Correlation Between Prescribed Daily Dose, Seizure Freedom and Defined Daily Dose in Antiepileptic Drug Treatment

Overview

Journal Int J Clin Pharm

Publisher Springer

Specialties Pharmacology
Pharmacy

Date 2017 Mar 4

PMID 28255953

Citations 6

Authors

Laszlo Horvath

Klara Fekete

Sandor Marton

Istvan Fekete

Affiliations

Soon will be listed here.

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.

Citing Articles

Demonstration of Group-Level and Individual-Level Efficacy Using Time-to-Event Designs for Clinical Trials of Antiseizure Medications.

Kerr W, Kok N, Reddy A, McFarlane K, Stern J, Pennell P Neurology. 2024; 103(4):e209713.

PMID: 39052963 PMC: 11271390. DOI: 10.1212/WNL.0000000000209713.

Prescribed antiseizure medication doses and their relation to defined daily doses for achieving seizure freedom in newly diagnosed patients with epilepsy.

Hersi H, Raitanen J, Saarinen J, Peltola J Epilepsia Open. 2023; 8(3):811-819.

PMID: 37010264 PMC: 10472398. DOI: 10.1002/epi4.12737.

Impact of epilepsy and its treatment on brain metastasis from solid tumors: A retrospective study.

Maschio M, Maialetti A, Giannarelli D, Koudriavtseva T, Galie E, Fabi A Front Neurol. 2022; 13:967946.

PMID: 36341097 PMC: 9634121. DOI: 10.3389/fneur.2022.967946.

Role of clinical pharmacists in epilepsy management at a general hospital in Vietnam: a before-and-after study.

Pham H, Tran M, Nguyen N, Tan Vo V, Tran M J Pharm Policy Pract. 2021; 14(1):109.

PMID: 34930487 PMC: 8686354. DOI: 10.1186/s40545-021-00394-9.

Comparison of Long-Term Outcomes of Monotherapy and Polytherapy in Seizure-Free Patients With Epilepsy Following Antiseizure Medication Withdrawal.

Wang Y, Xia L, Li R, Li Y, Li J, Zhou Q Front Neurol. 2021; 12:669703.

PMID: 34108931 PMC: 8182048. DOI: 10.3389/fneur.2021.669703.

References

Chadwick D . Epilepsy. J Neurol Neurosurg Psychiatry. 1994; 57(3):264-77. PMC: 1072813. DOI: 10.1136/jnnp.57.3.264. View

Koristkova B, Grundmann M, Brozmanova H . Differences between prescribed daily doses and defined daily doses of antiepileptics--therapeutic drug monitoring as a marker of the quality of the treatment. Int J Clin Pharmacol Ther. 2006; 44(9):438-42. DOI: 10.5414/cpp44438. View

French J, Pedley T . Clinical practice. Initial management of epilepsy. N Engl J Med. 2008; 359(2):166-76. DOI: 10.1056/NEJMcp0801738. View

Hsieh L, Huang C . Antiepileptic drug utilization in Taiwan: analysis of prescription using National Health Insurance database. Epilepsy Res. 2009; 84(1):21-7. DOI: 10.1016/j.eplepsyres.2008.11.018. View

Lammers M, Hekster Y, Keyser A, van Lier H, Meinardi H, Renier W . Neither dosage nor serum levels of antiepileptic drugs are predictive for efficacy and adverse effects. Pharm World Sci. 1995; 17(6):201-6. DOI: 10.1007/BF01870612. View

van den Brand M, Pouwels S, Samson M, van Staa T, Thio B, Cooper C . Use of anti-depressants and the risk of fracture of the hip or femur. Osteoporos Int. 2009; 20(10):1705-13. PMC: 2744781. DOI: 10.1007/s00198-009-0849-6. View

Grimmsmann T, Himmel W . Discrepancies between prescribed and defined daily doses: a matter of patients or drug classes?. Eur J Clin Pharmacol. 2011; 67(8):847-54. PMC: 3134712. DOI: 10.1007/s00228-011-1014-7. View

Koristkova B, Sjoqvist F, Grundmann M, Bergman U . The use of TDM data to assess the validity of defined daily doses of antiepileptics: a comparison between a Czech and Swedish University Hospital. Ther Drug Monit. 2006; 28(5):589-93. DOI: 10.1097/01.ftd.0000245383.79939.ed. View

Horvath L, Fekete K, Marton S, Fekete I . Outcome of antiepileptic drug treatment of 1282 patients with epilepsy, their pharmacovigilance reports and concomitant medication on CNS in an East-Hungarian adult database. J Neurol Sci. 2016; 369:220-226. DOI: 10.1016/j.jns.2016.08.039. View

10.

Rochat P, Hallas J, Gaist D, Friis M . Antiepileptic drug utilization: a Danish prescription database analysis. Acta Neurol Scand. 2001; 104(1):6-11. DOI: 10.1034/j.1600-0404.2001.00197.x. View

11.

Khong T, de Vries F, Goldenberg J, Klungel O, Robinson N, Ibanez L . Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the United States. Calcif Tissue Int. 2012; 91(1):24-31. PMC: 3382650. DOI: 10.1007/s00223-012-9603-8. View

12.

Lammers M, Hekster Y, Keyser A, Meinardi H, Renier W, Herings R . Use of antiepileptic drugs in a community-dwelling Dutch population. Neurology. 1996; 46(1):62-7. DOI: 10.1212/wnl.46.1.62. View

13.

Brodie M, Kwan P . Staged approach to epilepsy management. Neurology. 2002; 58(8 Suppl 5):S2-8. DOI: 10.1212/wnl.58.8_suppl_5.s2. View

14.

Kwan P, Brodie M . Combination therapy in epilepsy: when and what to use. Drugs. 2006; 66(14):1817-29. DOI: 10.2165/00003495-200666140-00004. View

15.

Monnet D, Molstad S, Cars O . Defined daily doses of antimicrobials reflect antimicrobial prescriptions in ambulatory care. J Antimicrob Chemother. 2004; 53(6):1109-11. DOI: 10.1093/jac/dkh230. View

16.

Muller A, Monnet D, Talon D, Henon T, Bertrand X . Discrepancies between prescribed daily doses and WHO defined daily doses of antibacterials at a university hospital. Br J Clin Pharmacol. 2006; 61(5):585-91. PMC: 1885049. DOI: 10.1111/j.1365-2125.2006.02605.x. View

17.

Kwan P, Brodie M . Definition of refractory epilepsy: defining the indefinable?. Lancet Neurol. 2009; 9(1):27-9. DOI: 10.1016/S1474-4422(09)70304-7. View

18.

Patsalos P, Berry D, Bourgeois B, Cloyd J, Glauser T, Johannessen S . Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008; 49(7):1239-76. DOI: 10.1111/j.1528-1167.2008.01561.x. View

19.

Kwan P, Arzimanoglou A, Berg A, Brodie M, Hauser W, Mathern G . Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2009; 51(6):1069-77. DOI: 10.1111/j.1528-1167.2009.02397.x. View

20.

Glauser T, Ben-Menachem E, Bourgeois B, Cnaan A, Chadwick D, Guerreiro C . ILAE treatment guidelines: evidence-based analysis of antiepileptic drug efficacy and effectiveness as initial monotherapy for epileptic seizures and syndromes. Epilepsia. 2006; 47(7):1094-120. DOI: 10.1111/j.1528-1167.2006.00585.x. View