Pål G. Larsson

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

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.

Antiepileptic drugs in epilepsy and other disorders—A population-based study of prescriptions

PURPOSE The aim of the study was to quantify the use of antiepileptic drugs (AEDs) in epilepsy and other indications in a nation-wide population using a prescription database. MATERIALS AND METHODS Prescription data of AEDs were collected from the Norwegian Prescription Database for the period 2004-2007, including 5.1 million prescriptions from 144,653 patients, all having at least one prescribed and dispensed AED. Diagnosis-related reimbursement codes were used as indicators for clinical use. RESULTS Of the AEDs used, 71% was in epilepsy, 15% in psychiatry, 13% in neuropathic pain, and <1% in migraine, trigeminus neuralgia and cancer adjuvance. The use in epilepsy increased steadily from 7.0 to 7.5 DDDs/1000 inhabitants/day (7%) from 2004 to 2007. The use of AEDs in other indications increased considerably more from 2004 to 2007: Neuropathic pain to 1.40 DDDs/1000 inhabitants/day (360%), psychiatry to 1.59 (200%), and migraine to 0.005 (642%). The prevalence of AED users increased and in 2007 it was 0.97% in epilepsy, 0.8% in neuropathic pain, 0.33% in psychiatry and 0.001% in migraine. In 2007, 49% of the AEDs used in epilepsy were a new drug, carbamazepine, lamotrigine and valproate being most frequently used. New AEDs were used in 96% in migraine prophylaxis, 94% in neuropathic pain, and 64% in psychiatry. CONCLUSIONS Based on a nation-wide prescription database, this study quantifies the wide and increasing use of AEDs, in particular the newer drugs.

Does physical exercise influence the occurrence of epileptiform EEG discharges in children

Summary: Purpose: To determine if, and how, epileptiform EEG discharges in children were influenced by physical exercise.

Psychiatric comorbidity in patients with epilepsy: a population-based study

PurposePatients 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.MethodsPrescription 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.ResultsThe 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.ConclusionThe 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.

Reducing the bias of causality measures

Measures of the direction and strength of the interdependence between two time series are evaluated and modified to reduce the bias in the estimation of the measures, so that they give zero values when there is no causal effect. For this, point shuffling is employed as used in the frame of surrogate data. This correction is not specific to a particular measure and it is implemented here on measures based on state space reconstruction and information measures. The performance of the causality measures and their modifications is evaluated on simulated uncoupled and coupled dynamical systems and for different settings of embedding dimension, time series length, and noise level. The corrected measures, and particularly the suggested corrected transfer entropy, turn out to stabilize at the zero level in the absence of a causal effect and detect correctly the direction of information flow when it is present. The measures are also evaluated on electroencephalograms (EEG) for the detection of the information flow in the brain of an epileptic patient. The performance of the measures on EEG is interpreted in view of the results from the simulation study.

The effect of acupuncture in chronic intractable epilepsy

We examined the effect of acupuncture on epileptic seizures in humans in a controlled clinical setting. Treatment was administered by two Chinese professors of acupuncture. Effect was measured by change in seizure frequency. Twenty-nine patients with chronic intractable epilepsy completed the study. They were randomized in two groups; 15 were given classical acupuncture and 14 were given sham acupuncture. There was a reduction in seizure frequency in both groups, which did not reach a level of statistical significance. There was also an increase in the number of seizure-free weeks in both groups, which reached a level of significance in the sham group. Thus, we have not been able to prove a beneficial effect of acupuncture in chronic intractable epilepsy.

Acupuncture in intractable epilepsy: lack of effect on health-related quality of life

The objective of this study was to assess the effect on health-related quality of life of acupuncture and sham acupuncture as adjunctive treatment in intractable epilepsy. We performed a randomized controlled trail with two parallel treatment arms at The National Center for Epilepsy in Norway, a comprehensive epilepsy center. Thirty-four patients with long-standing drug resistant epilepsy completed the study. The intervention consisted of 20 acupuncture treatments (bilateral needling of three acupoints plus one or two individually chosen points) or sham acupuncture (bilateral needling with smaller needles of three points outside the traditional meridians) over 8 weeks. The main outcome measures were changes in mean health-related quality of life scores for the two groups after 8 weeks, using the 89-item Quality of Life in Epilepsy (QOLIE-89) questionnaire. We found no difference between the acupuncture and sham acupuncture groups in score changes in any dimension of the QOLIE-89 questionnaire, despite testing a large number of dimensions. We also found no change in QOLIE-89 scores between baseline and 8 weeks in either groups. In conclusion, we could not demonstrate a significant effect of traditional acupuncture or sham acupuncture on the health-related quality of life of patients with intractable epilepsy.

The effect of levetiracetam on focal nocturnal epileptiform activity during sleep — A placebo-controlled double-blind cross-over study

Electric Status Epilepticus during Sleep (ESES) occurs in children with and without epilepsy. It may be related to disturbances as autism spectrum disorder, attention-deficit hyperactivity disorder and acquired aphasia (Landau-Kleffner syndrome). Antiepileptic drug (AED) treatment has been reported in small studies without placebo control. This study was designed to assess AED effect in a placebo-controlled double-blind cross-over study. Levetiracetam (LEV) was chosen based on clinical evidence. Eighteen patients fulfilled the inclusion criteria. The mean spike index at baseline was 56, falling to a mean of 37 at the end of the LEV treatment period. Assessed with a 2-way ANOVA, there is a significant treatment effect (p<0.0002). To the best of our knowledge, this is the first placebo-controlled double-blind cross-over study for any AED in patients with ESES. The effect of LEV is comparable with its effect in treatment of epileptic seizures.

Fast evaluation of interictal spikes in long-term EEG by hyper-clustering

Purpose:  The burden of reviewing long‐term scalp electroencephalography (EEG) is not much alleviated by automated spike detection if thousands of events need to be inspected and mentally classified by the reviewer. This study investigated a novel technique of clustering and 24‐h hyper‐clustering on top of automated detection to assess whether fast review of focal interictal spike types was feasible and comparable to the spikes types observed during routine EEG review in epilepsy monitoring.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe

In 2014 the European Union–funded E‐PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers.