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  1. The use of lamotrigine and other antiepileptic drugs in paediatric patients at a Malaysian hospital
    Ab Rahman AF, Ibrahim MI, Ismail HI, Seng TB
    Pharm World Sci, 2005 Oct;27(5):403-6.
    PMID: 16341748
    OBJECTIVE: (1) To determine the effect of lamotrigine add-on therapy on the seizure frequency and cost in paediatric patients. (2) To determine the prescribing pattern of other antiepileptic drugs (AEDs).

    METHOD: A retrospective study of medical records was carried out from October 2000 to June 2001 at the paediatric clinic, Hospital Pulau Pinang.

    MAIN OUTCOME MEASURE: Seizure frequency, cost of drug and types of AED prescribed.

    RESULTS: A total of 209 medical records were retrieved during the study period. Lamotrigine (LTG) was prescribed in 29 patients as add-on therapy. In 18 patients, there was a significant reduction in seizure frequency after the addition of LTG. Approximately 70% experienced a reduction in seizure frequency of more than 50%. Side effects of LTG were considered mild and manageable. However, drug cost after the addition of LTG increased by 103%. In the remaining 180 patients, the most common AED prescribed was sodium valproate (VPA). Only 15% of the patients received combination therapy. Mean monthly cost of monotherapy was found to be RM 24.4 while monthly cost of combination therapy was RM 45.4 (1 Euro-RM 5.00).

    CONCLUSION: The majority of paediatric patients in the study are on AED monotherapy and only a small percentage was prescribed lamotrigine. The use of lamotrigine is associated with better seizure control but with an increase in drug cost.

    Study site: paediatric clinic, Hospital Pulau Pinang.
    Matched MeSH terms: Anticonvulsants/therapeutic use*
  2. A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts
    Amini E, Rezaei M, Mohamed Ibrahim N, Golpich M, Ghasemi R, Mohamed Z, et al.
    Mol Neurobiol, 2015 Aug;52(1):492-513.
    PMID: 25195699 DOI: 10.1007/s12035-014-8876-5
    Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  3. Tumor Necrosis Factor-α, the Pathological Key to Post-Traumatic Epilepsy: A Comprehensive Systematic Review
    Arulsamy A, Shaikh MF
    ACS Chem Neurosci, 2020 07 01;11(13):1900-1908.
    PMID: 32479057 DOI: 10.1021/acschemneuro.0c00301
    Post-traumatic epilepsy (PTE) is one of the detrimental outcomes of traumatic brain injury (TBI), resulting in recurrent seizures that impact daily life. However, the pathological relationship between PTE and TBI remains unclear, and commonly prescribed antiepileptic drugs (AED) are ineffective against PTE. Fortunately, emerging research implicates neuroinflammation, particularly, tumor necrosis factor-α (TNF-α), as the key mediator for PTE development. Thus, this review aims to examine the available literature regarding the role of TNF-α in PTE pathology and, subsequently, evaluate TNF-α as a possible target for its treatment. A comprehensive literature search was conducted on four databases including PubMed, CINAHL, Embase, and Scopus. Articles with relevance in investigating TNF-α expression in PTE were considered in this review. Critical evaluation of four articles that met the inclusion criteria suggests a proportional relationship between TNF-α expression and seizure susceptibilit and that neutralization or suppression of TNF-α release results in reduced susceptibility to seizures. In conclusion, this review elucidates the importance of TNF-α expression in epileptogenesis postinjury and urges future research to focus more on clinical studies involving TNF-α, which may provide clearer insight into PTE prevention, therefore improving the lives of PTE patients.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  4. Fulltext Protective effect of α-asarone against nicotine-induced seizures in mice, but not by its interaction with nicotinic acetylcholine receptors
    Chellian R, Pandy V
    Biomed Pharmacother, 2018 Dec;108:1591-1595.
    PMID: 30372861 DOI: 10.1016/j.biopha.2018.09.137
    Alpha-asarone is one of the bioactive phytochemicals present in the rhizomes of Acorus species and demonstrated its anticonvulsant activity in rodents. Alpha-asarone protected mice from the gamma-aminobutyric acid (GABA) type A receptor antagonist or N-methyl-d-aspartate (NMDA) receptor agonist-induced seizures. In our recent study, α-asarone attenuated the nicotine withdrawal-induced depression-like behavior in mice. The seizures induced by nicotine is mediated through the activation of nicotinic acetylcholine receptors (nAChRs) and stimulation of NMDA receptors. Therefore, we hypothesized that α-asarone might be effective against nicotine-induced seizures. Also, the interaction of α-asarone with nAChRs is unknown. In this study, we investigated the effect of α-asarone on the locomotor activity and body temperature in mice. In addition, we studied the effect of α-asarone on nicotine-induced seizures in mice. Finally, we assessed in vivo pharmacodynamic interaction of α-asarone with nAChRs using nicotine-induced hypomotility and hypothermia tests in mice. The results of this study showed that the α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) treatment significantly decreased the locomotor activity and body temperature in mice. Furthermore, α-asarone (50-200 mg/kg, i.p.) and diazepam (5 mg/kg, i.p.) pretreatment significantly prolonged the onset time of nicotine-induced seizures in mice. However, α-asarone (30 and 50 mg/kg, i.p.) pretreatment did not inhibit the nicotine-induced hypomotility or hypothermia in mice. Conversely, mecamylamine (1 mg/kg, s.c.) pretreatment completely blocked the nicotine-induced seizures and significantly prevents the nicotine-induced hypomotility and hypothermia in mice. Overall, these results suggest that the protective effect of α-asarone against nicotine-induced seizures did not mediate through the antagonism of nAChRs. We also postulated that the GABAergic and glutamatergic activities of α-asarone could be involved in its protective effect against nicotine-induced seizures and based on this aspect further studies are required.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  5. Fulltext Clinical use of mood stabilizers beyond treatment for bipolar disorder: The REAP-MS study
    Chen CK, Yang SY, Park SC, Jang OJ, Zhu X, Xiang YT, et al.
    Asian J Psychiatr, 2023 Jul;85:103613.
    PMID: 37163943 DOI: 10.1016/j.ajp.2023.103613
    OBJECTIVE: Mood stabilizers are psychotropic drugs mainly used to treat bipolar disorder in the acute phase or for maintenance therapy to prevent relapse. In clinical practice, mood stabilizers are commonly prescribed for conditions other than bipolar disorder. This study investigated the distribution of mood stabilizer prescriptions for different psychiatric diagnoses and studied differences in the drugs, dosage, and plasma concentration in 10 Asian countries including Taiwan, South Korea, Malaysia, China, Thailand, India, Pakistan, Singapore, Indonesia, and Myanmar.

    METHODS: Patients prescribed mood stabilizers (lithium, carbamazepine, valproic acid, or lamotrigine) for a psychiatric condition other than bipolar disorder (codes F31.0-F31.9 in the International Classification of Diseases, 10th Edition, Clinical Modification) were recruited through convenience sampling. A website-based data entry system was used for data collection.

    RESULTS: In total, 1557 psychiatric patients were enrolled. Schizophrenia, schizotypal, delusional, and other non-mood psychotic disorders (F20-F29, 55.8 %) was the most common diagnosis, followed by non-bipolar mood disorders (F30, F31- F39, 25.3 %), organic mental disorder (F00-F09, 8.8 %), mental retardation (F70-F79, 5.8 %) and anxiety, dissociative, stress-related, somatoform and other nonpsychotic mental disorders (F40-F48, 4.4 %). The most frequently targeted symptoms (>20 %) were irritability (48 %), impulsivity (32.4 %), aggression (29.2 %), anger (20.8 %), and psychosis (24.1 %). Valproic acid was the most frequently used medication.

    CONCLUSIONS: Clinicians typically prescribe mood stabilizers as empirically supported treatment to manage mood symptoms in patients with diagnoses other than bipolar disorders, though there is on official indication for these disorders. The costs and benefits of this add-on symptomatic treatment warrant further investigation.

    Matched MeSH terms: Anticonvulsants/therapeutic use
  6. Idiopathic paroxysmal kinesigenic choreoathetosis: precipitation of attacks by vestibular stimulation
    Chew NK, Tan CT, Goh KJ
    J Clin Neurosci, 2002 Sep;9(5):604-5.
    PMID: 12383430
    A 24-year-old woman presented with a 3.5-year history of paroxysmal dystonia that was precipitated by sudden movement, especially when she started to walk. It was characterised by shrugging of shoulders, flexion of the neck and thoracic spine, and stiffness of the right leg followed by falls. Each attack lasted for less than 5min. Inadequate sleep and stress were exacerbating factors. There was no similar family history. Physical examination and investigations were normal. The following manoeuvres that caused vestibular stimulation precipitated attacks: turning her head from side to side while standing still, sitting still on a rotating chair and an ice-water caloric test. She had partial responses to phenytoin and levodopa, and a good response to haloperidol. Vestibular stimulation as a precipitating factor in paroxysmal kinesigenic choreoathetosis has not been reported previously.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  7. Fulltext Impact of complementary and alternative medicines on antiepileptic medication adherence among epilepsy patients
    Farrukh MJ, Makmor-Bakry M, Hatah E, Jan TH
    BMC Complement Med Ther, 2021 Feb 04;21(1):50.
    PMID: 33541336 DOI: 10.1186/s12906-021-03224-2
    BACKGROUND: The aim of this study was to assess the knowledge, attitude, and practice of complementary and alternative medicine (CAM) and its impact on antiepileptic drug (AED) adherence among patients with epilepsy.

    METHODS: A cross-sectional study was carried out on 100 epilepsy patients, aged 18 years or older that did not have any physical or psychiatric illness. A patient-administered questionnaire was used to assess their knowledge, attitude towards, practice, and perceived effectiveness (KAPP) of CAM. Established adherence assessment tools were used to determine patient medication adherence.

    RESULTS: The prevalence of CAM usage was found to be at 58%. CAM was used more frequently by males (n = 32, 60.4%) than by females (n = 26, 55.3%; p = 0.609). The most commonly used CAM included vitamins and minerals (36%), ginseng (16%), antioxidants (15%), and acupuncture (12%). A significant number of patients had low knowledge of (59%) and a positive attitude (54%) toward complementary and alternative medicine. Main reasons for using CAM were a lower price, better availability, and inadequate seizure control by AEDs. About 43% of the patients who used CAM informed their doctor. Prevalence of non-adherence to AED therapy was found to be 68%. A significant association was found between non-adherence and CAM usage (p 

    Matched MeSH terms: Anticonvulsants/therapeutic use*
  8. Determinants of low bone mineral density in children with epilepsy
    Fong CY, Kong AN, Noordin M, Poh BK, Ong LC, Ng CC
    Eur. J. Paediatr. Neurol., 2018 Jan;22(1):155-163.
    PMID: 29122496 DOI: 10.1016/j.ejpn.2017.10.007
    INTRODUCTION: Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy.

    METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.

    RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.

    Matched MeSH terms: Anticonvulsants/therapeutic use
  9. Fulltext Seizure induced by tranexamic acid in a patient with chronic kidney disease on maintenance dialysis
    Fuah KW, Lim CTS, Pang DCL, Wong JS
    Saudi J Kidney Dis Transpl, 2018 2 20;29(1):207-209.
    PMID: 29456232 DOI: 10.4103/1319-2442.225177
    Tranexamic acid (TXA) is an antifibrinolytic agent commonly used to achieve hemostasis. However, there have been a few case reports suggesting that high-dose intravenous TXA has epileptogenic property. In patients with renal impairment, even administering the usual recommended dose of TXA can induce seizure episodes. We present here a patient on hemodialysis who developed seizures after receiving two doses of TXA over 5 h period.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  10. Fulltext Lack of association of ABCB1 haplotypes on five loci with response to treatment in epilepsy
    Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.
    Seizure, 2011 Sep;20(7):546-53.
    PMID: 21530324 DOI: 10.1016/j.seizure.2011.04.003
    Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs3789243T allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C>T, C1236T, G2677T/A, rs6949448 C>T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  11. Association between ABCB1 polymorphism and response to sodium valproate treatment in Malaysian epilepsy patients
    Haerian BS, Lim KS, Tan HJ, Mohamed EH, Tan CT, Raymond AA, et al.
    Epileptic Disord, 2011 Mar;13(1):65-75.
    PMID: 21388909 DOI: 10.1684/epd.2011.0419
    Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypes were assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.
    Matched MeSH terms: Anticonvulsants/therapeutic use*
  12. Association of ABCB1 gene polymorphisms and their haplotypes with response to antiepileptic drugs: a systematic review and meta-analysis
    Haerian BS, Lim KS, Tan CT, Raymond AA, Mohamed Z
    Pharmacogenomics, 2011 May;12(5):713-25.
    PMID: 21391884 DOI: 10.2217/pgs.10.212
    Several studies demonstrated a link between ABCB1 gene variants and the response to treatment in epilepsy, but the results have been inconclusive. Here, we performed the first haplotype meta-analysis to examine the association of haplotypes of ABCB1 common variants with the response to treatment in epilepsy.
    Matched MeSH terms: Anticonvulsants/therapeutic use*
  13. Fulltext ABCB1 C3435T polymorphism and the risk of resistance to antiepileptic drugs in epilepsy: a systematic review and meta-analysis
    Haerian BS, Roslan H, Raymond AA, Tan CT, Lim KS, Zulkifli SZ, et al.
    Seizure, 2010 Jul;19(6):339-46.
    PMID: 20605481 DOI: 10.1016/j.seizure.2010.05.004
    The C3435T, a major allelic variant of the ABCB1 gene, is proposed to play a crucial role in drug-resistance in epilepsy. The C/C genotype carriers reportedly are at higher risk of pharmacoresistance to AEDs, but only in some studies. The hypothesis of the C-variant associated risk and resistance to antiepileptic drugs (AEDs) has been hampered by conflicting results from inadequate power in case-control studies. To assess the role of C3435T polymorphism in drug-resistance in epilepsy, a systematic review and meta-analysis was conducted.
    Matched MeSH terms: Anticonvulsants/therapeutic use*
  14. Fulltext Lack of association of ABCB1 and PXR polymorphisms with response to treatment in epilepsy
    Haerian BS, Lim KS, Mohamed EH, Tan HJ, Tan CT, Raymond AA, et al.
    Seizure, 2011 Jun;20(5):387-94.
    PMID: 21316268 DOI: 10.1016/j.seizure.2011.01.008
    It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  15. SCN1A, SCN2A and SCN3A gene polymorphisms and responsiveness to antiepileptic drugs: a multicenter cohort study and meta-analysis
    Haerian BS, Baum L, Kwan P, Tan HJ, Raymond AA, Mohamed Z
    Pharmacogenomics, 2013 Jul;14(10):1153-66.
    PMID: 23859570 DOI: 10.2217/pgs.13.104
    Aim: Approximately a third of newly diagnosed epilepsy patients do not respond to antiepileptic drugs (AEDs). Evidence suggests that low penetrance variants in the genes of drug targets such as voltage-gated sodium channels may be involved in drug responsiveness. To examine this hypothesis, we compared data from two epilepsy cohorts from Malaysia and Hong Kong, as well as a meta-analysis from published data.

    Materials & methods: Genotype analysis of 39 polymorphisms located in the SCN1A, SCN2A and SCN3A genes was performed on 1504 epilepsy patients from Malaysia and Hong Kong who were receiving AEDs. Meta-analysis was performed for pooled data of SCN1A rs3812718 and rs2298771, and SCN2A rs17183814 polymorphisms.

    Results: Our data from the Hong Kong and Malaysia cohorts showed no significant allele, genotype and haplotype association of polymorphisms in the SCN1A, SCN2A, and SCN3A genes with drug responsiveness in epilepsy. This finding was supported by a meta-analysis for SCN1A rs3812718 and rs2298771, and for SCN2A rs17183814 polymorphisms.

    Conclusion: Our comprehensive study suggests that common polymorphisms in SCN1A, SCN2A and SCN3A do not play major roles in influencing response to AEDs.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  16. Fulltext Antiepileptic drug utilisation and seizure outcome among paediatric patients in a Malaysian public hospital
    Hasan SS, Bahari MB, Babar ZU, Ganesan V
    Singapore Med J, 2010 Jan;51(1):21-7.
    PMID: 20200771
    INTRODUCTION: The primary purpose of this study was to evaluate the utilisation pattern and seizure outcome of newer and older antiepileptic drugs in paediatric clinical practice in a Malaysian hospital setting.
    METHODS: Over a two-month period, all paediatric epilepsy patients from Penang General Hospital, Malaysia who were diagnosed according to the classification of the International League Against Epilepsy were followed up prospectively, and the patients' information was gathered with the help of a validated data collection form. This included demographic characteristics, monotherapy and polytherapy of antiepileptic drugs, as well as the number of seizures experienced.
    RESULTS: Partial seizures, including complex and simple partial seizures (47.2 percent), followed by generalised seizures (40 percent), were the most common seizure types found in this study. An average of 1.51 antiepileptic drugs per patient was prescribed, with 54.3 percent of the patients on monotherapy and 45.7 percent on polytherapy. Overall, sodium valproate was the most frequently prescribed antiepileptic drug (36.8 percent), followed by carbamazepine (30.2 percent) and lamotrigine (10.4 percent). Carbamazepine was the most frequently prescribed monotherapy (28.6 percent), followed by sodium valproate (17.1 percent). The newer antiepileptic drugs were also found to be used as monotherapy in 7.2 percent of the cases. Moreover, a significant difference was observed between the older and newer antiepileptic drugs in terms of the number of seizures experienced (p=0.027). Most (75 percent) of the seizure-free patients were on carbamazepine monotherapy.
    CONCLUSION: Monotherapy was the most frequently used remedy in all forms of epilepsy. Overall, sodium valproate was the most commonly used drug, while carbamazepine was found to be more frequently used as monotherapy. There was a significant difference found between the older and newer antiepileptic drugs, with 87.5 percent of seizure-free patients on older antiepileptic drugs.

    Study site: all paediatric epilepsy patients from Penang General Hospital
    Matched MeSH terms: Anticonvulsants/therapeutic use*
  17. The complexity of achieving anticoagulation control in the face of warfarin-phenytoin interaction: an Asian case report
    Hassan Y, Awaisu A, Aziz NA, Ismail O
    Pharm World Sci, 2005 Feb;27(1):16-9.
    PMID: 15861930
    Phenytoin has been reported to have major interactions with warfarin. Phenytoin induces warfarin's metabolism. However, there are many case reports which provide conflicting conclusions. Here, we report a case of a 65-year-old man with mechanical heart valve on chronic warfarin therapy who experienced persistent fluctuations of INR and bleeding secondary to probable warfarin-phenytoin interactions. The patient's anticoagulation clinic visits prior to hospitalization were thoroughly evaluated and we continued to follow-up the case for 3 months post-hospitalization. The reported interaction could be reasonably explained from the chronology of events and the pattern of INR fluctuations whenever phenytoin was either added or discontinued from his drug regimen.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  18. Fulltext A post hoc analysis of the long-term safety and efficacy of perampanel in Asian patients with epilepsy
    Inoue Y, Kaneko S, Hsieh PF, Meshram C, Lee SA, Aziz ZA, et al.
    Epilepsia, 2019 03;60 Suppl 1:60-67.
    PMID: 30869167 DOI: 10.1111/epi.14645
    This post hoc analysis assessed the long-term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic-clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long-term extension phase of 3 phase-3 perampanel trials (study 307) or the 10-week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double-blind phase-3 trials and 669 had previously received perampanel 2-12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment-emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre-perampanel baseline for all focal seizures was -28.1%, and -51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre-perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long-term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase-3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.
    Matched MeSH terms: Anticonvulsants/therapeutic use*
  19. Possible interplay between the theories of pharmacoresistant epilepsy
    Juvale IIA, Che Has AT
    Eur J Neurosci, 2021 03;53(6):1998-2026.
    PMID: 33306252 DOI: 10.1111/ejn.15079
    Epilepsy is one of the oldest known neurological disorders and is characterized by recurrent seizure activity. It has a high incidence rate, affecting a broad demographic in both developed and developing countries. Comorbid conditions are frequent in patients with epilepsy and have detrimental effects on their quality of life. Current management options for epilepsy include the use of anti-epileptic drugs, surgery, or a ketogenic diet. However, more than 30% of patients diagnosed with epilepsy exhibit drug resistance to anti-epileptic drugs. Further, surgery and ketogenic diets do little to alleviate the symptoms of patients with pharmacoresistant epilepsy. Thus, there is an urgent need to understand the underlying mechanisms of pharmacoresistant epilepsy to design newer and more effective anti-epileptic drugs. Several theories of pharmacoresistant epilepsy have been suggested over the years, the most common being the gene variant hypothesis, network hypothesis, multidrug transporter hypothesis, and target hypothesis. In our review, we discuss the main theories of pharmacoresistant epilepsy and highlight a possible interconnection between their mechanisms that could lead to the development of novel therapies for pharmacoresistant epilepsy.
    Matched MeSH terms: Anticonvulsants/therapeutic use
  20. Potential anti-epileptic phytoconstituents: An updated review
    Kaur J, Famta P, Famta M, Mehta M, Satija S, Sharma N, et al.
    J Ethnopharmacol, 2021 Mar 25;268:113565.
    PMID: 33166627 DOI: 10.1016/j.jep.2020.113565
    ETHNOPHARMACOLOGICAL RELEVANCE: Epilepsy is one of the most commonly occurring non-communicable neurological disorder that affects people of all age groups. Around 50 million people globally are epileptic, with 80% cases in developing countries due to lack of access to treatments determined by high cost and poor availability or it can be defined by the fraction of active epileptic patients who are not appropriately being treated. The availability of antiepileptic drugs and their adjuvant therapy in such countries is less than 50% and these are highly susceptible to drug interactions and severe adverse effects. As a result, the use of herbal medicine is increasingly becoming popular.

    AIM OF THE STUDY: To provide pharmacological information on the active constituents evaluated in the preclinical study to treat epilepsy with potential to be used as an alternative therapeutic option in future. It also provides affirmation for the development of novel antiepileptic drugs derived from medicinal plants.

    MATERIALS AND METHODS: Relevant information on the antiepileptic potential of phytoconstituents in the preclinical study (in-vitro, in-vivo) is provided based on their effect on screening parameters. Besides, relevant information on pharmacology of phytoconstituents, the traditional use of their medicinal plants related to epilepsy and status of phytoconstituents in the clinical study were derived from online databases, including PubMed, Clinicaltrial. gov, The Plant List (TPL, www.theplantlist.org), Science Direct. Articles identified using preset searching syntax and inclusion criteria are presented.

    RESULTS: More than 70% of the phytoconstituents reviewed in this paper justified the traditional use of their medicinal plant related to epilepsy by primarily acting on the GABAergic system. Amongst the phytoconstituents, only cannabidiol and tetrahydrocannabinol have been explored for clinical application in epilepsy.

    CONCLUSION: The preclinical and clinical data of the phytoconstituents to treat epilepsy and its associated comorbidities provides evidence for the discovery and development of novel antiepileptic drugs from medicinal plants. In terms of efficacy and safety, further randomized and controlled clinical studies are required to understand the complete pharmacodynamic and pharmacokinetic picture of phytoconstituents. Also, specific botanical source evaluation is needed.

    Matched MeSH terms: Anticonvulsants/therapeutic use*
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