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Epilepsia Mar 2021To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced... (Observational Study)
Observational Study
OBJECTIVE
To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced hyponatremia (COIH).
METHODS
We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia.
RESULTS
A total of 1370 people using CBZ or OXC were identified, of whom 410 had at least one episode of hyponatremia. We checked for symptoms related to the use of CBZ and OXC in 710 people (410 with and 300 without hyponatremia) and found relevant information in 688. Adverse effects occurred in 65% of people with hyponatremia compared to 21% with normal sodium levels (odds ratio [OR] 7.5, P ≤ .001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia (P ≤ .001). Significant predictors of adverse effects were the drug (OXC vs CBZ), and the number of concomitant anti-seizure medications. Dizziness (28% vs 6%), tiredness (22% vs 7%), instability (19% vs 3%), and diplopia (16% vs 4%) were reported more often in the hyponatremia group than in patients with normal levels.
SIGNIFICANCE
People with COIH had a 7-fold increased risk of developing adverse effects during treatment. Clinicians should consider ascertainment of sodium levels in patients taking CBZ and OXC and act upon findings.
Topics: Adult; Anticonvulsants; Carbamazepine; Dizziness; Epilepsy; Fatigue; Female; Humans; Hyponatremia; Male; Middle Aged; Oxcarbazepine; Retrospective Studies; Sodium
PubMed: 33576502
DOI: 10.1111/epi.16828 -
Journal of Epilepsy Research Dec 2023Seizure aggravation in women with epilepsy (WWE) tends to occur at two specific times during the menstrual cycle: the perimenstrual phase and the ovulation period.... (Review)
Review
Seizure aggravation in women with epilepsy (WWE) tends to occur at two specific times during the menstrual cycle: the perimenstrual phase and the ovulation period. Antiseizure drugs (ASDs), especially those that induce enzymes, can accelerate the metabolism of hormones in oral contraceptives, rendering them less effective. Estrogen in contraceptive pills increases the metabolism of lamotrigine. Physiological changes during pregnancy can significantly impact the pharmacokinetics of ASDs, potentially necessitating adjustments in dosage for women with epilepsy to maintain seizure control. The use of valproate in pregnant women is associated with the highest risk of major congenital malformations among ASDs. Risks of major congenital malformations associated with lamotrigine, levetiracetam, and oxcarbazepine were within the range reported in the general population. Exposure to valproate can lead to lower IQ in offspring. Reduced folic acid levels are linked to orofacial clefts, cardiovascular malformations, and urogenital and limb anomalies in WWE. Decreased folate levels are expected with the use of enzyme-inducing ASDs. However, a high dose of folate was associated with an increased risk of cancer in children of mothers with epilepsy. Most ASDs are generally considered safe for breastfeeding and should be encouraged. However, no single ASD is considered ideal for childbearing WWE. Lamotrigine and levetiracetam are relatively more suitable options for this situation.
PubMed: 38223363
DOI: 10.14581/jer.23005 -
EClinicalMedicine Sep 2021Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are...
BACKGROUND
Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear.
METHODS
The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742.
FINDINGS
Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control.
INTERPRETATION
The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin.
FUNDING
none.
PubMed: 34611615
DOI: 10.1016/j.eclinm.2021.101080 -
Cureus Jul 2022Trigeminal neuralgia (TN) is a unilateral, paroxysmal, sharp, shooting, or jabbing pain that occurs in the trigeminal nerve divisions, including the ophthalmic (V1),... (Review)
Review
Trigeminal neuralgia (TN) is a unilateral, paroxysmal, sharp, shooting, or jabbing pain that occurs in the trigeminal nerve divisions, including the ophthalmic (V1), maxillary (V2), and mandibular (V3) nerves. Typically, an episode is triggered by anything touching the face or teeth. TN is a clinical diagnosis with no specific diagnostic test; it is determined by the patient's medical history and pain description. Imaging is necessary to exclude secondary causes. The precise reason for TN is uncertain, but it is commonly believed to result from vascular compression of the trigeminal nerve root, typically near its origin in the pons. There are numerous surgical and medical treatment options available. The most frequently applied medical treatment therapies are carbamazepine and oxcarbazepine. Surgical alternatives are reserved for patients who do not respond to medical treatment. Botulinum toxin A (BTX-A) has emerged as a novel and promising alternative to surgery for individuals whose pain is unresponsive to medication. Multiple studies have established the safety and usefulness of BTX-A in treating TN, with the most significant benefits occurring between six weeks and three months after the surgery. This article reviews various studies published in the last 10 years regarding the therapeutic use of BTX-A in TN. These studies include various observational, clinical, pilot, and animal studies.
PubMed: 35974855
DOI: 10.7759/cureus.26856 -
Epilepsia May 2023Loss-of-function variants in SCN1A cause Dravet syndrome, the most common genetic developmental and epileptic encephalopathy (DEE). However, emerging evidence suggests...
OBJECTIVE
Loss-of-function variants in SCN1A cause Dravet syndrome, the most common genetic developmental and epileptic encephalopathy (DEE). However, emerging evidence suggests separate entities of SCN1A-related disorders due to gain-of-function variants. Here, we aim to refine the clinical, genetic, and functional electrophysiological features of a recurrent p.R1636Q gain-of-function variant, identified in four individuals at a single center.
METHODS
Individuals carrying the recurrent SCN1A p.R1636Q variant were identified through diagnostic testing. Whole cell voltage-clamp electrophysiological recording in HEK-293 T cells was performed to compare the properties of sodium channels containing wild-type Na 1.1 or Na 1.1-R1636Q along with both Na β1 and Na β2 subunits, including response to oxcarbazepine. To delineate differences from other SCN1A-related epilepsies, we analyzed electronic medical records.
RESULTS
All four individuals had an early onset DEE characterized by focal tonic seizures and additional seizure types starting in the first few weeks of life. Electrophysiological analysis showed a mixed gain-of-function effect with normal current density, a leftward (hyperpolarized) shift of steady-state inactivation, and slower inactivation kinetics leading to a prominent late sodium current. The observed functional changes closely paralleled effects of pathogenic variants in SCN3A and SCN8A at corresponding positions. Both wild type and variant exhibited sensitivity to block by oxcarbazepine, partially correcting electrophysiological abnormalities of the SCN1A p.R1636Q variant. Clinically, a single individual responded to treatment with oxcarbazepine. Across 51 individuals with SCN1A-related epilepsies, those with the recurrent p.R1636Q variants had the earliest ages at onset.
SIGNIFICANCE
The recurrent SCN1A p.R1636Q variant causes a clinical entity with a wider clinical spectrum than previously reported, characterized by neonatal onset epilepsy and absence of prominent movement disorder. Functional consequences of this variant lead to mixed loss and gain of function that is partially corrected by oxcarbazepine. The recurrent p.R1636Q variant represents one of the most common causes of early onset SCN1A-related epilepsies with separate treatment and prognosis implications.
Topics: Humans; Infant, Newborn; Epilepsies, Myoclonic; Epilepsy; Gain of Function Mutation; HEK293 Cells; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Oxcarbazepine
PubMed: 36287100
DOI: 10.1111/epi.17444 -
BMC Pediatrics Oct 2023Self-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve...
INTRODUCTION
Self-limited infantile epilepsy (SeLIE) is a benign epilepsy. Previous studies have shown that monotherapy with most antiseizure medications can effectively relieve seizures in patients with SeLIE, but the efficacy of levetiracetam has not been investigated.
OBJECTIVE
This study aimed to investigate the efficacy of levetiracetam in the treatment of SeLIE patients with PRRT2 mutations.
METHODS
The clinical data of 39 SeLIE patients (21 males and 18 females, aged 4.79 ± 1.60 months) with pathogenic variants in PRRT2 or 16p11.2 microdeletion were retrospectively analyzed. Based on the use of initial antiseizure medication (ASM), the patients were classified into two groups: Levetiracetam group (LEG) and Other ASMs group (OAG). The difference of efficacy between the two groups was compared.
RESULTS
Among the 39 SeLIE patients, 16 were LEG (10 males and 6 females, aged 5.25 ± 2.07 months), with whom two obtained a seizure-free status (12.50%) and 14 ineffective or even deteriorated (87.50%). Among the 14 ineffective or deteriorated cases, 13 were seizure-controlled after replacing levetiracetam with other ASMs including topiramate, oxcarbazepine, lamotrigine, and valproate, and the remaining one finally achieved remission at age 3. Of the 39 patients, 23 were OAG (11 males and 12 females; aged 4.48 ± 1.12 months), of whom 22 achieved seizure remission, except for one patient who was ineffective with topiramate initially and relieved by oxcarbazepine instead. Although there were no significant differences in gender and age of onset between the two groups, the effective rate was significantly different (12.50% in LEG vs. 95.65% in OAG) (P < 0.01).
CONCLUSION
The findings showed that patients with SeLIE caused by the PRRT2 mutations did not benefit from the use of levetiracetam, but could benefit from other ASMs.
Topics: Child, Preschool; Female; Humans; Male; Anticonvulsants; Epilepsy; Levetiracetam; Membrane Proteins; Nerve Tissue Proteins; Oxcarbazepine; Retrospective Studies; Seizures; Topiramate; Infant
PubMed: 37880614
DOI: 10.1186/s12887-023-04212-w -
Current Neuropharmacology 2021Exposure in the womb to antiseizure medications and their potential impact on the brain of the developing child has long been researched. Despite this long period of... (Review)
Review
Exposure in the womb to antiseizure medications and their potential impact on the brain of the developing child has long been researched. Despite this long period of interest, this review highlights that above the well-known risks associated with valproate exposure, there are more data required for conclusions regarding all other antiseizure medications. Limited experience with phenytoin and phenobarbital in monotherapy makes clearly defining the risk to later child postnatal functioning difficult, although the evidence of an impact is stronger for phenobarbital than for phenytoin. The widely prescribed lamotrigine is limited in its investigation in comparison to unexposed control children, and whilst it has been demonstrated to carry a lower risk than valproate for certain outcomes, whether it is associated with a more moderate impact on wider aspects of neurodevelopmental functioning is still to be understood. Data for levetiracetam, topiramate and oxcarbazepine are too limited to confidently draw conclusions for most neurodevelopmental outcomes. This slow accumulation of evidence impacts on the safest use of medications in pregnancy and makes counseling women regarding the risks and benefits of specific antiseizure medications difficult. Improved focus, funding, and research methodologies are urgently needed.
Topics: Anticonvulsants; Child; Epilepsy; Female; Humans; Lamotrigine; Oxcarbazepine; Pregnancy; Pregnancy Complications
PubMed: 34279202
DOI: 10.2174/1570159X19666210716111814 -
Brain and Behavior Nov 2022To compare the efficacy and safety of Levetiracetam (LEV) and Oxcarbazepine (OXC) as monotherapy for the treatment of newly diagnosed focal epilepsy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety of Levetiracetam (LEV) and Oxcarbazepine (OXC) as monotherapy for the treatment of newly diagnosed focal epilepsy.
METHODS
We searched PubMed, Cochrane Library, EMBASE, and Google Scholar from January 1, 2000 to May 11, 2022, with no language restrictions along with The ClinicalTrials.gov website and the WHO International Controlled Trials Registry platforms. We pooled the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for the efficacy and safety outcomes. The quality of included trials was assessed using the Cochrane Collaboration's tool.
RESULTS
Two RCTs included a total of 574 newly diagnosed focal epilepsy patients (the LEV group [282 patients] and the OXC group [292 patients]). LEV group when compared with the OXC group had no significant difference in the pooled estimate of seizure freedom at week 24. (RR: 0.81; 95% CI: 0.62-1.05, p = .11). Similarly, there was no significant difference in the pooled estimate of withdrawal due to adverse events (AEs) (RR: 0.87; 95% CI: 0.34-2.23, p = .77). The commonly reported AEs in both trials were dizziness, headache, rash, somnolence, and nasopharyngitis with zero medication-related death and few serious AEs.
CONCLUSIONS
LEV is noninferior to OXC in terms of seizure freedom at week 24 and treatment withdrawal rate due to AEs among adults but long-term treatment data is still missing. Future multicentric double-blinded RCTs and real-world studies are of great need.
Topics: Adult; Humans; Oxcarbazepine; Levetiracetam; Anticonvulsants; Epilepsies, Partial
PubMed: 36184821
DOI: 10.1002/brb3.2779 -
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 -
Epilepsy Research Nov 2023The neonatal and infantile period is the age group with the highest incidence of epilepsy, in which gene variants in sodium and potassium channels are an important...
OBJECTIVE
The neonatal and infantile period is the age group with the highest incidence of epilepsy, in which gene variants in sodium and potassium channels are an important etiology, so the sodium channel blocker class of antiseizure medications may be effective in the treatment of early onset epilepsy. This study aimed to summarize the efficacy and tolerability of oxcarbazepine (OXC) in the treatment of focal epilepsy in neonates and infants under 3 months of age.
METHODS
A retrospective analysis of children with focal epilepsy onset within 3 months of age and treated with OXC in a tertiary pediatric epilepsy center in China was conducted. The efficacy, tolerability and influencing factors of OXC were evaluated.
RESULTS
A total of 50 patients were enrolled, with a median age of epilepsy onset of 11.5 (2, 42) days. There were 32 cases of early infantile developmental and epileptic encephalopathy, 10 cases of self-limited neonatal or neonatal-infantile epilepsy, and 8 cases of focal epilepsy that could not be classified as epileptic syndrome. The median age of application of OXC was 47 (31, 66) days. The median follow-up time was 16.5 (10, 25) months, with 7 deaths. Thirty-eight cases (76.0 %) were effective with OXC treatment, including 28 cases (56.0 %) achieved seizure freedom. Of the 34 cases whose pathogenesis involved genetic factors, 19 cases with sodium/ potassium channel gene variants had higher effective and seizure-free rates than those with other gene variants. The most common adverse event was transient hyponatremia. 2 cases had rash and 2 cases had abnormal electrocardiogram, 3 of which discontinued OXC.
SIGNIFICANCE
This single-center retrospective study suggests that OXC is effective and tolerable for the treatment of focal epilepsy in neonates and infants under 3 months of age. The efficacy of OXC is better in patients with sodium/ potassium channel gene variants.
Topics: Child; Infant, Newborn; Humans; Infant; Oxcarbazepine; Retrospective Studies; Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Sodium; Potassium Channels
PubMed: 37852019
DOI: 10.1016/j.eplepsyres.2023.107240