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Purpose: Antiepileptic drugs (AEDs) are increasingly used, and knowledge about adverse effects is scarce based on clinical studies. The purpose of the present study was to characterise adverse effects reports of AEDs in Norway relative to changes in utilisation in various indications from population-based data to elucidate important safety aspects of use of AEDs., Methods: Aggregated data of adverse effects reported for AEDs in Norway from the EudraVigilance-database (2004-2013) in addition to indication-specific use of AEDs during 2004-2015 from the Norwegian Prescription Database were used., Results: The use of AEDs increased twofold the last decade due to use in psychiatry and neuropathic pain: lamotrigine, pregabalin, gabapentin, valproate, and carbamazepine. There were 1593 adverse effects reported (403 Individual Case Safety Reports, 2/3 women), 0-95 years (mean 46). Most adverse effects were reported for pregabalin (593), carbamazepine (265), lamotrigine (206), gabapentin (144), and valproate (119), where pregabalin had by far the highest reports in relation to the number of users. The most frequently reported adverse drug effects included rash, dizziness, cross-sensitivity reactions, and pyrexia. Overall, nervous system disorders constitute the largest organ class with the majority of the reports. Reporting of fatal outcomes is mandatory, and sudden unexplained death in epilepsy (SUDEP) was reported in 34 occasions., Conclusions: This study demonstrates that most adverse effects reported concerned AEDs increasingly used in non-epilepsy indications: neuropathic pain (pregabalin, gabapentin, carbamazepine) and psychiatry (lamotrigine, valproate, carbamazepine). Pregabalin had the highest prevalence of adverse effects reported in relation to number of users. This elucidates an important part of pharmacovigilance for improved safety and considerations in clinical practice.

Purpose: The purpose of this study was to investigate changes in utilisation of antiepileptic drugs (AEDs) in epilepsy and non-epilepsy disorders in Norway and furthermore to study the retention rates of the most commonly used AEDs in these indications in long-term use., Methods: The data consisted of all prescriptions of AEDs from Norwegian pharmacies in the Norwegian Prescription Database (NorPD) (2004-2012). Variables included anonymous data regarding age, gender, diagnosis specific reimbursement codes and utilisation of AEDs., Results: In recent years (2008-2012), the utilisation of AEDs in non-epilepsy disorders accounted for 45-53 % of the total use. In epilepsy, the most commonly used AED was lamotrigine, followed by levetiracetam, carbamazepine and valproate. Lamotrigine was also the predominant AED used in psychiatry, while pregabalin and gabapentin were mostly used in neuropathic pain. In migraine, topiramate predominated but accounted for <1 % of the total utilisation of AEDs. The majority of prescriptions were by general practitioners and only 20 % by specialists. Regardless of indication, newer AEDs had higher retention rates (34-48 %) and were used for a longer period before discontinuation., Conclusions: The use of AEDs in non-epilepsy disorders is increasing and accounted for 53 % in 2012. Newer AEDs were predominantly used and demonstrated higher retention rates than older AEDs in all indications. This nationwide study demonstrates an increased exposure to AEDs in new patient groups, and details in prescription patterns and clinical and safety considerations should be closely monitored. This contributes to long-term post-marketing data of AED and accordingly improved pharmacovigilance.

Purpose: Patients with epilepsy often suffer from concomitant psychiatric disorders. Treatment patterns and the extent of comorbidity are insufficiently investigated and appropriate methods are scarce. The purpose of the study was to estimate the prevalence of psychiatric comorbidity in patients with epilepsy and to investigate prescription patterns of drugs prescribed for psychiatric disorders in epilepsy., Methods: Prescription data from the Norwegian Prescription Database (NorPD) regarding the use of CNS-active drugs included anonymous data from almost 190,000 patients and 1.1-1.3 million prescriptions per year (2004-2007). Searches were based upon use of specific drugs, defined daily doses, number of patients, prescriptions, gender, and age. Reimbursement codes related to psychiatric diagnosis were used as indicators for clinical use., Results: The prevalence of psychiatric comorbidity in patients with epilepsy was estimated to be 32%. There were 56% women and 44% men participating in the study. Among patients using antidepressants two thirds were women, but no gender differences were seen with antipsychotic medication. Antidepressants and antipsychotics were used 3.4 (20.9%) and 5.8 (13.4%) times more frequently than in the general population, accounting for 7.88 and 1.99 defined daily doses (DDDs)/1,000 inhabitants/day/year respectively. Lamotrigine was the most commonly used antiepileptic drug (AED) in epilepsy, accounting for 33% of the use of AEDs (in total 5.65 DDDs/1,000 inhabitants/day/year). The use of benzodiazepines was 9.55 DDDs/1,000 inhabitants/day/year. The patients had complex pharmacotherapy with two to eight concomitant drugs., Conclusion: The present study gives an estimate of psychiatric comorbidity of 32% in patients with epilepsy in a nation-wide population. The pharmacotherapy in this patient population is complex. The results provide valuable data on prescription patterns that contribute to pharmacovigilance on a national scale.

Objective: To discuss the potential value of therapeutic drug monitoring (TDM) of the new antiepileptic drugs gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin and zonisamide., Methods: A review of studies of the relationship between plasma concentrations and effects of new antiepileptic drugs is provided. Furthermore, the potential value of TDM of these drugs is discussed in relation to their mode of action and their pharmacokinetic properties. The various methods that are available for analysing plasma concentrations of the new antiepileptic drugs are also briefly reviewed., Results: The available information on the relationship between plasma concentrations and effects of the new drugs is scarce. For most drugs, wide ranges in concentrations associated with seizure control are reported, and a considerable overlap with drug levels among non-responders and also with concentrations associated with toxicity is often noted. However, very few studies have been designed primarily to explore the relationship between drug plasma concentrations and effects. Consequently, there are no generally accepted target ranges for any of the new antiepileptic drugs. Although the available documentation clearly is insufficient, the pharmacological properties of some of the drugs, in particular lamotrigine, zonisamide and, possibly, oxcarbazepine, topiramate and tiagabine, suggest that they may be suitable candidates for TDM., Conclusion: TDM of some of the new antiepileptic drugs may be of value in selected cases, although routine monitoring in general cannot be recommended at this stage. Further systematic studies designed specifically to investigate concentration-effect relationships of the new antiepileptic drugs are urgently needed.