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Correlation between prescribed daily dose, seizure freedom and defined daily dose in antiepileptic drug treatment

Abstract

Background Although defined daily doses (DDD) for antiepileptic drugs (AED) have been assigned only in combination therapy, based on the literature, most patients take them in monotherapy. Furthermore, discrepancies between DDD and prescribed daily dose (PDD) were observed. Objective First, to determine PDDs of AEDs and to reveal PDD/DDD ratio among seizure free versus not seizure free patients in everyday clinical practice. Second, to test the applicability of 75% cut-off of DDD to achieve seizure freedom. Furthermore, to find out what factors might influence PDD. Setting Outpatient data files at a Hungarian university hospital were studied. Methods A retrospective, 20-year cross-sectional database was compiled from 1282 epileptic outpatients’ files. Main outcome measure Seizure freedom and PDD were used as outcome measures. Results The mean DDD% of all prescribed AEDs increased steadily from monotherapy, through bitherapy towards polytherapy (p < 0.0001). Most seizure free patients took AEDs in doses in the range of ≤75% of DDDs in monotherapy and bitherapy. Older AEDs (carbamazepine and valproate) were given in a significantly higher mean dose in bitherapy in the seizure free group. Among the newer types, only levetiracetam and lamotrigine had a significantly higher DDD% in mono-, bi-, and polytherapy. Confirmed by logistic regression analysis, gender, age, type of epilepsy, and number of AEDs had a significant impact on the value of 75% DDD. Conclusion No significant unfavourable impact of the lower ratio of PDD/DDD on the outcome of achieving seizure freedom has been confirmed. As a measure of seizure freedom, 75% of DDD may be used, although individual therapy must be emphasised. Precisely quantified DDD would provide a more accurate calculation of other derived values.

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Acknowledgements

The authors thank the medical staff for active participation in the treatment.

Funding

This study was supported by the following grants: Grant of the Hungarian Ministry of Health (No. ETT 238/2006) and Research Fellowship of the Faculty of Medicine, University of Debrecen, 2012–2016 (OSTRAT/436/2012).

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Correspondence to László Horváth.

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The authors declare that they have no conflict of interest.

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Horváth, L., Fekete, K., Márton, S. et al. Correlation between prescribed daily dose, seizure freedom and defined daily dose in antiepileptic drug treatment. Int J Clin Pharm 39, 459–467 (2017). https://doi.org/10.1007/s11096-017-0447-1

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Keywords

  • DDD
  • Drug utilization review
  • Epilepsy
  • Hungary
  • PDD