Generic placeholder image

Current Clinical Pharmacology

Editor-in-Chief

ISSN (Print): 1574-8847
ISSN (Online): 2212-3938

Research Article

Investigation of the Roles of New Antiepileptic Drugs and Serum BDNF Levels in Efficacy and Safety Monitoring and Quality of Life: A Clinical Research

Author(s): Meral Demir*, Emel O. Akarsu, Hava O. Dede, Nerses Bebek, Sevda O. Yıldız, Betül Baykan and Ahmet G. Akkan

Volume 15, Issue 1, 2020

Page: [49 - 63] Pages: 15

DOI: 10.2174/1574884714666190312145409

Abstract

Objective: We aimed to determine the therapeutic drug monitoring (TDM) features and the relation to Brain-Derived Neurotrophic Factor (BDNF) of frequently used new antiepileptic drugs (NADs) including lamotrigine (LTG), oxcarbazepine (OXC), zonisamide (ZNS) and lacosamide (LCM). Moreover, we investigated their effect on the quality of life (QoL).

Methods: Eighty epileptic patients who had been using the NADs, and thirteen healthy participants were included in this cross-sectional study. The participants were randomized into groups. The QOLIE-31 test was used for the assessment of QoL. We also prepared and applied "Safety Test". HPLC method for TDM, and ELISA method for BDNF measurements were used consecutively.

Results: In comparison to healthy participants, epileptic participants had lower marriage rate (p=0.049), education level (p˂0.001), alcohol use (p=0.002). BDNF levels were higher in patients with focal epilepsy (p=0.013) and in those with higher education level (p=0.016). There were negative correlations between serum BDNF levels and serum ZNS levels (p=0.042) with LTGpolytherapy, serum MHD levels (a 10-monohydroxy derivative of OXC, p=0.041) with OXCmonotherapy. There was no difference in BDNF according to monotherapy-polytherapy, drugresistant groups, regarding seizure frequency. There was a positive correlation between total health status and QoL (p˂0.001). QOLIE-31 overall score (OS) was higher in those with OXCmonotherapy (76.5±14.5). OS (p˂0.001), seizure worry (SW, p=0.004), cognition (C, p˂0.001), social function (SF, p˂0.001) were different in the main groups. Forgetfulness was the most common unwanted effect.

Conclusion: While TDM helps the clinician to use more effective and safe NADs, BDNF may assist in TDM for reaching the therapeutic target in epilepsy.

Keywords: Epilepsy, new antiepileptic drugs, TDM, safety, QOLIE-31, BDNF, efficacy.

Graphical Abstract

[1]
Azuma H, Akechi T. Effects of psychosocial functioning, depression, seizure frequency, and employment on quality of life in patients with epilepsy. Epilepsy Behav 2014; 41: 18-20.
[http://dx.doi.org/10.1016/j.yebeh.2014.09.025] [PMID: 25269689]
[2]
Patsalos PN, Berry DJ, Bourgeois BF, et al. 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.
[http://dx.doi.org/10.1111/j.1528-1167.2008.01561.x] [PMID: 18397299]
[3]
Destache CJ. Use of therapeutic drug monitoring in pharmacoeconomics. Ther Drug Monit 1993; 15(6): 608-10.
[http://dx.doi.org/10.1097/00007691-199312000-00028] [PMID: 8122303]
[4]
Krasowski MD, McMillin GA. Advances in anti-epileptic drug testing. Clin Chim Acta 2014; 436: 224-36.
[http://dx.doi.org/10.1016/j.cca.2014.06.002] [PMID: 24925169]
[5]
Sener A, Akkan AG, Malaisse WJ. Standardized procedure for the assay and identification of hypoglycemic sulfonylureas in human plasma. Acta Diabetol 1995; 32(1): 64-8.
[http://dx.doi.org/10.1007/BF00581049] [PMID: 7612921]
[6]
Johannessen SI, Tomson T. Pharmacokinetic variability of newer antiepileptic drugs: when is monitoring needed? Clin Pharmacokinet 2006; 45(11): 1061-75.
[http://dx.doi.org/10.2165/00003088-200645110-00002] [PMID: 17048972]
[7]
Gökyiğit A, Baykan-Kurt B, Karaağaç N, et al. Tedaviye dirençli epilepside ek tedavi olarak uygulanan lamotrigin ile 3 aylık, çok merkezli, etkinlik ve güvenilirlik çalışması. Epilepsi 1997; 3: 21-6.
[8]
Pollard JR, Eidelman O, Mueller GP, et al. The TARC/sICAM5 ratio in patient plasma is a candidate biomarker for drug resistant epilepsy. Front Neurol 2013; 3(181): 181.
[http://dx.doi.org/10.3389/fneur.2012.00181] [PMID: 23293627]
[9]
Kalia M, Costa E Silva J, Silva J. Biomarkers of psychiatric diseases: current status and future prospects. Metabolism 2015; 64(3)(Suppl. 1): S11-5.
[http://dx.doi.org/10.1016/j.metabol.2014.10.026] [PMID: 25467847]
[10]
Russo-Neustadt AA, Chen MJ. Brain-derived neurotrophic factor and antidepressant activity. Curr Pharm Des 2005; 11(12): 1495-510.
[http://dx.doi.org/10.2174/1381612053764788] [PMID: 15892658]
[11]
Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov 2011; 10(3): 209-19.
[http://dx.doi.org/10.1038/nrd3366] [PMID: 21358740]
[12]
Hong Z, Li W, Qu B, et al. Serum brain-derived neurotrophic factor levels in epilepsy. Eur J Neurol 2014; 21(1): 57-64.
[http://dx.doi.org/10.1111/ene.12232] [PMID: 23879572]
[13]
Ventriglia M, Zanardini R, Bonomini C, et al. Serum brain-derived neurotrophic factor levels in different neurological diseases. BioMed Res Int 2013; 2013901082
[http://dx.doi.org/10.1155/2013/901082] [PMID: 24024214]
[14]
Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE commission on classification and terminology 2005-2009 Epilepsia 2010; 5: 676-85.
[15]
ClinRep therapeutic drug monitoring. HPLC complete kits (web page on the internet) Access, 25.2.2015. www.recipe.de/en/products_hplc.htlm
[16]
Vickrey BG, Perrine KR, Hays RD, et al. Quality of life in epilepsy QOLIE-31 Version 10 Scoring Manual (web page on the internet) Access, 13.3.2015. www.rand.org
[17]
Mollaoğlu M, Durna Z, Bolayir E. Validity and reliability of the quality of life in epilepsy inventory (QOLIE-31) for Turkey. Noro Psikiyatri Arsivi 2015; 52(3): 289-95.
[http://dx.doi.org/10.5152/npa.2015.8727] [PMID: 28360726]
[18]
Truven Health Analytics Micromedex Solutions Veritabanı (web page on the internet) Access, 18.2.2015. http: //www.micromedexsolutions. com/micromedex2/librarian/ (Accessed on 18 February 2015).
[19]
Shimizu E, Hashimoto K, Okamura N, et al. Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 2003; 54(1): 70-5.
[http://dx.doi.org/10.1016/S0006-3223(03)00181-1] [PMID: 12842310]
[20]
van Veenendaal TM, IJff DM, Aldenkamp AP, et al. Chronic antiepileptic drug use and functional network efficiency: A functional magnetic resonance imaging study. World J Radiol 2017; 9(6): 287-94.
[http://dx.doi.org/10.4329/wjr.v9.i6.287] [PMID: 28717415]
[21]
Bennewitz MF, Saltzman WM. Nanotechnology for delivery of drugs to the brain for epilepsy. Neurotherapeutics 2009; 6(2): 323-36.
[http://dx.doi.org/10.1016/j.nurt.2009.01.018] [PMID: 19332327]
[22]
Faught E, Szaflarski JP, Richman J, et al. Risk of pharmacokinetic interactions between antiepileptic and other drugs in older persons and factors associated with risk. Epilepsia 2018; 59(3): 715-23.
[http://dx.doi.org/10.1111/epi.14010] [PMID: 29411348]
[23]
Turkish Medicines and Medical Devices Agency Short Product Information (web page on the internet).. www.titck.gov.tr (Accessed on 18 February 2015).
[24]
Kayaalp O. Akılcı Tedavi yönünden Tıbbi Farmakoloji Kitabı 13nd. Ankara: Pelikan Yayıncılık 2012.
[25]
Marson AG, Kadir ZA, Hutton JL, Chadwick DW. The new antiepileptic drugs: a systematic review of their efficacy and tolerability. Epilepsia 1997; 38(8): 859-80.
[http://dx.doi.org/10.1111/j.1528-1157.1997.tb01251.x] [PMID: 9579887]
[26]
Gallelli L, Palleria C, De Vuono A, et al. Safety and efficacy of generic drugs with respect to brand formulation. J Pharmacol Pharmacother 2013; 4(Suppl. 1): S110-4.
[http://dx.doi.org/10.4103/0976-500X.120972] [PMID: 24347975]
[27]
Rosenow F, van Alphen N, Becker A, et al. Personalized translational epilepsy research - Novel approaches and future perspectives: Part I: Clinical and network analysis approaches. Epilepsy Behav 2017; 76: 13-8.
[http://dx.doi.org/10.1016/j.yebeh.2017.06.041] [PMID: 28917501]
[28]
de Almeida AA, Gomes da Silva S, Lopim GM, et al. Resistance exercise reduces seizure occurrence, attenuates memory deficits and restores BDNF signaling in rats with chronic epilepsy. Neurochem Res 2017; 42(4): 1230-9.
[http://dx.doi.org/10.1007/s11064-016-2165-9] [PMID: 28078614]
[29]
Rouvel-Tallec A. [New antiepileptic drugs]. Rev Med Interne 2009; 30(4): 335-9.
[http://dx.doi.org/10.1016/j.revmed.2008.11.009] [PMID: 19195742]
[30]
LaFrance WC Jr, Leaver K, Stopa EG, Papandonatos GD, Blum AS. Decreased serum BDNF levels in patients with epileptic and psychogenic nonepileptic seizures. Neurology 2010; 75(14): 1285-91.
[http://dx.doi.org/10.1212/WNL.0b013e3181f612bb] [PMID: 20921514]
[31]
Abelaira HM, Réus GZ, Ribeiro KF, et al. Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats. Neurochem Int 2011; 59(8): 1163-74.
[http://dx.doi.org/10.1016/j.neuint.2011.10.007] [PMID: 22044672]
[32]
Arıcıoğlu F. Psikiyatride farmakorezistans. Klinik Psikofarmakol Bülteni 2009; 19(Suppl. 11): S43-53.
[33]
Kırlı S. Antidepresanların etki düzeneklerindeki benzerlik ve farklılıklar. Klinik Psikofarmakol Bülteni 2009; 19(Suppl. 1): S86-9.
[34]
Toth M. The epsilon theory: a novel synthesis of the underlying molecular and electrophysiological mechanisms of primary generalized epilepsy and the possible mechanism of action of valproate. Med Hypotheses 2005; 64(2): 267-72.
[http://dx.doi.org/10.1016/j.mehy.2004.07.019] [PMID: 15607553]
[35]
Kagawa S, Mihara K, Suzuki T, et al. Both serum brain-derived neurotrophic factor and interleukin-6 levels are not associated with therapeutic response to lamotrigine augmentation therapy in treatment-resistant depressive Disorder. Neuropsychobiology 2017; 75(3): 145-50.
[http://dx.doi.org/10.1159/000484665] [PMID: 29332095]
[36]
Smith RL, Haslemo T, Refsum H, Molden E. Impact of age, gender and CYP2C9/2C19 genotypes on dose-adjusted steady-state serum concentrations of valproic acid-a large-scale study based on naturalistic therapeutic drug monitoring data. Eur J Clin Pharmacol 2016; 72(9): 1099-104.
[http://dx.doi.org/10.1007/s00228-016-2087-0] [PMID: 27353638]
[37]
Genton P. When antiepileptic drugs aggravate epilepsy. Brain Dev 2000; 22(2): 75-80.
[http://dx.doi.org/10.1016/S0387-7604(99)00113-8] [PMID: 10722956]
[38]
Moon HJ, Jeon B. Can therapeutic-range chronic phenytoin administration cause cerebellar ataxia? J Epilepsy Res 2017; 7(1): 21-4.
[http://dx.doi.org/10.14581/jer.17004] [PMID: 28775951]
[39]
Chen NC, Chuang YC, Huang CW, et al. Interictal serum brain-derived neurotrophic factor level reflects white matter integrity, epilepsy severity, and cognitive dysfunction in chronic temporal lobe epilepsy. Epilepsy Behav 2016; 59: 147-54.
[http://dx.doi.org/10.1016/j.yebeh.2016.02.029] [PMID: 27152461]
[40]
Glien M, Brandt C, Potschka H, Löscher W. Effects of the novel antiepileptic drug levetiracetam on spontaneous recurrent seizures in the rat pilocarpine model of temporal lobe epilepsy. Epilepsia 2002; 43(4): 350-7.
[http://dx.doi.org/10.1046/j.1528-1157.2002.18101.x] [PMID: 11952764]
[41]
van Dijkman SC, Rauwé WM, Danhof M, Della Pasqua O. Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children. Br J Clin Pharmacol 2018; 84(1): 97-111.
[http://dx.doi.org/10.1111/bcp.13400] [PMID: 28815754]
[42]
Johannessen SI, Landmark CJ. Antiepileptic drug interactions - principles and clinical implications. Curr Neuropharmacol 2010; 8(3): 254-67.
[http://dx.doi.org/10.2174/157015910792246254] [PMID: 21358975]
[43]
French JA, Gazzola DM. New generation antiepileptic drugs: what do they offer in terms of improved tolerability and safety? Ther Adv Drug Saf 2011; 2(4): 141-58.
[http://dx.doi.org/10.1177/2042098611411127] [PMID: 25083209]
[44]
Egunsola O, Choonara I, Sammons HM, Whitehouse WP. Safety of antiepileptic drugs in children and young people: A prospective cohort study. Seizure 2018; 56: 20-5.
[http://dx.doi.org/10.1016/j.seizure.2018.01.018] [PMID: 29427834]
[45]
Endesfelder S, Weichelt U, Schiller C, Winter K, von Haefen C, Bührer C. Caffeine protects against anticonvulsant-induced impaired neurogenesis in the developing rat brain. Neurotox Res 2018; 34(2): 173-87.
[http://dx.doi.org/10.1007/s12640-018-9872-8] [PMID: 29417440]
[46]
Shi XY, Wang JW, Cui H, Li BM, Lei GF, Sun RP. Effects of antiepileptic drugs on mRNA levels of BDNF and NT-3 and cell neogenesis in the developing rat brain. Brain Dev 2010; 32(3): 229-35.
[http://dx.doi.org/10.1016/j.braindev.2009.03.012] [PMID: 19394173]
[47]
Shishmanova-Doseva M, Peychev L, Koeva Y, Terzieva D, Georgieva K, Peychev Z. Chronic treatment with the new anticonvulsant drug lacosamide impairs learning and memory processes in rats: A possible role of BDNF/TrkB ligand receptor system. Pharmacol Biochem Behav 2018; 169: 1-9.
[http://dx.doi.org/10.1016/j.pbb.2018.03.009] [PMID: 29605232]
[48]
Javed A, Cohen B, Detyniecki K, et al. Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up. Seizure 2015; 29: 34-40.
[http://dx.doi.org/10.1016/j.seizure.2015.03.013] [PMID: 26076842]
[49]
Burnouf T, Kuo YP, Blum D, Burnouf S, Su CY. Human platelet concentrates: a source of solvent/detergent-treated highly enriched brain-derived neurotrophic factor. Transfusion 2012; 52(8): 1721-8.
[http://dx.doi.org/10.1111/j.1537-2995.2011.03494.x] [PMID: 22211513]
[50]
Haag A, Strzelczyk A, Bauer S, Kühne S, Hamer HM, Rosenow F. Quality of life and employment status are correlated with antiepileptic monotherapy versus polytherapy and not with use of “newer” versus “classic” drugs: results of the “Compliant 2006” survey in 907 patients. Epilepsy Behav 2010; 19(4): 618-22.
[http://dx.doi.org/10.1016/j.yebeh.2010.09.037] [PMID: 21115406]
[51]
Glauser TA, Pippenger CE. Controversies in blood-level monitoring: reexamining its role in the treatment of epilepsy. Epilepsia 2000; 41(Suppl. 8): S6-S15.
[http://dx.doi.org/10.1111/j.1528-1157.2000.tb02950.x] [PMID: 11092608]

© 2024 Bentham Science Publishers | Privacy Policy