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Systematic review of antiepileptic drugs' safety and effectiveness in feline epilepsy.

ABSTRACT: Understanding 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.Forty 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.This 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.

SUBMITTER: Charalambous M

PROVIDER: S-EPMC5834883 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Systematic review of antiepileptic drugs' safety and effectiveness in feline epilepsy.

Charalambous Marios M Charalambous Marios M Pakozdy Akos A Bhatti Sofie F M SFM Volk Holger A HA

BMC veterinary research 20180302 1

<h4>Background</h4>Understanding 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 curr ...[more]

PMID: 29499762

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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.

Project description:Background: Intractable epilepsy (IE) is still a major concern in neurology, and existing therapies do not adequately control symptoms. Chinese Herbal Medicine (CHM) has been widely used as an adjunct to antiepileptic drugs (AEDs) for IE. However, because of the contradictory findings reported in previous studies, it is uncertain if the present evidence is robust enough to warrant its usage. The purpose of this meta-analysis was to systematically evaluate the efficacy of the combination of CHM and AEDs for IE. Methods: From inception to September 2021, Medline, Ovid, Embase, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database, and Wanfang Database were searched. Only randomized controlled trials (RCTs) that assessed the efficacy of the combination of CHM and AEDs for IE were included. We defined monthly seizure frequency as the primary outcome. The secondary outcomes included the abnormal rate of electroencephalogram (EEG), seizure duration, quality of life (QoL), and adverse events (AEs). Results: Twenty studies with 1,830 patients were enrolled. Most trials had poor methodological quality. The meta-analysis showed that the combination of CHM and AEDs was more efficient than AEDs alone in reducing monthly seizure frequency [MD = -1.26%, 95% CI (-1.62, -0.91); p < 0.00001], the abnormal rate of EEG [RR = 0.66%, 95% CI (0.53, 0.82); p = 0.0002], and improving the QoL [MD = 6.96%, 95% CI (3.44, 10.49); p = 0.0001]. There was no significant difference in seizure duration between groups. Moreover, the combination of CHM and AEDs significantly reduced the AEs [RR = 0.45%, 95% CI (0.32, 0.64); p < 0.00001]. Conclusion: The combination of CHM and AEDs could improve seizure control by reducing monthly seizure frequency and abnormal rate of EEG with a decreased risk of adverse events in patients with IE. However, these findings must be interpreted carefully due to the high or uncertain risk of bias in the included trials. To provide stronger evidence for the use of CHM combined with AEDs in IE, high-quality RCTs will be urgently warranted in the future.

Project description:OBJECTIVE:Head-to-head randomized controlled trials (RCTs) are the gold standard for assessing comparative treatment effects. In the absence of direct comparisons between all possible antiepileptic drugs (AEDs), however, clinical decision-making in focal (partial onset) epilepsy relies on alternative evidence borne from indirect comparisons including network meta-analyses (NMAs) and from real-world evidence (RWE) studies. We review NMAs and observational RWE studies comparing AEDs in the adjunctive setting to compare the robustness of these methods and to formulate recommendations for future evidence development. METHODS:A literature review identified NMAs and RWE studies comparing AEDs for the adjunctive treatment of focal seizures published between January 2008 and October 2018. NMAs were evaluated for robustness using a framework based on guidelines from the National Institute for Health and Care Excellence Decision Support Unit and the International Society for Pharmacoeconomics and Outcomes Research. RWE studies were evaluated using the GRACE checklist. RESULTS:From a total of 1993 records, 11 NMAs and six RWE studies were eligible. Key limitations identified in the NMAs include nonsystematic selection of RCTs, unexplored heterogeneity between included RCTs in terms of study and patient characteristics, and selection of AEDs and AED doses or dosing strategies that are not reflective of clinical practice. The main limitations of RWE studies concern sample size, design, and analysis methods. Approximately 90% of comparisons between individual AEDs were nonsignificant in the NMAs. None of the RWE studies adjusted for baseline differences between comparator groups; therefore, they lack the validity to make comparative conclusions. SIGNIFICANCE:Current NMAs and RWE studies provide only nominal comparative evidence for AED treatments in focal epilepsy, and should be used with caution for decision-making due to their methodological limitations. To overcome these hurdles, adherence to methodological guidelines and concerted efforts to collect relevant outcome data in the real world are needed.

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Systematic review of antiepileptic drugs' safety and effectiveness in feline epilepsy.

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Systematic review of antiepileptic drugs' safety and effectiveness in feline epilepsy.

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