Changes in medication associated with epilepsy‐related hospitalisation: a case‐crossover study

Abstract

SUMMARYAim To assess the association between changes in medication and epilepsy-related hospitalisation. Methods Data were obtained from the PHARMO Record Linkage System (Jan 1998 to Dec 2002). We conducted a casecrossover study among patients with a first epilepsy-related hospital admission who had continuously used at least one antiepileptic drug (AED) during a 28-week period before admission. For each patient, changes in medication in a 28-day window before hospitalisation were compared with changes in four earlier 28-day windows. Evaluated changes were: changes in AEDs (pattern and dosage), changes in interacting co-medication and changes in non-interacting co-medication (i.e. introduction of noninteracting drugs). The strength of the association between changes in medication and epilepsy-related hospitalisation was estimated using conditional logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CI). Results Out of 1185 patients with a first epilepsy-related hospitalisation, 217 patients met the inclusion criteria. Of the changes in antiepileptic therapy, discontinuation showed a trend towards an increased risk of hospitalisation (OR: 2.57; 95%CI: 0.81-8.17). Drug interactions influencing antiepileptic therapy rarely occurred. Introduction of three or more non-interacting drugs was significantly associated with epilepsy-related hospitalisation (OR: 4.80; 95%CI: 2.12-10.87). Of individual drugs, addition of antimicrobial agents was significantly associated with epilepsy-related hospitalisation (OR: 1.99; 95%CI: 1.06-3.75). Conclusions Changes in AED therapy were not significantly associated with epilepsy-related hospitalisation and few drug interactions influencing antiepileptic therapy occurred. However, patients starting three or more new non-AEDs had a nearly five times increased risk of epilepsy-related hospital admission.

Case‐crossover study design in pharmacoepidemiology: systematic review and recommendations

“…Of 836 unique articles identified, 99 pharmacoepidemiologic studies were eligible: 20 methodological contributions, 9 review papers, and 70 empirical applications, Figure . Of the 70 pharmacoepidemiologic empirical applications, 47% were identified by all 3 searches, 36% were identified in both MEDLINE and EMBASE but not the Web of Science citation search, and 10% were identified uniquely from the Web of Science seminal paper citation search, Figure .…”

The case-crossover study design in pharmacoepidemiology

“…The case-crossover study design has been used to estimate drug effects in a wide range of pharmacoepidemiology studies. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Outcomes have tended to be acute events such as motor vehicle crashes, 12,19,21 death, 26,30 and myocardial infarction. 25,27,30 Exposures have typically been a pharmacological agent given for short time periods, such as vaccines, 22 antibiotics, 29 and psychotropic medication prescriptions.…”

Requirements for generic anti-epileptic medicines: a regulatory perspective

“…Handoko et al [ 36 ] indicated that patients who started, besides their normal anti-epileptic medication, several non-antiepileptic comedications, experienced a 5-times increased chance of an epilepsy-related hospitalization. Although at this moment a causal relationship still needs to be confirmed, it is an illustration of the complexity of the issue.…”