Detrimental effect of antiepileptic drugs dose in pediatric children with epilepsy in Saudi Arabia: A prospective cohort study.
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ABSTRACT: Abstract
This study aims to evaluate the effect of dose titration for different oral antiepileptic medications among children with epilepsy in Riyadh, Saudi Arabia.A single-center prospective pilot, cohort study was undertaken at a tertiary hospital in Riyadh, Saudi Arabia. All medical records of pediatric patients below the age of 14 years of age who has been newly diagnosed with epilepsy by attending a medical specialist or on a new epileptic treatment plans were enrolled in the study.A total of 76 epileptic patients were screened for 3 months' period and 48 patients were included in this study. Out of the 48 patients, 31 patients followed the regular practice in the titration processes and 17 patients were in the British national formulary (BNF) guideline. Fifteen children who were on monotherapy of levetiracetam were in regular practice guideline experienced poor seizure control with a recorded number of seizure incidence (n = 10). The patient in regular practice guidelines using a combination therapy of phenytoin and levetiracetam were experiencing some behavioral disturbance and sedation effect. Seventeen patients followed in the BNF guideline who were on levetiracetam were experienced less adverse effect (n = 2) with no behavioral changes.The group who followed the regular practice found having a greater incidence of documented adverse effects compared to the patients following the BNF guideline. The titrating antiepileptic medication has a detrimental effect on the pediatric population as observed in this study.
SUBMITTER: Alotaibi BS
PROVIDER: S-EPMC8257875 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour.SettingA single centre prospective observational study.ParticipantsChildren (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit.Primary and secondary outcomesPrimary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes.Results180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR.ConclusionsBehavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children.Trail registration numberEudraCT (2007-000565-37).
| S-EPMC4458612 | biostudies-literature
Project description:ObjectiveThe aim of the study was to determine sociodemographic, biological epilepsy-specific, and adherence predictors of long-term pediatric seizure outcomes.MethodsThis study is a prospective, longitudinal, observational study of antiepileptic drug (AED) adherence and seizure outcomes in children with newly diagnosed epilepsy. Patients were recruited from April 2006 to March 2009 and followed for 2 years. Objective, electronic monitors were used to assess AED adherence. Medical chart reviews assessed medical variables and seizure outcomes.ResultsParticipants (n = 109) were 7.3 ± 2.9 years of age, and 62% male. Four adherence trajectory groups were identified: severe early nonadherence (n = 10), variable nonadherence (n = 16), moderate nonadherence (n = 40), and high adherence (n = 43). Two seizure probability trajectory groups were identified: high seizure (n = 28) and low seizure probability (n = 81). Participants with recognizable syndromes were less likely to be a member of the high seizure probability group (b = -2.372; odds ratio [OR] = 0.093; 95% confidence interval [CI]OR = 0.015, 0.595); those with the presence of epileptiform discharges on EEG were more likely to be in the high seizure probability group (b = 1.649; OR = 5.203; 95% CIOR = 1.422, 19.037). Adherence trajectory group status was a significant predictor of seizure trajectory group status (partial max-rescaled R(2) = 0.13).ConclusionsAdherence trajectories and 2 biological epilepsy-specific variables explain a similar proportion of the variability in longitudinal seizure outcomes. The relationship between AED nonadherence and seizure outcomes is not linear. Early adherence interventions could change the course of seizure outcomes, particularly if variability in adherence was minimized postdiagnosis.
| S-EPMC4248449 | biostudies-literature
Project description:Antiepileptic drugs (AEDs) have many benefits but also many side effects, including aggression, agitation, and irritability, in some patients with epilepsy. This article offers a comprehensive summary of current understanding of aggressive behaviors in patients with epilepsy, including an evidence-based review of aggression during AED treatment. Aggression is seen in a minority of people with epilepsy. It is rarely seizure related but is interictal, sometimes occurring as part of complex psychiatric and behavioral comorbidities, and it is sometimes associated with AED treatment. We review the common neurotransmitter systems and brain regions implicated in both epilepsy and aggression, including the GABA, glutamate, serotonin, dopamine, and noradrenaline systems and the hippocampus, amygdala, prefrontal cortex, anterior cingulate cortex, and temporal lobes. Few controlled clinical studies have used behavioral measures to specifically examine aggression with AEDs, and most evidence comes from adverse event reporting from clinical and observational studies. A systematic approach was used to identify relevant publications, and we present a comprehensive, evidence-based summary of available data surrounding aggression-related behaviors with each of the currently available AEDs in both adults and in children/adolescents with epilepsy. A psychiatric history and history of a propensity toward aggression/anger should routinely be sought from patients, family members, and carers; its presence does not preclude the use of any specific AEDs, but those most likely to be implicated in these behaviors should be used with caution in such cases.
| S-EPMC4931873 | biostudies-other
Project description:ObjectiveTo study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME).MethodsPeople with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12-month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females.ResultsWe included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08-1.13], P < 0.001) and female sex (1.41 [1.07-1.85], P = 0.02) were associated with shorter trial duration. Valproate was associated with the longest treatment duration; trials with carbamazepine and topiramate were significantly shorter (HR [CI]: 3.29 [2.15-5.02], P < 0.001 and 1.93 [1.31-2.86], P < 0.001). The relative frequency of valproate trials shows a decreasing trend since 2003 while there is an increasing trend for levetiracetam. Fewer females than males received valproate (76.2% vs 92.6%, P = 0.001).SignificanceIn people with JME, valproate is an effective AED; levetiracetam emerged as an alternative. Valproate is now contraindicated in women of childbearing potential without special precautions. With appropriate selection and safeguards in place, valproate should remain available as a therapy, including as an alternative for women of childbearing potential whose seizures are resistant to other treatments.
| S-EPMC6698679 | biostudies-literature
Project description:One hundred fifty-one neurologists at U.S. epilepsy centers responded to a survey on stopping medications in patients following successful resective epilepsy surgery. Sixty-two percent said patients should be > or = 2 years seizure-free before stopping medication. Although respondents tended to agree about the importance of many of the queried factors (e.g., focal pathology in favor of and persistent auras against stopping antiepileptic drugs), it is unclear how well these factors determine seizure outcome in this setting.
| S-EPMC1868701 | biostudies-literature
Project description:BackgroundUnderstanding the efficacy and safety profile of antiepileptic drugs (AEDs) in feline epilepsy is a crucial consideration for managing this important brain disease. However, there is a lack of information about the treatment of feline epilepsy and therefore a systematic review was constructed to assess current evidence for the AEDs' efficacy and tolerability in cats. The methods and materials of our former systematic reviews in canine epilepsy were mostly mirrored for the current systematic review in cats. Databases of PubMed, CAB Direct and Google scholar were searched to detect peer-reviewed studies reporting efficacy and/or adverse effects of AEDs in cats. The studies were assessed with regards to their quality of evidence, i.e. study design, study population, diagnostic criteria and overall risk of bias and the outcome measures reported, i.e. prevalence and 95% confidence interval of the successful and affected population in each study and in total.ResultsForty studies describing clinical outcomes of AEDs' efficacy and safety were included. Only two studies were classified as "blinded randomised controlled trials". The majority of the studies offered high overall risk of bias and described low feline populations with unclear diagnostic criteria and short treatment or follow-up periods. Individual AED assessments of efficacy and safety profile showed that phenobarbital might currently be considered as the first choice AED followed by levetiracetam and imepitoin. Only imepitoin's safety profile was supported by strong level of evidence. Imepitoin's efficacy as well as remaining AEDs' efficacy and safety profile were supported by weak level of evidence.ConclusionsThis systematic review reflects an evidence-based assessment of the published data on the AEDs' efficacy and safety for feline epilepsy. Currently, phenobarbital is likely to be the first-line for feline epileptic patients followed by levetiracetam and imepitoin. It is essential that clinicians evaluate both AEDs' effectiveness and tolerability before tailoring AED to the individual patient. Further studies in feline epilepsy treatment are by far crucial in order to establish definite guidelines for AEDs' efficacy and safety.
| S-EPMC5834883 | biostudies-literature
Project description:BackgroundComprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.MethodsElectronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.ResultsA total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.ConclusionGiven the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
| S-EPMC8475226 | biostudies-literature
Project description:ObjectiveAn epilepsy mouse model for Tuberous Sclerosis Complex (TSC) was developed and validated to investigate the mechanisms underlying epileptogenesis. Furthermore, the possible antiepileptogenic properties of commonly used antiepileptic drugs (AEDs) and new compounds were assessed.MethodsTsc1 deletion was induced in CAMK2A-expressing neurons of adult mice. The antiepileptogenic properties of commonly used AEDs and inhibitors of the mTOR pathways were assessed by EEG recordings and by molecular read outs.ResultsMice developed epilepsy in a narrow time window (10 ± 2 days) upon Tsc1 gene deletion. Seizure frequency but not duration increased over time. Seizures were lethal within 18 days, were unpredictable, and did not correlate to seizure onset, length or frequency, reminiscent of sudden unexpected death in epilepsy (SUDEP). Tsc1 gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by RHEB1 gene deletion or rapamycin treatment. However, other inhibitors of the mTOR pathway such as AZD8055 and PF4708671 were ineffective. Except for ketogenic diet, none of commonly used AEDs showed an effect on mTORC1 activity. Vigabatrin and ketogenic diet treatment were able to significantly delay seizure onset. In contrast, survival was shortened by lamotrigine.InterpretationThis novel Tsc1 mouse model is highly suitable to assess the efficacy of antiepileptic and -epileptogenic drugs to treat mTORC1-dependent epilepsy. Additionally, it allows us to study the mechanisms underlying mTORC1-mediated epileptogenesis and SUDEP. We found that early treatment with vigabatrin was not able to prevent epilepsy, but significantly delayed seizure onset.
| S-EPMC6649373 | biostudies-literature
Project description:ObjectiveTo evaluate and compare long-term effectiveness of five antiepileptic drugs (AEDs) for monotherapy of adult patients with focal epilepsy in routine clinical practice.MethodsAdult patients with focal epilepsy, who were prescribed with carbamazepine (CBZ), valproate (VPA), lamotrigine (LTG), topiramate (TPM), or oxcarbazepine (OXC) as monotherapy, during the period from January 2004 to June 2012 registered in Wenzhou Epilepsy Follow Up Registry Database (WEFURD), were included in the study. Prospective long-term follow-up was conducted until June 2013. The endpoints were time to treatment failure, time to seizure remission, and time to first seizure.ResultsThis study included 654 patients: CBZ (n=125), VPA (n=151), LTG (n=135), TPM (n=76), and OXC (n=167). The retention rates of CBZ, VPA, LTG, TPM, and OXC at the third year were 36.1%, 32.4%, 57.6%, 37.9%, and 41.8%, respectively. For time to treatment failure, LTG was significantly better than CBZ and VPA (LTG vs. CBZ, hazard ratio, [HR] 0.80 [95% confidence interval: 0.67-0.96], LTG vs. VPA, 0.53 [0.37-0.74]); TPM was worse than LTG (TPM vs. LTG, 1.77 [1.15-2.74]), and OXC was better than VPA (0.86 [0.78-0.96]). After initial target doses, the seizure remission rates of CBZ, VPA, LTG, TPM, and OXC were 63.0%, 77.0%, 83.6%, 67.9%, and 75.3%, respectively. LTG was significantly better than CBZ (1.44 [1.15-1.82]) and OXC (LTG vs. OXC, 0.76 [0.63-0.93]); OXC was less effective than LTG in preventing the first seizure (1.20 [1.02-1.40]).ConclusionLTG was the best, OXC was better than VPA only, while VPA was the worst. The others were equivalent for comparisons between five AEDs regarding the long-term treatment outcomes of monotherapy for adult patients with focal epilepsy in a clinical practice. For selecting AEDs for these patients among the first-line drugs, LTG is an appropriate first choice; others are reservation in the first-line but VPA is not.
| S-EPMC4493091 | biostudies-literature
Project description:BackgroundPharmacotherapy of epilepsy including antiepileptic drugs (AEDs) is one of the main treatment approaches. As a biological target, sodium channels (Nav channels) and glutamate receptor genes are playing a major role in the etiology and treatment of epilepsy.ObjectiveThis study aims to investigate the genetic associations of certain genetic polymorphisms with increased risk of epilepsy susceptibility and variability in response to AEDs treatment in a Jordanian Arab population.MethodA pharmacogenetics and case-control study on 296 unrelated epileptic Jordanian patients recruited from the pediatric neurology clinic at the Queen Rania Al-Abdullah Hospital (QRAH) in Amman, Jordan and 299 healthy individuals was conducted. Children up to 15 years old which receiving AEDs for at least three months were scanned for genetic association of 7 single nucleotide polymorphisms (SNPs) within three candidate genes (SCN2A, SCN3B and GRM4) with epilepsy susceptibility.ResultsSCN2A rs2304016 (P = 0.04) and GRM4 rs2499697 (P = 0.031) were statistically significant with generalized epilepsy. Haplotype of CAACG GRM4 was genetically associated with epilepsy and partial epilepsy (P = 0.036; P = 0.024, respectively). This study also found that TGTAA genetic haplotype formed within GRM4 gene was associated with generalized epilepsy susceptibility (P = 0.006). While, no significant linkage of SCN3B rs3851100 to either disease susceptibility or drug responsiveness was found.ConclusionThis study identified no significant associations of allelic or genotypic SNPs with the susceptibility of epilepsy and medication response with an exception of rs2304016 and rs2499697 SNPs that were associated with the generalized type of epilepsy among Jordanian population. Further studies are required in different populations to confirm our results and identify genetic factors that involved in susceptibility and treatment response.
| S-EPMC6598501 | biostudies-literature