View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Seizure 21 (2012) 466–470 Contents lists available at SciVerse ScienceDirect Seizure jou rnal homepage: www.elsevier.com/locate/yseiz Trends in antiepileptic drug utilisation in UK primary care 1993–2008: Cohort study using the General Practice Research Database a b b a a, Jennifer M. Nicholas , Leone Ridsdale , Mark P. Richardson , Mark Ashworth , Martin C. Gulliford * a King’s College London, Department of Primary Care and Public Health Sciences, UK b King’s College London Department of Clinical Neuroscience, Institute of Psychiatry, UK A R T I C L E I N F O A B S T R A C T Article history: Purpose: To describe changes in utilisation of antiepileptic drugs (AED) by people with epilepsy in the Received 20 March 2012 United Kingdom during 1993–2008. Received in revised form 27 April 2012 Methods: Cohort study of 63,586 participants with epilepsy and prescribed AEDs from 434 UK family Accepted 29 April 2012 practices. Prescriptions for different AEDs and AED combinations were evaluated by calendar year, gender and age group. Keywords: Results: Total follow-up was 361,207 person-years, with 282,080 person-years treated with AEDs and Epilepsy 79,126 person-years untreated. AED monotherapy accounted for 72.6% of treated person years of follow- Antiepileptic drugs up. Carbamazepine and valproates were among the most commonly used medications throughout 1993– Anticonvulsants 2008. Phenytoin accounted for 39.5% of treated person-years in 1993 declining to 18.3% by 2008. Use of Drug utilisation Primary care barbiturates declined from 14.3% in 1993 to 6.0% in 2008. In contrast between 1993 and 2008 there were substantial increases in the use of lamotrigine (2.0% to 17.0%) and to a lesser extent levetiracetam (0% to 8.6%). Newer AEDs were more frequently prescribed to younger participants, especially women aged 15– 44 years, while older adults were more likely to be prescribed longer established AEDs. In 1993, 201 different AED combinations were prescribed, increasing to 500 different combinations in 2008. Combinations of sodium valproate and carbamazepine were frequent throughout, while sodium valproate and lamotrigine was frequent in 2008. Conclusions: Utilisation of newer AEDs in UK primary care has increased between 1993 and 2008 with increasing use of diverse combinations of AEDs. The data quantify exposure to AEDs relevant to planning analytical pharmaco-epidemiological studies, as well as providing information to inform prescribing policies. ß 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. 3,4 1. Introduction aim of increasing efficacy and reducing side effects. Safety for 5 use in pregnancy is an important concern in younger women. The prevalence of epilepsy, and treatment with antiepileptic However, these newer drugs are generally more costly because drugs (AEDs), is increasing. A large cohort study from UK primary they are not initially available in generic formulations. Initial drug care showed that the prevalence of persons ever diagnosed with selection is often the responsibility of specialists in neurology, epilepsy and prescribed antiepileptic drugs on one or more internal medicine, psychiatry, paediatrics or elderly care. Primary 1 occasions increased from 0.9% to 1.2% between 1993 and 2007. care physicians may lack experience in selecting and adjusting the Prescription of antiepileptic drugs remains the mainstay of seizure dosage of newer drugs, nevertheless the continuation of anti- 2 prevention in people with epilepsy. Side effects to AEDs, including epilepsy drugs is largely managed by them. both dose-related side effects and idiosyncratic adverse drugs Drug utilisation studies in epilepsy serve several purposes. Such reactions, represent an important limiting factor in epilepsy studies provide data on the prevalence of exposure to different treatment. Older AEDs generally have a less favourable safety AEDs in a population with epilepsy in order to inform pharmaco- 2 profile. Several newer AEDs have now been introduced with the epidemiological and drug safety studies in AEDs. Drug utilisation studies also provide descriptive information on the process of diffusion of newer AEDs into clinical practice in primary care in the UK, as well as quantitative estimates for the decline in prescribing * Corresponding author at: Department of Primary Care and Public Health of older AEDs. This information may be used to inform clinical Sciences, King’s College London, Capital House, 42 Weston St, London SE1 3QD, UK. prescribing policies. The present paper therefore reports a Tel.: +44 (0) 207 848 6631. E-mail address: [email protected] (M.C. Gulliford). descriptive epidemiological study of antiepileptic drug utilisation 1059-1311/$ – see front matter ß 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.seizure.2012.04.014 J.M. Nicholas et al. / Seizure 21 (2012) 466–470 467 by persons with epilepsy. The study aimed to describe the each calendar year by age group (0–14, 15–44, 45–64, 65+ years) utilisation of all AEDs that were available in the United Kingdom and gender. For each year, age group and gender category, we then between 1993 and 2007. calculated: (1) the number of person-years of treatment with each type of AED; (2) number of person-years of treatment with AED 2. Methods monotherapy, two concurrent AEDs, three concurrent AEDs, and four or more concurrent AEDs. The trends in types and number of This cohort study utilised data from family practices in the UK AEDs, and AED combinations, prescribed were then presented as a contributing to the UK General Practice Research Database (GPRD) proportion of AED treated person years for all participants and by between 1 January 1993 and 15 October 2008. For entry into the age and gender. GPRD, family practice data must be up to standard (UTS) for research as set out by the GPRD group. Participants were included 3. Results in the study cohort if they had ever had a recorded diagnosis of epilepsy and also had received one or more prescriptions for AEDs The cohort of participants included 63,586 participants from after they were registered with a GPRD practice. Date of onset of 434 family practices. Total follow-up was 361,207 person-years, of epilepsy was defined as the earliest date at which a participant had which 282,080 person-years were treated with AEDs and 79,126 a recorded diagnosis of epilepsy or prescription of AEDs. person-years not treated with AEDs. The median duration that Participant follow-up started on the date of first AED individual participants remained in the study was 4.50 person- prescription after the later of: date of onset of epilepsy, date of years (inter-quartile range (IQR): 1.74, 8.67). The median number registration with a GPRD practice, date at which the practice began of person-years that were AED treated was 2.97 (IQR: 0.98, 6.86), contributing UTS data to GPRD, or 1 January 1993. Participant with a median of 0.66 (IQR: 0.14, 2.75) not AED treated. Table 1 follow-up was censored if the participant died or transferred out of gives the characteristics of the participants who were on follow-up a GPRD practice, or at the last date at which their practice at the start of each calendar year from 1993 to 2008. There are contributed UTS data to GPRD. Using this definition, participants fewer years of follow-up in 2008 because GPRD data were only remained on follow-up after ceasing to receive AED prescriptions. available for part of this year. Treatment was ascertained from recorded prescriptions issued Participants were most commonly treated with AED mono- to patients by their family practice. AEDs were identified from the therapy, which accounted for 72.6% of person-years of treated unique product codes that are used to code prescriptions into follow-up. Participants were treated with two AEDs during 21.9% primary care electronic records. The following categories of of person-years of follow-up, three medications for 4.7% of follow- medication were used: barbiturates (phenobarbital, phenobarbital up and four or more medications for 0.8% of follow-up. The most sodium, methylphenobarbital); valproates (valproic acid, sodium commonly used medications were carbamazepine, valproates and valproate); phenytoin (phenytoin, phenytoin sodium); fospheny- phenytoin, which were all utilised for greater than 25% of AED toin sodium; carbamazepine; oxcarbazepine; topiramate; primi- treated follow-up (Table 2). Three medications (mesuximide, done; ethosuximide; mesuximide; clobazam; clonazepam; beclamide, lacosamide) were not prescribed to any participants gabapentin; pregabalin; vigabatrin; tiagabine; sultiame; zonisa- during follow-up. An additional four medications (sultiame, mide; beclamide; lamotrigine; lacosamide; levetiracetam; rufina- rufinamide, fosphenytoin sodium, stiripentol) were used for less mide; stiripentol. To calculate person-years of exposure to each than 5 person-years. AED, participants were considered currently treated with an AED There was little change in the number of concurrent AEDs for the 90 days following each prescription. Previous analyses prescribed to patients between 1993 and 2008. The types of AED show that precise duration of prescription cannot be reconstructed that were prescribed showed substantial changes from 1993 to for a significant proportion of GPRD prescriptions. A period of 90 2008 (Figs. 1 and 2). Carbamazepine and valproates were among days was established as an average treatment interval from a the most commonly used medications throughout 1993–2008. previous study of participants with diabetes. Although phenytoin was the medication with greatest use in 1993 To examine trends in AED utilisation we examined both at 39.5% of treated person-years, treatment with phenytoin number of concurrent AEDs prescribed and type of AED prescribed declined sharply to 18.3% of treated person-years by 2008.