LEV is considered “weight-neutral” (Gidal et al., 2003; Briggs and French, 2004). However, weight loss is listed in a study comparing LEV in adult vs ageing patients (Cramer et al., 2003) and four cases of considerable weight loss have been published with LEV used in cotherapy at a dose ranging from 2000 to 3000 mg/day (Hadjikoutis et al., 2003). In the light of our recent clinical experience, we report 19 cases of weight loss associated with LEV but at lower doses and in monotherapy in three patients. These 19 patients were divided in two soubgroups, with LEV as the likely contributing factor vs cases with confounding variables.[…]
Posts Tagged Levetiracetam
[ARTICLE] Levetiracetam for epilepsy: an evidence map of efficacy, safety and economic profiles – Full Text
Objective: To evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.
Materials and methods: PubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.
Results: A total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50–1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79–1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34–5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51–2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90–1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41–0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.
Conclusion: LEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness
Epilepsy ranks fourth after tension-type headache, migraine and Alzheimer disease in the world’s neurological disorders burden.1 A systematic review (SR) and meta-analysis of international studies reported that the point prevalence of active epilepsy was 6.38 per 1,000 people, while the lifetime prevalence was 7.60 per 1,000 people. The annual cumulative incidence of epilepsy was 67.77 per 100,000 people, while the incidence rate was 61.44 per 100,000 person-years.2 As a fairly common clinical condition affecting all ages and requiring long-term, sometimes lifelong, treatment, epilepsy incurs high health care costs for the society.1 In 2010, the total annual cost for epilepsy was 13.8 billion and the total cost per patient was €5,221 in Europe.3 Meanwhile, in the USA, epilepsy-related costs ranged from $1,022 to $19,749 per person annually.4 What is more, drug-refractory epilepsy was a major cost driver,5 with main costs from anticonvulsants, hospitalization and early retirement.6
Currently, antiepileptic drugs (AEDs) are the main treatment method for epilepsy patients, and it was reported that approximately two-thirds of epileptic seizures were controlled by AEDs.7 Conventional AEDs such as carbamazepine (CBZ) and sodium valproate (VPA) have been proven to have good therapeutic effects and low treatment cost. However, some adverse events (AEs) related to these drugs, such as Stevens–Johnson syndrome, menstrual disorder and memory deterioration seriously affect the tolerance and compliance of patients. Compared with conventional AEDs, new AEDs have the potential to be safer, but also more expensive.8
Levetiracetam (LEV) is a novel AED that has been approved as an adjunctive therapy for adults with focal epilepsy since 1999 in the US. In 2006, it was licensed as monotherapy for adults and adolescents above 16 years of age with newly diagnosed focal-onset seizures with or without secondary generalization in Europe. Also, it has been indicated as an adjunctive therapy for partial-onset seizures in patients above 4 years of age in China since 2007. Although the precise mechanism of LEV is still unclear, current researches suggest that its pharmacological mechanism is different from those of other AEDs. It may bind to the synaptic vesicle protein 2A (SV2A), which presents on the synaptic vesicles and some neuroendocrine cells. SV2A may participate in the exocytosis of synaptic vesicles and regulate the release of neurotransmitters, especially the release of excitatory amino acids, and thus depress the epilepsy discharge.9,10 Other possible mechanisms of LEV include the following: selective inhibition of voltage-dependent N-type calcium channels in hippocampal pyramidal cells and reduction of the negative allosteric agents’ inhibition, such as zinc ions and B-carbolines, on glycine and γ-aminobutyric acid neurons, which results in indirectly increasing central nervous system inhibition.11
LEV is almost completely absorbed after oral administration and the absorption is unaffected by food. The bioavailability is nearly 100% and the steady-state concentrations are achieved in 2 days if LEV is taken twice daily. Sixty-six percent of LEV is renally excreted unchanged and its major metabolic pathway is enzymatic hydrolysis of the acetamide group, which is independent of liver CYP/CYP450; so, no clinically meaningful drug–drug interactions with other AEDs were found.12 One published SR of LEV suggested LEV has an equal efficacy compared with conventional AEDs and it is well tolerated for long-term therapy without significant effect on the immune system.13 But in recent years, apart from the most frequent AEs of LEV, such as nausea, gastrointestinal symptoms, dizziness, irritability and aggressive behavior, some rare AEs of LEV have been reported, including eosinophilic pneumonia, rhabdomyolysis, thrombocytopenia, elevated kinase and reduced sperm quality.14–17
Thus, we conducted a mapping review to evaluate the efficacy, safety and economic profiles of LEV compared with all other AEDs for epilepsy, to provide evidence-based information for the rational use of LEV and research agendas.
Maternal use of antiepileptic agents during pregnancy and major congenital malformations in children
Bromley RL, Weston J, Marson AG.
JAMA 2017; 318:1700-1701.
Is maternal use of antiepileptic drugs during pregnancy associated with major congenital malformations in children?
Certain antiepileptic drugs were associated with increased rates of congenital malformations (eg, spina bifida, cardiac anomalies). Lamotrigine (2.31% in 4195 pregnancies) and levetiracetam (1.77% in 817 pregnancies) were associated with the lowest risk and valproate was associated with the highest risk (10.93% in 2565 pregnancies) compared with the offspring of women without epilepsy (2.51% in 2154 pregnancies).
Weston J, Bromley R, Jackson CF, et al. Monotherapy treatment of epilepsy in pregnancy: congenital malformation outcomes in the child. Cochrane Database Syst Rev 2016; 11:CD010224.
Both references are cited in the neurochecklist:
[Abstract] Antiepileptic drug clearances during pregnancy and clinical implications for women with epilepsy
Objective To characterize the magnitude and time course of pregnancy-related clearance changes for different antiepileptic drugs (AEDs): levetiracetam, oxcarbazepine, topiramate, phenytoin, and valproate. A secondary aim was to determine if a decreased AED serum concentration was associated with increased seizure frequency.
Methods Women with epilepsy were enrolled preconception or early in pregnancy and prospectively followed throughout pregnancy and the first postpartum year with daily diaries of AED doses, adherence, and seizures. Study visits with AED concentration measurements occurred every 1–3 months. AED clearances in each trimester were compared to nonpregnant baseline using a mixed linear regression model, with adjustments for age, race, and hours postdose. In women on monotherapy, 2-sample t test was used to compare the ratio to target concentrations (RTC) between women with seizure worsening each trimester and those without.
Results AED clearances were calculated for levetiracetam (n = 18 pregnancies), oxcarbazepine (n = 4), topiramate (n = 10), valproate (n = 5), and phenytoin (n = 7). Mean maximal clearances were reached for (1) levetiracetam in first trimester (1.71-fold baseline clearance) (p = 0.0001), (2) oxcarbazepine in second trimester (1.63-fold) (p = 0.0001), and (3) topiramate in second trimester (1.39-fold) (p = 0.025). In 15 women on AED monotherapy, increased seizure frequency in the first, second, and all trimesters was associated with a lower RTC (p < 0.05).
Conclusion AED clearance significantly changes by the first trimester for levetiracetam and by the second trimester for oxcarbazepine and topiramate. Lower RTC was associated with seizure worsening. Early therapeutic drug monitoring and dose adjustment may be helpful to avoid increased seizure frequency.
Modern treatment of seizures started in 1850 with the introduction of bromides, which was based on the theory that epilepsy was caused by an excessive sex drive. In 1910, phenobarbital (PHB), which then was used to induce sleep, was found to have antiseizure activity and became the drug of choice for many years. A number of medications similar to PHB were developed, including primidone.
In 1938, Houston Merrit and Tracy Putnam described animal models for screening multiple compounds for antiepileptic activity in the Journal of the American Medical Association. In 1940, phenytoin (PHT) was found to be an effective drug for the treatment of epilepsy, and since then it has become a major first-line antiepileptic drug (AED) in the treatment of partial and secondarily generalized seizures.
In 1968, carbamazepine (CBZ) was approved, initially for the treatment of trigeminal neuralgia; later, in 1974, it was approved for partial seizures. Ethosuximide has been used since 1958 as a first-choice drug for the treatment of absence seizures without generalized tonic-clonic seizures. Valproate (VPA) was licensed in Europe in 1960 and in the United States in 1978, and now is widely available throughout the world. It became the drug of choice in primary generalized epilepsies and in the mid 1990s was approved for treatment of partial seizures.
These anticonvulsants were the mainstays of seizure treatment until the 1990s, when newer AEDs with good efficacy, fewer toxic effects, better tolerability, and no need for blood level monitoring were developed. A study of live-born infants in Denmark found that exposure to the newer-generation AEDs lamotrigine, oxcarbazepine, topiramate, gabapentin, and levetiracetam in the first trimester was not associated with an increased risk in major birth defects. 
The new AEDs have been approved in the United States as add-on therapy only, with the exception of topiramate and oxcarbazepine (OXC); lamotrigine (LTG) is approved for conversion to monotherapy. A meta-analysis of 70 randomized clinical trials confirms the clinical impression that efficacy does not significantly differ among AEDs used for refractory partial epilepsy. 
Antiepileptic drugs should be used carefully, with consideration of medication interactions and potential side effects. This is particularly important for special populations, such as patients with HIV/AIDS. 
For more information, see Epilepsy and Seizures.
Mechanism of Action
It is important to understand the mechanisms of action and the pharmacokinetics of antiepileptic drugs (AEDs) so that these agents can be used effectively in clinical practice, especially in multidrug regimens (see the image below).
Many structures and processes are involved in the development of a seizure, including neurons, ion channels, receptors, glia, and inhibitory and excitatory synapses. The AEDs are designed to modify these processes so as to favor inhibition over excitation and thereby stop or prevent seizure activity (see the image below).
The AEDs can be grouped according to their main mechanism of action, although many of them have several actions and others have unknown mechanisms of action. The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below).
For more Visit site —> Antiepileptic Drugs: Overview, Mechanism of Action, Sodium Channel Blockers
[ARTICLE] Eslicarbazepine acetate as a replacement for levetiracetam in people with epilepsy developing behavioral adverse events – Full Text
Psychiatric and behavioral side effects (PBSEs) are a major cause of antiepileptic drug (AED) withdrawal. Levetiracetam (LEV) is a recognized first-line AED with good seizure outcomes but recognized with PBSEs. Eslicarbazepine (ESL) is considered to function similarly to an active metabolite of the commonly used carbamazepine (CBZ). Carbamazepine is used as psychotropic medication to assist in various psychiatric illnesses such as mood disorders, aggression, and anxiety.
The aim was to evaluate the psychiatric profile of ESL in people who had LEV withdrawn due to PBSEs in routine clinical practice to see if ESL can be used as a possible alternative to LEV.
A retrospective observational review was conducted in two UK epilepsy centers looking at all cases exposed to ESL since its licensing in 2010. The ESL group was all patients with treatment-resistant epilepsy who developed intolerable PBSEs to LEV, subsequently trialed on ESL. The ESL group was matched to a group who tolerated LEV without intolerable PBSEs. Psychiatric disorders were identified from case notes. The Hamilton Depression Scale (HAM-D) was used to outcome change in mood. Clinical diagnoses of a mental disorder were compared between groups using the Fisher’s exact test. Group differences in HAM-D scores were assessed using the independent samples t-test (alpha = 0.05).
The total number of people with active epilepsy in the two centers was 2142 of whom 46 had been exposed to ESL. Twenty-six had previous exposure to LEV and had intolerable PBSEs who were matched to a person tolerating LEV. There was no statistical differences in the two groups for mental disorders including mood as measured by HAM-D (Chi-square test: p = 0.28).
The ESL was well tolerated and did not produce significant PBSEs in those who had PBSEs with LEV leading to withdrawal of the drug. Though numbers were small, the findings suggest that ESL could be a treatment option in those who develop PBSEs with LEV and possibly other AEDs.
Epilepsy is a neurological condition with an enduring predisposition to generate seizures and is associated with cognitive, psychological, and social issues . Neuropsychiatric disorders are also more prevalent in people with epilepsy than in the general population  ; . There is, however, still ambiguity as to whether these comorbidities are the result of a direct link such as a genetic predisposition or structural cause leading to seizures and psychiatric problems or if seizures over time lead to psychiatric symptoms .
Treatment strategies in epilepsy need to be tailored to the individual and in particular, clinicians when choosing the appropriate antiepileptic drug (AED) medication need to pay attention not only to seizure patterns but also to a number of different parameters such as age, gender, comorbidities, and cognitive state.
Up to 75% of people with epilepsy may at some point have mental health issues. Antiepileptic drugs also have the potential to impact on mental health and cognition  ; , and treatment with some AEDs is associated with the occurrence of psychiatric and behavioral side effects (PBSEs) while other may have beneficial psychotropic effects ; ;  ; . The PBSEs are often overlooked in epilepsy management and, withdrawal of an AED occurs only if the impact of these symptoms is significant and usually a risk to self or others.
Understanding psychotropic effects of (AEDs) is crucial but knowledge is limited. Carbamazepine (CBZ)-purported mode of action is via the modulation of voltage-sensitive sodium channels. Apart from antiepileptic action, CBZ is also used as a mood stabilizer and has proven efficacy in affective disorders. Oxcarbazepine (OXB) is structurally related to CBZ and is a prodrug that is converted into licarbazepine. The active form licarbazepine is the S enantiomer, known as eslicarbazepine (ESL). The presumed mechanism of action is as for CBZ. Conversely, OXB has never been proven to work as a mood stabilizer. In view of similarities of the postulated mechanism of action but a better tolerability profile, OXB has been used “off label” in mood management.
Levetiracetam (LEV), a commonly prescribed AED in the UK, is associated with PBSEs including irritability, depression, and anxiety  ; . A study suggested that PBSEs occurred in around 17% of people exposed to commonly used AEDs. Nearly 1 in 5 study participants on LEV reported PBSEs to LEV. However for CBZ the reported PBSEs were significantly lower . The ESL did not figure in this study. Another study suggested that PBSEs with ESL were < 2.5%. While side effects such as irritability, anxiety, and aggressive behavior have been associated with other AEDs, rates of aggression and agitation were comparable between ESL and placebo . […]
Daily pyridoxine (vitamin B6) was found to be an effective treatment for the behavioral adverse effects seen with the antiepileptic drug levetiracetam, according to a poster presented at the AES Annual Meeting 2017.
Treatment with levetiracetam (Keppra; UCB) has been shown to cause non-psychotic behavioral effects (eg, aggression, anger, emotional lability, anger, depression, anxiety) in clinical studies (13% in levetiracetam-treated patients vs 6% in placebo-treated). Currently, there is a lack of data regarding the treatment of behavioral effects of levetiracetam, which represents a key cause of treatment discontinuation.
For the retrospective study, Creighton University School of Medicine researchers evaluated whether pyridoxine supplementation could benefit patients who are experiencing behavioral adverse effects due to levetiracetam. The team reviewed electronic medical records of all patients in the Creighton University Epilepsy Center Clinic (2011–2015) for those taking levetiracetam. Forty-five of the 380 total patients receiving levetiracetam (median dose 1000mg daily; highest dose 4000mg daily) were initiated on pyridoxine 100mg daily for symptom control.
The data showed 11.8% of levetiracetam-treated patients experienced behavioral side effects with agitation, insomnia, and irritability being the most commonly observed. These behavioral changes were typically seen within the first month of starting levetiracetam therapy. Nearly all of the patients who received pyridoxine (42/45; 93.3%) remained on levetiracetam therapy as they saw significant improvement in their behavioral symptoms.
“This benefit is seen across the entire range of levetiracetam dosing,” lead author Kalyan Sajja noted. Supplementation with pyridoxine 100mg daily enabled continued treatment with levetiracetam in these patients. The authors added that a large multicenter, prospective, randomized-controlled trial can further validate this clinical benefit.
Sajja K, Sankaraneni R, Galla K, Singh SP. Role of Pyridoxine (Vitamin B6) in the Treatment of Levetiracetam Induced Behavioral Effects in Epilepsy Patients. Presented at: AES annual meeting in Washington, DC. Abstract 1.308.
Objectives. To assess first clinical experiences with Brivaracetam (BRV) in the treatment of epilepsies.
Methods. Data on patients treated with BRV from February to December 2016 and with at least one clinical follow-up were collected from electronic patient records. Data on safety and efficacy were evaluated retrospectively.
Results. In total, 93 patients were analysed; 12 (12.9%) received BRV in monotherapy. Mean duration of follow up was 4.85 months (MD=4 months; SD=3.63). Fifty-seven patients had more than one seizure per month at baseline and had a follow-up of more than 4 weeks; the rate of ≥50% responders was 35.1% (n=20) in this group, of which five (8.8%) patients were newly seizure free.
In 50.5% (47/93), patients were switched from Levetiracetam (LEV) to BRV, of which 43 (46.2%) were switched immediately. Adverse events (AE) occurred in 39.8%, with 22.6% being behavioural, and 25.8% non-behavioural. LEV-related AE (LEV-AE) were significantly reduced by switching to BRV.
The discontinuation of BRV was reported in 26/93 patients (28%); 10 of those were switched back to LEV with an observed reduction of AE in70%.
For clinical reasons, 12 patients received BRV in monotherapy, 75% were seizure free and previous LEV-AE improved in 6/9 patients. BRV-related AE occurred in 5/12 cases, five patients discontinued BRV.
Conclusion. BRV seems to be a safe, easy and effective option in the treatment of patients with epilepsy, especially in the treatment of patients that have psychiatric comorbidities and might not be good candidates for LEV-treatment. BRV broadens the therapeutic spectrum and facilitates personalized treatment.
Background: Levetiracetam is considered a “weight-neutral” drug. We report 19 cases of significant weight loss associated with levetiracetam at a dose ranging from 500 to 2000 mg/day.
Methods: The population was divided into two groups. Group 1 includes patients in whom levetiracetam was the only possible cause of weight loss and Group 2 those in whom other factors may have played a role. Similar cases reported by the French national drug safety center were added (Group 3).
Results: Group 1 included 9 females and 3 males (weight loss ranging from 8.1% to 28.6%). Three patients had levetiracetam in monotherapy. Prior levetiracetam only three were overweight. One patient was hospitalized for a thorough assessment of weight loss. Seven patients reported reduced caloric intake due to decreased pleasure with food. The other five did not report any changes in feeding behavior. Group 2 included seven females with a weight loss ranging from 10% to 26.6%. One patient was on topiramate since two years prior to levetiracetam. Weight loss started with the introduction of levetiracetam. In 4 patients, there was a decreased dosage or cessation of a previous drug known to produce weight gain in some cases simultaneously to the introduction of levetiracetam, but in two of these patients these drugs had not produced any weight gain. Group 3 included only two patients (weight loss: 7 and 20 kg).
Conclusions: This study provides evidence that levetiracetam can cause significant weight loss. Women are at higher risk while initial weight is not a factor.
The dangerous drug attorneys at the Law Offices of Gregory Krasovsky can provide legal advice and representation to individuals and families considering pursuing a Keppra lawsuit. In order for a plaintiff to secure a maximum settlement in litigation of a Keppra claim, regardless of whether in an individual lawsuit or in a class action lawsuit, it is crucial that the law firm representing you have a competent and experienced team of Keppra lawyers to guide you through all of the legal hurdles as well as direct you to sufficient funding (litigation funding or legal finance) to cover pharmaceutical litigation costs. Contact a Keppra attorney today to schedule a free consultation and take your first step to obtaining compensation for losses caused by Keppra side effects.
Keppra, which is generically known as Levetiracetam, is an anticonvulsant drug used to treat epilepsy. Keppra was originally manufactured and marketed by UCB Pharmaceuticals Inc., but now it is available as a generic and is manufactured by a number of firms. Unfortunately, Keppra has a number of serious side effects that can, at times, outweigh its benefits for people who are suffering from epilepsy. Some of the most serious Keppra adverse effects include suicidal tendencies and birth defects.
There are many Levetiracetam side effects. These include, but are not limited to, the following:
- Suicidal Ideation
- Suicidal Tendencies
- Unsteady Walk
- Sore Throat
- Mood Changes
- Changes in Skin Color
- Birth Defects
A 2005 Food and Drug Administration (FDA) study of suicidal ideation in relation to epilepsy drugs has indicated that people taking those drugs, such as Keppra, are twice as likely to suffer from suicidal thoughts as are those who have not been taking these drugs.
Unlike many other drugs, such as Wellbutrin, people taking Keppra are likely to experience suicidal ideation regardless of what age group they might happen to fall into. The aforementioned study tracked almost 30,000 people, and the rick of suicide was spread fairly evenly across the population. Of the 28,000 people who had taken Keppra in this study, four of them had actually committed suicide. These unfortunate incidents serve to confirm the danger of this unsafe drug.
Although Keppra’s ability to cause birth defects is still under investigation, there is some amount of evidence that seems to confirm that Keppra is more harmful to unborn babies than was previously thought. Currently, the FDA has placed Keppra in the Category C for pregnancy, which indicates that there is little human risk. However, AdverseEvents, Inc. believes that Keppra should perhapd be in Category D, which indicates that a significant enough risk to pregnancy exists.
Keppra is similar to another prototypical nootropic drug called piracetam. Keppra is also thought to be a possible treatment for Tourette syndrome, autism, bipolar disorder, and anxiety disorder.
The attorneys at this Keppra law firm believe that drugs should not cause the same ailments that they are meant to cure. If you or your loved one has been injured as a result of taking Keppra, you might be entitled to compensation. Contact our attorneys today to schedule a free consultation.
[Abstract] Can High-Dose Levetiracetam Be Safe? A Case Report of Prolonged Accidental High-Dose Levetiracetam Administration and Review of the Literature
Levetiracetam is an antiepileptic drug that has been used both as adjunctive therapy and monotherapy in pediatric patients with epilepsy. We report a patient with cerebral palsy and epilepsy who took 200 mg/kg per day of levetiracetam for 55 days with no apparent adverse effects. Four other cases of accidental overdose were found in the literature; none of these was associated with any apparent adverse effects. These findings suggest that, in at least some cases, levetiracetam doses much higher than the recommended maximum of 60 mg/kg per day can be administered without apparent adverse effects.