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Practical Neurology Oct 2021Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic... (Review)
Review
Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic criteria, which subclassify TN on the basis of presence of trigeminal neurovascular conflict or an underlying neurological disorder, should be used as they allow better characterisation of patients and help in decision-making regarding medical and surgical treatments. MR imaging, including high-resolution trigeminal sequences, should be performed as part of the diagnostic work-up. Carbamazepine and oxcarbazepine are drugs of first choice. Lamotrigine, gabapentin, pregabalin, botulinum toxin type A and baclofen can be used either alone or as add-on therapy. Surgery should be considered if the pain is poorly controlled or the medical treatments are poorly tolerated. Trigeminal microvascular decompression is the first-line surgery in patients with trigeminal neurovascular conflict while neuroablative surgical treatments can be offered if MR imaging does not show any neurovascular contact or where patients are considered too frail for microvascular decompression or do not wish to take the risk.
Topics: Anticonvulsants; Carbamazepine; Humans; Magnetic Resonance Imaging; Oxcarbazepine; Trigeminal Neuralgia
PubMed: 34108244
DOI: 10.1136/practneurol-2020-002782 -
Continuum (Minneapolis, Minn.) Feb 2022Seizure disorders are the most frequent major neurologic complication in pregnancy, affecting 0.3% to 0.8% of all gestations. Women of childbearing age with epilepsy... (Review)
Review
PURPOSE OF REVIEW
Seizure disorders are the most frequent major neurologic complication in pregnancy, affecting 0.3% to 0.8% of all gestations. Women of childbearing age with epilepsy require special care related to pregnancy. This article provides up-to-date information to guide practitioners in the management of epilepsy in pregnancy.
RECENT FINDINGS
Ongoing multicenter pregnancy registries and studies continue to provide important information on issues related to pregnancy in women with epilepsy. Valproate poses a special risk for malformations and cognitive/behavioral impairments. A few antiseizure medications pose low risks (eg, lamotrigine, levetiracetam), but the risks for many antiseizure medications remain uncertain. Although pregnancy rates differ, a prospective study found no difference in fertility rates between women with epilepsy who were attempting to get pregnant and healthy controls. During pregnancy, folic acid supplementation is important, and a dose greater than 400 mcg/d during early pregnancy (ie, first 12 weeks) is associated with better neurodevelopmental outcome in children of women with epilepsy. Breastfeeding is not harmful and should be encouraged in women with epilepsy even when they are on antiseizure medication treatment.
SUMMARY
Women with epilepsy should be counseled early and regularly about reproductive health. Practitioners should discuss the risks of various obstetric complications; potential anatomic teratogenicity and neurodevelopmental dysfunction related to fetal antiseizure medication exposure; and a plan of care during pregnancy, delivery, and postpartum. Women with epilepsy should also be reassured that the majority of pregnancies are uneventful.
Topics: Anticonvulsants; Child; Epilepsy; Female; Humans; Multicenter Studies as Topic; Postpartum Period; Pregnancy; Pregnancy Complications; Prospective Studies
PubMed: 35133310
DOI: 10.1212/CON.0000000000001056 -
Neuropsychopharmacology Reports Sep 2021Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by... (Review)
Review
BACKGROUND
Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non-neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents.
METHODS
Randomized controlled trials, observational studies, and evidence-based meta-analyses of ASD efficacy and tolerability as initial monotherapy for epileptic seizures and syndromes were identified in PubMed, EMBASE, the Cochrane Library, and Elsevier Clinical Pharmacology.
RESULTS
The choice of ASD varies primarily according to the seizure type. Practical guidelines for ASD selection in patients with new-onset and drug-resistant epilepsy were recently published. The guidelines have shown that the newer-generation drugs, which have unique mechanistic and pharmacokinetic properties, are better tolerated but have similar efficacy compared with the older drugs. Several ASDs are effective as first-line monotherapy in focal seizures, including lamotrigine, carbamazepine, phenytoin, levetiracetam, and zonisamide. Valproate remains the first-line drug for many patients with generalized and unclassified epilepsies. However, valproate should be avoided, if possible, in women of childbearing potential because of teratogenicity. Toxicity profile precludes several drugs from use as first-line treatment, for example, vigabatrin, felbamate, and rufinamide.
CONCLUSIONS
Antiseizure drugs have different pharmacologic profiles that should be considered when selecting and prescribing these agents for epilepsy. These include pharmacokinetic properties, propensity for drug-drug interactions, and adverse effects.
Topics: Anticonvulsants; Epilepsies, Partial; Epilepsy; Epilepsy, Generalized; Humans; Neuropharmacology; Pharmaceutical Preparations; Seizures; Valproic Acid
PubMed: 34296824
DOI: 10.1002/npr2.12196 -
Current Neuropharmacology 2021It is challenging to balance the fetal risks associated with the use of antiepileptic drugs (AEDs) against maternal and fetal risks of seizure worsening, and therefore... (Review)
Review
Use of Phenytoin, Phenobarbital Carbamazepine, Levetiracetam Lamotrigine and Valproate in Pregnancy and Breastfeeding: Risk of Major Malformations, Dose-dependency, Monotherapy vs Polytherapy, Pharmacokinetics and Clinical Implications.
It is challenging to balance the fetal risks associated with the use of antiepileptic drugs (AEDs) against maternal and fetal risks of seizure worsening, and therefore it is very important to define and distinguish the possible risks entailed by different AEDs. This paper aims to undertake a comprehensive review regarding the possible risks of four classical (phenytoin, carbamazepine, phenobarbital, and valproate) and two newer (lamotrigine and levetiracetam) AEDs during pregnancy. The review focuses on major and organ-specific malformations, dose-dependent risks, mono vs polytherapy, and clinical pharmacokinetics. A discussion regarding the safety of AED use during breastfeeding is also provided.
Topics: Anticonvulsants; Breast Feeding; Carbamazepine; Epilepsy; Female; Humans; Lamotrigine; Levetiracetam; Phenobarbital; Phenytoin; Pregnancy; Pregnancy Complications; Valproic Acid
PubMed: 33573557
DOI: 10.2174/1570159X19666210211150856 -
Medicina (Kaunas, Lithuania) Jun 2021Data regarding older age bipolar disorder (OABD) are sparse. Two major groups are classified as patients with first occurrence of mania in old age, the so called "late... (Review)
Review
Data regarding older age bipolar disorder (OABD) are sparse. Two major groups are classified as patients with first occurrence of mania in old age, the so called "late onset" patients (LOBD), and the elder patients with a long-standing clinical history, the so called "early onset" patients (EOBD). The aim of the present literature review is to provide more information on specific issues concerning OABD, such as epidemiology, aetiology and treatments outcomes. We conducted a Medline literature search from 1970-2021 using the MeSH terms "bipolar disorder" and "aged" or "geriatric" or "elderly". The additional literature was retrieved by examining cross references and by a hand search in textbooks. With sparse data on the treatment of OABD, current guidelines concluded that first-line treatment of OABD should be similar to that for working-age bipolar disorder, with specific attention to side effects, somatic comorbidities and specific risks of OABD. With constant monitoring and awareness of the possible toxic drug interactions, lithium is a safe drug for OABD patients, both in mania and maintenance. Lamotrigine and lurasidone could be considered in bipolar depression. Mood stabilizers, rather than second generation antipsychotics, are the treatment of choice for maintenance. If medication fails, electroconvulsive therapy is recommended for mania, mixed states and depression, and can also be offered for continuation and maintenance treatment. Preliminary results also support a role of psychotherapy and psychosocial interventions in old age BD. The recommended treatments for OABD include lithium and antiepileptics such as valproic acid and lamotrigine, and lurasidone for bipolar depression, although the evidence is still weak. Combined psychosocial and pharmacological treatments also appear to be a treatment of choice for OABD. More research is needed on the optimal pharmacological and psychosocial approaches to OABD, as well as their combination and ranking in an evidence-based therapy algorithm.
Topics: Aged; Anticonvulsants; Antipsychotic Agents; Bipolar Disorder; Humans; Lithium; Valproic Acid
PubMed: 34201098
DOI: 10.3390/medicina57060587 -
Psychopharmacology Bulletin Mar 2021Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The... (Review)
Review
Stevens-Johnson Syndrome (SJS) is a rare life-threatening condition characterized by severe mucocutaneous epidermal necrolysis and detachment of the epidermis. The condition centers around a delayed-type hypersensitivity reaction with a complex etiology stemming from a variety of causes. The number one cause is medication-related-common ones including sulfonamides, antiepileptics, allopurinol, and nonsteroidal anti-inflammatory drugs. Genetics also play a role as several human leukocyte antigen (HLA) genotypes within certain ethnic groups have been implicated in adverse reactions to specific drugs. HLAB*15:02 has been identified in the Chinese and others of Southeast Asian origin to increase susceptibility to lamotrigine and carbamazepine-induced SJS. Furthermore, patients of Japanese origin with HLAB*31:01 and Koreans with HLA-B*44:03 are also at increased risk of SJS after receiving the same two drugs. Of the antiepileptics, one most commonly associated with SJS is lamotrigine, a pre-synaptic voltage-gated sodium channel inhibitor. Lamotrigine is an antiepileptic drug of the phenyltriazine class that is indicated for the prevention of focal and generalized seizures in epileptic patients as well as monotherapy or adjunctive maintenance treatment for Bipolar disorder. The occurrence of SJS is not a rigid contraindication to lamotrigine reintroduction in the same patient. To facilitate this, manufacturers have developed a strict re-challenge dosing regimen to facilitate successful reintroduction of lamotrigine. In order to prevent the recurrence of SJS during a re-challenge, timing of re-dose and initial rash severity must be considered. Therefore, to prevent SJS recurrence, prime lamotrigine re-challenge patients are those with mild initial rash that has not occurred within the previous 4 weeks. The Federal Food and Drug Administration recommends the testing HLA subtypes for those associated with SJS prior to starting lamotrigine.
Topics: Anticonvulsants; Carbamazepine; HLA-B Antigens; Humans; Lamotrigine; Stevens-Johnson Syndrome; United States
PubMed: 34092825
DOI: No ID Found -
Molecular Pain 2020The trigeminal nerve (V) is the fifth and largest of all cranial nerves, and it is responsible for detecting sensory stimuli that arise from the craniofacial area. The... (Review)
Review
The trigeminal nerve (V) is the fifth and largest of all cranial nerves, and it is responsible for detecting sensory stimuli that arise from the craniofacial area. The nerve is divided into three branches: ophthalmic (V1), maxillary (V2), and mandibular (V3); their cell bodies are located in the trigeminal ganglia and they make connections with second-order neurons in the trigeminal brainstem sensory nuclear complex. Ascending projections via the trigeminothalamic tract transmit information to the thalamus and other brain regions responsible for interpreting sensory information. One of the most common forms of craniofacial pain is trigeminal neuralgia. Trigeminal neuralgia is characterized by sudden, brief, and excruciating facial pain attacks in one or more of the V branches, leading to a severe reduction in the quality of life of affected patients. Trigeminal neuralgia etiology can be classified into idiopathic, classic, and secondary. Classic trigeminal neuralgia is associated with neurovascular compression in the trigeminal root entry zone, which can lead to demyelination and a dysregulation of voltage-gated sodium channel expression in the membrane. These alterations may be responsible for pain attacks in trigeminal neuralgia patients. The antiepileptic drugs carbamazepine and oxcarbazepine are the first-line pharmacological treatment for trigeminal neuralgia. Their mechanism of action is a modulation of voltage-gated sodium channels, leading to a decrease in neuronal activity. Although carbamazepine and oxcarbazepine are the first-line treatment, other drugs may be useful for pain control in trigeminal neuralgia. Among them, the anticonvulsants gabapentin, pregabalin, lamotrigine and phenytoin, baclofen, and botulinum toxin type A can be coadministered with carbamazepine or oxcarbazepine for a synergistic approach. New pharmacological alternatives are being explored such as the active metabolite of oxcarbazepine, eslicarbazepine, and the new Nav1.7 blocker vixotrigine. The pharmacological profiles of these drugs are addressed in this review.
Topics: Animals; Anticonvulsants; Baclofen; Botulinum Toxins, Type A; Carbamazepine; Facial Pain; Gabapentin; Humans; Lamotrigine; Oxcarbazepine; Pain Management; Phenytoin; Pregabalin; Quality of Life; Trigeminal Neuralgia
PubMed: 31908187
DOI: 10.1177/1744806920901890 -
Muscle & Nerve Oct 2020The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1... (Review)
Review
The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation. In the absence of genetic confirmation, the diagnosis is supported by detailed electrophysiological testing, exclusion of other related disorders, and analysis of a variant of uncertain significance if present. Symptomatic treatment with a sodium channel blocker, such as mexiletine, is usually the first step in management, as well as educating patients about potential anesthetic complications.
Topics: Acetazolamide; Age of Onset; Carbonic Anhydrase Inhibitors; Chloride Channels; Electrodiagnosis; Electromyography; Fatigue; Genetic Testing; Humans; Lamotrigine; Mexiletine; Muscle Weakness; Muscle, Skeletal; Myalgia; Myotonia Congenita; Myotonic Disorders; NAV1.4 Voltage-Gated Sodium Channel; Practice Guidelines as Topic; Ranolazine; Sodium Channel Blockers; Voltage-Gated Sodium Channel Blockers
PubMed: 32270509
DOI: 10.1002/mus.26887 -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Apr 2022This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, eventrate, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
For the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'. We performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting. Results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA. Network meta-analysis showed high-certainty evidence that for our primary outcome, 'time to treatment failure', for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: eventrate 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and eventrate was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs. For people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or eventrate in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), eventrate 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09). Network meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures. Network meta-analysis also showed high- to moderate-certainty evidence that, for 'time to first seizure,' in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, eventrate, zonisamide and lacosamide) for either seizure type. Generally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results. The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.
AUTHORS' CONCLUSIONS
High-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug eventrate, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and eventrate would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) is needed.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Humans; Network Meta-Analysis; Phenytoin
PubMed: 35363878
DOI: 10.1002/14651858.CD011412.pub4 -
Therapeutic Advances in Neurological... 2022Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy... (Review)
Review
Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy.
PubMed: 35706844
DOI: 10.1177/17562864221101687