Prescription patterns of antiepileptic drugs in patients with epilepsy in a nation-wide population

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Summary

Background

Many new antiepileptic drugs (AEDs) have become available in recent years. Investigations of prescription patterns and exposure of AEDs to different patient groups are important regarding drug safety aspects. The aim of this study was to investigate the use of AEDs in epilepsy, with focus on exposure of AEDs, gender and age differences and changes in prescription patterns over time.

Method

The data consisted of all prescriptions of AEDs from Norwegian pharmacies from the Norwegian Prescription Database (NorPD) (2004–2009), which included 44,000–47,000 patients with epilepsy each year. Variables included age, sex, diagnosis-related reimbursement codes and the use of AEDs (defined daily doses (DDDs)).

Results

Twenty two AEDs were in use. There were pronounced age- and gender differences regarding the use of AEDs in epilepsy. The most commonly used drugs were valproate and lamotrigine in children, carbamazepine and lamotrigine in adults, and carbamazepine and phenobarbital in the elderly. Lamotrigine and topiramate were predominantly used in female, and valproate and carbamazepine were predominantly used in male patients, respectively. Eighteen percent used polytherapy with AEDs. Of patients using lamotrigine, 14% received different generic preparations, in spite of the policy of restricted generic substitution. The use of AEDs in 2009 was 6.6 DDDs/1000 inhabitants/day, 49% of the use covered newer AEDs.

Conclusion

The use of AEDs in epilepsy (2004–2009) was investigated in detail. All AEDs showed pronounced age and gender differences. Newer AEDs covered 49% of the total use in 2009. The study contributes to pharmacovigilance, as it offers a basis of knowledge for national decision-making authorities in the field of drug utilization.

Introduction

Antiepileptic drugs (AEDs) consist of a variety of chemical substances, and 14 new AEDs have been marketed during the last 20 years. There is still a lack of documentation of safety aspects regarding many of these drugs, as the use in special patient populations like children, women of childbearing age, and elderly. AEDs are drugs with considerable inter-individual variability and are susceptible to cause adverse effects and drug interactions. AEDs are also extensively used in psychiatric disorders, neuropathic pain and migraine (Tsiropoulos et al., 2006, Savica et al., 2007, Johannessen Landmark et al., 2009), since they have broad-spectrum mechanisms of action (Johannessen Landmark, 2008).

Prescription databases may be used to study specific patient populations, as patients treated for epilepsy. An improved understanding of the treatment of these patients may be obtained and contributes to pharmacovigilance. Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem (WHO, 2002). It aims at enhancing patient care and safety in relation to the use of drugs and the prevention of unintended harm and to contribution to the assessment of the risk-benefit profile of drugs. In this context, improvement of public health and safety in relation to the use of drugs by the provision of reliable, balanced information resulting in more rational use of drugs is of importance (WHO, 2002). This is a relevant and important issue for prescribers, pharmacists and health authorities.

Changes in prescription patterns, exposure of specific drugs to certain patient groups, combination of drugs, generic substitution, potential for drug abuse and the use of AEDs in other disorders than epilepsy are examples of issues that may be investigated in detail using this methodology. In recent years several studies assessing the use of drugs in various populations have been published, using similar methodology restricted to subpopulations or geographical areas (Tsiropoulos et al., 2006, Savica et al., 2007, van de Vrie-Hoekstra et al., 2008, D'Souza et al., 2007) or as a comparison of drug utilization between countries (Hsia et al., 2010). The Norwegian Prescription Database (NorPD) is a validated database covering the whole population and has been used in various pharmacoepidemiological studies (Furu, 2008, Furu et al., 2007, Devold et al., 2010). We have previously used NorPD to study the use of AEDs in various disorders and in patients with epilepsy and psychiatric comorbidity during 2004–2007 (Johannessen Landmark et al., 2009, Karouni et al., 2010). The purpose of the present study was to investigate the use of AEDs in patients with epilepsy in detail in the whole population, with focus on exposure of AEDs, gender and age differences and changes in prescription patterns over time, based upon data from the national database NorPD from 2004 to 2009.

Section snippets

Study material and analyses

The study material consisted of data provided from NorPD including the following variables: gender, year of birth, a pseudonymous patient ID-number, date for delivery of drugs, classification of drugs based upon the ATC-codes, defined daily doses (DDDs), and prescription description (refund or not refund, reimbursement codes) (for definitions, see below). Reimbursement codes related to diagnosis were used as indicators for clinical use, as they are used on prescriptions regarding treatment of

Prescription patterns of AEDs in epilepsy

There were 47,147–43,825 (average 44,611) patients using AEDs from 2004 to 2009. The most recent prevalence of patients treated with AEDs for epilepsy was 0.94% and 0.91% in 2008 and, 2009, respectively. In 2008–2009, the total use of AEDs in epilepsy was 6.88 and 6.6 DDDs/1000 inhabitants/day, respectively. The number of patients using AEDs in epilepsy has decreased by 6–7% during recent years. The use of new AEDs in epilepsy increased from 40 to 49% from 2004 to 2009 (2.80–3.23 DDDs/1000

Prescription patterns of AEDs in epilepsy

The use of population-based data enables the investigation and documentation of the most and least commonly used drugs. The least commonly used drugs include newly marketed drugs that have limited exposure to patients, and other drugs used in specific epilepsy syndromes or patient populations, as vigabatrin and stiripentol in young children. In spite of the limited use of the least commonly used AEDs as compared to the total use of all drugs, it is of importance to document the use of

Conclusions

The use of the most and least commonly used AEDs, 22 in total, based on the use in DDDs/1000 inhabitants/day are presented in the whole population. All AEDs show pronounced age differences. The most commonly used drugs were valproate and lamotrigine in children, carbamazepine and lamotrigine in adults, and carbamazepine and phenobarbital in the elderly. Lamotrigine and topiramate were predominantly used in female patients, and valproate and carbamazepine were predominantly used in male

Disclosure

The authors have no conflicts of interest or any financial disclosures regarding this manuscript.

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