country of study setting age of patients study design prescription rate of 34 was recorded in a 2000 2007. number of study participants the type of AED and Norwegian Prescription Database study 13 The UK CPRD. percentage of children receiving AED Only one reviewer 1993 2008 study and the Welsh SAIL database study. carried out the data extraction 2000 2010 showed rising prescription prevalence. with prescribing increasing from 4 and 11 in 2000 to. 22 and 21 in 2010 respectively However studies in, Results Hong Kong and Singapore reported a marginal decline. Twenty one studies were identified Five were excluded in lamotrigine prescription rate In Taiwan a 9 decline. from the review as the data were collected before in prescription rate was reported between 2003 and 2007. 2005 online supplementary table 1 These were figure 3. excluded because they were unlikely to adequately Levetiracetam prescription rate increased by 10. capture new AEDs Monotherapy was the most common within 8 years after 2000 in the UK9 and 8 within 10. regimen varying between 58 and 94 in different years in Wales 12 In Taiwan the prescription rate of. 2 Egunsola O et al BMJ Paediatrics Open 2017 1 e000088 doi 10 1136 bmjpo 2017 000088. Table 1 Antiepileptic drugs prescription rates in Europe. Country Ref Year Patients n Poly Prevalence CBZ PHT PBT LTG TPM LEV OXC Others. Croatia 2005 258 22 51 17 17 13 28, Germany40 2004 2006 13 197 25 41 32 7 5 15 6 4 10 STM 11 ETX 1.
Germany31 2009 2361 42 52 24 11 9 7 7, Italy 2003 2010 10 255 28 64 14 0 2 8 1 2 2 3 ETX 1 CZP 0 5. Italy28 2001 2005 375 39 6 11 4 5 VGB 4,felbamate 0 3. The Netherlands7 1997 2005 1527 20 22 66 23 2 5 16 4 3. The Netherlands 2001 2005 11 2 3 8 VGB 3 GBP 8, Egunsola O et al BMJ Paediatrics Open 2017 1 e000088 doi 10 1136 bmjpo 2017 000088. pregabalin 2, Norway13 2004 2009 4015 18 91 42 19 2 0 34 10 12 8 CZP 7 GBP 2. UK 1993 2008 27 56 50 4 1 3 2 4 22 0 10,UK28 2001 2005 578 30 14 7 4 2 VGB 2 GBP 1.
Wales12 2000 2010 992 76 61 14 10 11 21 0 8, Data for empty cells not available Data before and after slash represent the earliest and most recent data for the study respectively. AED prevalence per 10 000 persons,Prevalence for last year of study. Incident monotherapy users,Prevalence per 10 000 person years. CBZ carbamazepine CZP clonazepam ETX ethosuximide GBP gabapentin LEV levetiracetam LTG lamotrigine OXC oxcarbazepine PBT phenobarbital PHT phenytoin poly. polytherapy STM sulthiame TGB tiagabine TPM topiramate VGB vigabatrin VPA sodium valproate. Open Access, bmjpo first published as 10 1136 bmjpo 2017 000088 on 11 August 2017 Downloaded from http bmjpaedsopen bmj com on October 15 2020 by guest Protected by copyright. Open Access, Table 2 Antiepileptic drugs prescription rates in other parts of the world.
Ref Year Patients n Poly Prevalence VPA CBZ PHT PBT LTG TPM LEV OXC Others. Jordan 2014 694 33 51 33 4 3 3 4 1,Cuba42 2009 923 6 52 37 52 4 5 1 1 CZP 3 ETX 0 4. Hong Kong10 2005 2009 21 58 36 32 30 3 3 7 8 8 7 7 7 2 7 1 3 CLB 12 14 ETX. 0 3 0 5 VGB 2 2, Singapore11 2000 2009 37 40 38 23 27 3 4 29 13 3 2 0 3 0 6 VGB 1 1. South 2007 24 32 16 17 18, Taiwan8 2003 2007 138 12 7 7 6 2 1 65 24 19 10 21 9 0 18 29 9 VGB 44 36 GBP. USA14 1999 2006 4666 27 46 29 13 8 15 16 8 28 GBP 11 ETX 5. ZNS 3 TGB 1, Data for empty cells unavailable Data before and after slash represent the earliest and most recent data for the study. Prevalence per 10 000 persons,Prevalence in the final year of study.
CBZ carbamazepine CLB clobazam CZP clonazepam ETX ethosuximide GBP gabapentin LEV levetiracetam LTG lamotrigine OXC oxcarbazepine PBT phenobarbital PHT phenytoin. poly percentage polytherapy STM sulthiame TGB tiagabine TPM topiramate VGB vigabatrin VPA sodium valproate ZNS zonisamide. Egunsola O et al BMJ Paediatrics Open 2017 1 e000088 doi 10 1136 bmjpo 2017 000088. bmjpo first published as 10 1136 bmjpo 2017 000088 on 11 August 2017 Downloaded from http bmjpaedsopen bmj com on October 15 2020 by guest Protected by copyright. Open Access, bmjpo first published as 10 1136 bmjpo 2017 000088 on 11 August 2017 Downloaded from http bmjpaedsopen bmj com on October 15 2020 by guest Protected by copyright. levetiracetam rose from 0 in 2003 to 18 in 20078, figure 3 while topiramate prescription rate in Taiwan. decreased from 21 in 2003 to 9 four years after,Between 1999 and 2006 oxcarbazepine was 28 in the. USA 14 In 2007 data from the South Korean health insur. ance database reported oxcarbazepine as the second. most frequently prescribed AED accounting for 18 of. all AEDs prescribed 15, In most countries vigabatrin utilisation varied between. 1 and 4 However prescription was high in Taiwan,between 2003 44 and 2007 36 In 2007 it was.
the most frequently prescribed AED in Taiwan and,the second most prescribed in 2003 In Hong Kong. vigabatrin prescription rate was 2 in 2005 and 2009. respectively table 2,Discussion, Sodium valproate was the most frequently prescribed. AED in children in most countries The broad spectrum. of activity of the drug may be responsible for its continued. preference for the management of paediatric epilepsy. Although current guidelines recommend both sodium, valproate and carbamazepine as first line antiepileptic. agents 16 lamotrigine oxcarbazepine and levetiracetam. utilisation is growing 14 This study showed a declining. prevalence of all old generation AEDs and a mixed trend. in the utilisation rates of lamotrigine and topiramate. Figure 2 Sodium valproate and carbamazepine utilisation There was a general increase in the use of levetiracetam. trends Putignano et al17 attributed the increase in new AED util. isation in a region in Italy to increased levetiracetam use. There was generally a mixed trend with carbamazepine. utilisation in countries with high Han ethnic population. Singapore Hong Kong and Taiwan Carbamazepine util, isation was high in Hong Kong and Singapore but low in. Taiwan The utilisation of oxcarbazepine which is struc. turally similar to carbamazepine declined from 29, to 9 between 2003 and 2007 in Taiwan It is unclear.
how recommendations for genetic testing18 19 in this. population have impacted on carbamazepine and oxcar. bazepine use Recent data from a teaching hospital in. the Shanghai region of China showed a 30 and 1 for. oxcarbazepine and carbamazepine respectively 20 The. high rate of use of oxcarbazepine in China is surprising. in view of the known predisposition of this population to. the development of Stevens Johnson syndrome 21 22, The rising prevalence of new generation AEDs may be. attributed to their increased utilisation for other indi. cations such as psychiatric disorders lamotrigine 23. and pain gabapentin and oxcarbazepine 24 25 One, adult study reported a 55 fold increase in non seizure. gabapentin prescription over 15 years in Canada 26 A. recent safety alert by the UK Medicines and Healthcare. products Regulatory Agency MHRA is likely to further. reduce the utilisation of valproate in the UK The report. showed that up to 40 of children exposed in utero to. the drug are at a high risk of serious developmental disor. Figure 3 Lamotrigine and levetiracetam utilisation trends ders and up to 10 at risk of congenital malformations 27. Egunsola O et al BMJ Paediatrics Open 2017 1 e000088 doi 10 1136 bmjpo 2017 000088 5. Open Access, bmjpo first published as 10 1136 bmjpo 2017 000088 on 11 August 2017 Downloaded from http bmjpaedsopen bmj com on October 15 2020 by guest Protected by copyright. Consequently the MHRA recommended the avoidance Competing interests None declared. of valproate prescription to female children female Provenance and peer review Not commissioned externally peer reviewed. adolescents women of childbearing potential or preg Open Access This is an Open Access article distributed in accordance with the. nant women unless other treatments are ineffective or Creative Commons Attribution Non Commercial CC BY NC 4 0 license which. not tolerated 27 permits others to distribute remix adapt build upon this work non commercially. and license their derivative works on different terms provided the original work is. The prescribing patterns of AEDs in children vary properly cited and the use is non commercial See http creativecommons org. among countries because of differences in healthcare licenses by nc 4 0. systems cost of medicines availability of drugs as well Article author s or their employer s unless otherwise stated in the text of the. as local and national epilepsy management guidelines 28 article 2017 All rights reserved No commercial use is permitted unless otherwise. New generation AEDs are generally more expensive expressly granted. hence prescriptions are less prevalent in low income. countries and countries with poor health insurance. coverage For instance phenobarbital accounted for References. about two thirds of AED prescriptions in a large Ethio 1 Weijenberg A Offringa M Brouwer OF et al RCTs with new. pian adult study 2010 2012 while 30 of prescriptions antiepileptic drugs in children a systematic review of monotherapy. studies and their methodology Epilepsy Res 2010 91 1 9. were for phenytoin 29 A similar trend was reported in an 2 Marson AG Al Kharusi AM Alwaidh M et al The SANAD study. Indian study in which over 95 of prescriptions were of effectiveness of carbamazepine gabapentin Lamotrigine. oxcarbazepine or topiramate for treatment of partial epilepsy an. old generation drugs 30 In high income countries the cost unblinded randomised controlled trial Lancet 2007 369 1000 15. of some new generation AEDs is sometimes not covered 3 Kimland E Rane A Ufer M et al Paediatric adverse drug reactions. by the national health insurance or subsidy programmes reported in Sweden from 1987 to 2001 Pharmacoepidemiol Drug. Saf 2005 14 493 9, In Singapore for instance a 2012 study by Tan et al11 4 Loke YK Use of databases for clinical research Arch Dis Child. reported that only sodium valproate carbamazepine 2014 99 587 9. 5 Clavenna A Bonati M Differences in antibiotic prescribing in. phenobarbital and phenytoin were subsidised by the paediatric outpatients Arch Dis Child 2011 96 590 5. government Similarly Hamer et al31 also reported that 6 Clavenna A Bonati M Drug prescriptions to outpatient children a. Antiepileptic drugs pr escription rates in other parts of the world Country Ref Year Patients n Poly Prevalence VPA CBZ PHT PBT LTG TPM LEV OXC Others Jordan 41 2014 694 33 51 33 4 3 3 4 1 Cuba 42 2009 923 6 52 37 52 4 5 1 1 CZP 3 ETX 0 4 Hong Kong 10 2005 2009

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