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Epilepsia Open Jun 2024Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We...
OBJECTIVE
Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add-on ASMs for the treatment of focal epilepsy using network meta-analysis.
METHODS
Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment-emergent adverse events (TEAEs) and individual TEAEs were assessed. "Gemtc" 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI).
RESULTS
Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00-5.70) and 100% for rufinamide (2.03; 95% CI: 0.54-11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56-323.9) and zonisamide (10.63; 95% CI: 1.37-261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7-0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94-1.1; SUCRA: 0.885067) for overall TEAE compared with other medications.
SIGNIFICANCE
All approved ASMs were effective as add-on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom.
PLAIN LANGUAGE SUMMARY
This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.
PubMed: 38888005
DOI: 10.1002/epi4.12997 -
International Journal of Molecular... May 2024Doublecortin, encoded by the gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the gene are the major...
Doublecortin, encoded by the gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the gene are the major causes of the "lissencephaly (LIS) spectrum", which comprehends a milder phenotype like Subcortical Band Heterotopia (SBH) in heterozygous female subjects. We performed targeted sequencing in three unrelated female cases with SBH. We identified three DCX-related variants: a novel missense (c.601A>G: p.Lys201Glu), a novel nonsense (c.210C>G: p.Tyr70*), and a previously identified nonsense (c.907C>T: p.Arg303*) variant. The novel c.601A>G: p.Lys201Glu variant shows a mother-daughter transmission pattern across four generations. The proband exhibits focal epilepsy and achieved seizure freedom with a combination of oxcarbazepine and levetiracetam. All other affected members have no history of epileptic seizures. Brain MRIs of the affected members shows predominant fronto-central SBH with mixed pachygyria on the overlying cortex. The two nonsense variants were identified in two unrelated probands with SBH, severe drug-resistant epilepsy and intellectual disability. These novel DCX variants further expand the genotypic-phenotypic correlations of lissencephaly spectrum disorders. Our documented phenotypic descriptions of three unrelated families provide valuable insights and stimulate further discussions on DCX-SBH cases.
Topics: Humans; Female; Doublecortin Protein; Doublecortin Domain Proteins; Microtubule-Associated Proteins; Classical Lissencephalies and Subcortical Band Heterotopias; Phenotype; Pedigree; Neuropeptides; Codon, Nonsense; Adult; Mutation, Missense; Child; Magnetic Resonance Imaging; Child, Preschool; Adolescent
PubMed: 38791543
DOI: 10.3390/ijms25105505 -
Progress in Neuro-psychopharmacology &... Jul 2024Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Increasing evidence suggests that the physiological changes of pregnancy may impact pharmacokinetics of antiseizure medications (ASM), and this may affect treatment outcomes. The aim of this study was to quantify the pregnancy impact on the ASM pharmacokinetics.
METHODS
A systematic literature search was conducted in PubMed/EMBASE in November 2022 and updated in August 2023 for studies comparing levels of ASM in the same individuals during pregnancy and in the preconception/postpartum period. Alteration ratios between the 3rd trimester and baseline were estimated. We also performed a random-effects meta-analysis calculating between-timepoint differences in mean differences (MDs) and 95% confidence intervals (95%CIs) for dose-adjusted plasma concentrations (C/D ratios). Study quality was assessed using the ClinPK guidelines.
RESULTS
A total of 65 studies investigating 15 ASMs in 674 pregnancies were included. The largest differences were reported for lamotrigine, oxcarbazepine and levetiracetam (alteration ratio 0.42, range 0.07-2.45, 0.42, range 0.08-0.82 and 0.52, range 0.04-2.77 respectively): accordingly, C/D levels were lower in the 3rd trimester for lamotrigine, levetiracetam and the main oxcarbazepine metabolite monohydroxycarbazepine (MD = -12.33 × 10, 95%CI = -16.08 to -8.58 × 10 (μg/mL)/(mg/day), p < 0.001, MD = -7.16 (μg/mL)/(mg/day), 95%CI = -9.96 to -4.36, p < 0.001, and MD = -4.87 (μg/mL)/(mg/day), 95%CI = -9.39 to -0.35, p = 0.035, respectively), but not for oxcarbazepine (MD = 1.16 × 10 (μg/mL)/(mg/day), 95%CI = -2.55 to 0.24 × 10, p = 0.10). The quality of studies was acceptable with an average rating score of 11.5.
CONCLUSIONS
Data for lamotrigine, oxcarbazepine (and monohydroxycarbazepine) and levetiracetam demonstrate major changes in pharmacokinetics during pregnancy, suggesting the importance of therapeutic drug monitoring to assist clinicians in optimizing treatment outcomes.
Topics: Humans; Pregnancy; Anticonvulsants; Female; Pregnancy Complications; Levetiracetam; Lamotrigine; Epilepsy; Oxcarbazepine
PubMed: 38762161
DOI: 10.1016/j.pnpbp.2024.111030 -
Cureus Apr 2024Focal seizures with subjective auditory phenomena, known as auditory seizures, are uncommon and can include simple to complex auditory hallucinations. We present a case...
Focal seizures with subjective auditory phenomena, known as auditory seizures, are uncommon and can include simple to complex auditory hallucinations. We present a case of a 59-year-old man who presented with motor and non-motor seizures. He had a four-month history of hearing things resembling continuous metallic sounds, pennies dropping into a bank, persistent music after radio cessation, and the sound of a passing train. Brain MRI showed multiple serpiginous flow voids in the right temporal lobes, consistent with an arteriovenous malformation that was confirmed eventually with a diagnostic brain angiogram. The etiology of the seizures was related to a structural lesion in the setting of a right temporal arteriovenous malformation (AVM). Treatment with 2000mg of levetiracetam twice daily and 300mg of oxcarbazepine twice daily improved symptoms, and subsequent stereotactic radiosurgery ablation successfully treated the AVM. Post-treatment MRI showed reduced visibility of parasitized vessels, with controlled generalized seizures but partial control of auditory seizures.
PubMed: 38738099
DOI: 10.7759/cureus.57932 -
International Journal of General... 2024Levetiracetam (LEV) is commonly prescribed for epilepsy management. However, neuropsychiatric disorders (NPDs) are concerning adverse effects that may result in...
BACKGROUND
Levetiracetam (LEV) is commonly prescribed for epilepsy management. However, neuropsychiatric disorders (NPDs) are concerning adverse effects that may result in medication discontinuation. This study aims to examine the incidence and factors influencing LEV associated NPDs in adult patients aged 50 years and above.
METHODS
A retrospective analysis was conducted on patients aged 50 years and above prescribed LEV between 2010 and 2020, with at least one follow-up appointment six months post-treatment initiation. The incidence of new-onset or aggravated NPDs and variables potentially influencing this risk were examined. Independent -test, chi-squared, and Fisher's exact test were used, in addition to univariate and multivariate logistic regression.
RESULTS
The study included 100 patients with a mean age at LEV start of 63.31 years (SD = 16.48). Neuropsychiatric symptoms were observed in 6 (6.0%) patients. Factors associated with new-onset NPDs were younger age at epilepsy diagnosis (p=0.005), younger age at LEV start (p=0.004), and concurrent use of Carbamazepine/Oxcarbazepine (p=0.004). On multivariate analysis, only the association with Carbamazepine/Oxcarbazepine remained significant (OR 14.62, 95% CI 1.86-114.70, p=0.011).
CONCLUSION
The findings indicate that the incidence of NPDs in elderly patients is relatively low (6%). Further research with larger samples is needed in comparison with a younger sample as a control group to confirm these findings.
PubMed: 38736674
DOI: 10.2147/IJGM.S458803 -
Frontiers in Pediatrics 2024Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however,...
BACKGROUND
Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however, no consensus exists on applying LEV monotherapy among children with epilepsy.
OBJECTIVE
The present work focused on comparing the efficacy and safety of LEV and OXC monotherapy in treating children with epilepsy.
METHODS
We conducted a comprehensive search across multiple databases including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, VIP, and China Biology Medicine disc, covering studies from inception to August 26, 2023. We included randomized controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of LEV and OXC monotherapy for treating epilepsy in children. We utilized Cochrane Risk of Bias Tool in RevMan 5.3 software for assessing included RCTs quality. In addition, included cohort studies quality was determined using Newcastle-Ottawa Scale (NOS). A random-effects model was utilized to summarize the results.
RESULTS
This meta-analysis included altogether 14 studies, including 893 children with epilepsy. LEV and OXC monotherapy was not statistical different among children with epilepsy in seizure-free rate (relative risk [RR] = 1.010, 95% confidence interval [CI] [0.822, 1.242], > 0.05) and seizure frequency decrease of ≥50% compared with baseline [RR = 0.938, 95% CI (0.676, 1.301), > 0.05]. Differences in total adverse reaction rate [RR = 1.113, 95% CI (0.710, 1.744), > 0.05] and failure rate because of serious adverse reaction [RR = 1.001, 95% CI (0.349, 2.871), > 0.05] were not statistical different between LEV and OXC treatments among children with epilepsy. However, the effects of OXC monotherapy on thyroid among children with epilepsy was statistically correlated than that of LEV (thyroid stimulating hormone: standardized mean difference [SMD] = -0.144, 95% CI [-0.613, 0.325], > 0.05; free thyroxine: SMD = 1.663, 95% CI [0.179, 3.147], < 0.05).
CONCLUSION
The efficacy of LEV and OXC monotherapy in treating children with epilepsy is similar. However, OXC having a more significant effect on the thyroid than that of LEV. Therefore, LEV may be safer for children with epilepsy who are predisposed to thyroid disease than OXC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42024514016).
PubMed: 38711491
DOI: 10.3389/fped.2024.1336744 -
Cureus Apr 2024Hyponatremia is an adverse effect of many antiseizure medications (ASMs). It occurs with interference with the normal balance of electrolytes within the body. Various... (Review)
Review
Hyponatremia is an adverse effect of many antiseizure medications (ASMs). It occurs with interference with the normal balance of electrolytes within the body. Various risk factors associated with the development of hyponatremia in patients taking these medications include age, gender, dosage, and combinations with other drugs. ASMs such as carbamazepine (CBZ), oxcarbazepine (OXC), and valproic acid have a higher risk of hyponatremia. Hyponatremia induced by an antiseizure medication can occur through various mechanisms depending on the drug's specific mechanism of action. Hyponatremia can be a potentially fatal side effect. Patients taking these medications need to be monitored closely for the signs and symptoms of hyponatremia. Acute hyponatremia, defined as developing in <48 hours, is more likely to show symptoms than chronic hyponatremia. Signs of acute hyponatremia include delirium, seizures, decerebrate posturing, and cerebral edema with uncal herniation. Chronic hyponatremia, defined as developing in >48 hours, can cause lethargy, dizziness, weakness, headache, nausea, and confusion. Hyponatremia is associated with longer hospital stays and increased mortality. Treatment varies based on the degree of severity of hyponatremia. Choosing a treatment option should include consideration of the drug causing the electrolyte disturbance, the patient's risk factor profile, and the severity of symptoms as they present in the individual patient. Healthcare providers should be aware of hyponatremia as a potential side effect of ASMs, the signs and symptoms of hyponatremia, the different treatment options available, and the potential complications associated with rapid correction of hyponatremia.
PubMed: 38707045
DOI: 10.7759/cureus.57535 -
American Journal of Translational... 2024To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy.
OBJECTIVE
To explore the effect of levetiracetam combined with oxcarbazepine on the memory and cognitive function of adult patients with temporal lobe epilepsy.
METHODS
This retrospective analysis included 91 adult patients with temporal lobe epilepsy treated at Xianyang Hospital from June 2020 to December 2022. Based on their medication regimen, patients were categorized into an observation group (n=51) receiving levetiracetam plus oxcarbazepine and a control group (n=40) receiving only levetiracetam. Both groups underwent 3 months of continuous treatment. Therapeutic efficacy, pre- and post-treatment memory function (assessed using the Clinical Memory Scale, CMS), cognitive function (evaluated with the Wechsler Adult Intelligence Scale-Revised in China, WAISRC), anxiety and depression levels (measured by the Hamilton Anxiety Scale, HAMA, and Hamilton Depression Scale, HAMD), as well as adverse reactions, were compared between the two groups. Independent factors influencing treatment efficacy were also analyzed.
RESULTS
CMS and WAISRC scores significantly increased in both groups after treatment (both P=0.001), with the observation group showing more significant improvements than the control group (P=0.001). The improvements in HAMA and HAMD scores in the observation group were significantly better than the control group (all P<0.001). Adverse reaction occurrence showed no significant difference between the two groups (P>0.05). Prognostic analysis identified seizure frequency and treatment regimen as independent factors influencing efficacy.
CONCLUSION
Levetiracetam combined with oxcarbazepine effectively improves cognitive dysfunction in adults with temporal lobe epilepsy, with superior efficacy to levetiracetam alone, and good safety.
PubMed: 38586112
DOI: 10.62347/KNTE8578 -
Clinical and Experimental Dental... Apr 2024This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN). (Review)
Review
OBJECTIVES
This review aimed to compare the effectiveness of three treatments: BTX A, CBZ, and OXB, in managing trigeminal neuralgia (TN).
MATERIAL AND METHODS
We conducted a thorough search for research articles related to our issue using specific keywords on several databases, including Cochrane Central Register of Controlled Trials, Science Direct, Scopus, PubMed, Elsevier, Springer Journals, Ovid Medline, EBSCO, and Web of Science. Our focus was on publications from 1965 to 2023.
RESULTS
We retrieved 46 articles from the search and reviewed them carefully. Out of these, we selected 29 articles that met the inclusion criteria. Among the selected articles, 11 investigated the effects of CBZ and OXB, while 18 explored the impact of BTX A on the improvement of TN symptoms. The response rate ranged between 56% and 90.5% for CBZ and between 90.9% and 94% for OXB. The response rate for BTX A ranged between 51.4% and 100%. All these three treatments had a remarkable effect on the improvement of TN. Importantly, findings highlighted that side effects of CBZ and OXB could lead to treatment discontinuation in some cases, whereas BTX A's side effects have been minimal and less frequent.
CONCLUSIONS
Consequently, BTX A emerges as a promising alternative for TN treatment. However, additional clinical trials are necessary to validate this finding, and further research is required to establish a standardized protocol for administering BTX A in TN.
Topics: Humans; Trigeminal Neuralgia; Botulinum Toxins, Type A; Oxcarbazepine; Carbamazepine; Databases, Factual
PubMed: 38558383
DOI: 10.1002/cre2.882