Long-term efficacy and adverse effects of cannabidiol in adjuvant treatment of drug-resistant epilepsy: a systematic review and meta-analysis
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PROVIDER: S-EPMC10617284 | biostudies-literature | 2023 Jan
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Project description:ObjectiveTo report long-term efficacy and safety results of the SANTE trial investigating deep brain stimulation of the anterior nucleus of the thalamus (ANT) for treatment of localization-related epilepsy.MethodsThis long-term follow-up is a continuation of a previously reported trial of 5- vs 0-V ANT stimulation. Long-term follow-up began 13 months after device implantation with stimulation parameters adjusted at the investigators' discretion. Seizure frequency was determined using daily seizure diaries.ResultsThe median percent seizure reduction from baseline at 1 year was 41%, and 69% at 5 years. The responder rate (≥50% reduction in seizure frequency) at 1 year was 43%, and 68% at 5 years. In the 5 years of follow-up, 16% of subjects were seizure-free for at least 6 months. There were no reported unanticipated adverse device effects or symptomatic intracranial hemorrhages. The Liverpool Seizure Severity Scale and 31-item Quality of Life in Epilepsy measure showed statistically significant improvement over baseline by 1 year and at 5 years (p < 0.001).ConclusionLong-term follow-up of ANT deep brain stimulation showed sustained efficacy and safety in a treatment-resistant population.Classification of evidenceThis long-term follow-up provides Class IV evidence that for patients with drug-resistant partial epilepsy, anterior thalamic stimulation is associated with a 69% reduction in seizure frequency and a 34% serious device-related adverse event rate at 5 years.
| S-EPMC4352097 | biostudies-literature
Project description:Background and purposeThere is a current need to understand the efficacy and quality of life (QoL) outcomes of vagus nerve stimulation (VNS). Identifying patients most likely to benefit from VNS could aid in their selection, reduce side effects, and improve outcomes. Here we studied clinical and QoL outcomes after VNS in patients with drug-resistant epilepsy and attempted to identify response predictors.MethodsThis was a retrospective study of 55 patients with drug-resistant epilepsy treated surgically during 2004-2018, 40 of whom were eligible for inclusion in the analysis. All surgeries were performed using a standard protocol by a neurosurgeon experienced in epilepsy treatment after referral by an attending neurologist. Data were collected from medical records and through a 28-item questionnaire on seizure frequency, duration, and strength before and after VNS, as were the number and type of postoperative complications and their significance to the patient, and QoL based on the 31-item Quality of Life in Epilepsy questionnaire.ResultsImprovements in seizure frequency, duration, and strength were observed in 65% of the patients with drug-resistant epilepsy treated using VNS. The most common complication was hoarseness (70%), and complications were poorly tolerated by 12% of the patients. Repeated surgery to replace batteries or electrodes was required in 20% of the patients. Health status was the only QoL parameter significantly impacted by VNS. No significant efficacy predictors were identified.ConclusionsEfficacy across the first month of treatment is a strong indicator of long-term outcomes of VNS. The stimulator can be removed if it does not provide any benefit.
| S-EPMC11896742 | biostudies-literature
Project description:BackgroundHighly purified cannabidiol (CBD), recently approved for various neurological disorders, is explored as a potential therapeutic avenue for drug-resistant epilepsy (DRE) among adult people with epilepsy (PWE) in this systematic review and meta-analysis.ObjectivesTo conduct an extensive literature review and meta-analysis of CBD use for DRE in adult PWE.DesignSystematic review and meta-analysis.Data sources and methodsWe conducted a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and two electronic resources; we searched Ovid MEDLINE and Scopus using appropriate keywords until August 2023. Data were presented as standardized mean difference (SMD) and odds ratio with confidence interval (CI) via random effect. We appraised the risk of bias of the included studies using the Joanna Briggs Institute critical appraisal tool while their strength of evidence with the Oxford Centre for Evidence-Based Medicine (OCEBM) and Grading of Recommendations Assessment Development and Education (GRADE) Levels of Evidence.ResultsWe identified 16 studies, 3 of which were randomized controlled trials and 3 prospective cohort studies, while the rest were expanded access programs, deriving a total of 668 participants receiving CBD for seizure control. CBD was used concomitantly with antiseizure medications in all studies. There was a statistically significant seizure reduction in the group receiving CBD therapy compared to the placebo group (SMD: -1.50, 95% CI (-3.47, 0.47), p < 0.01).ConclusionThe evidence on CBD use in adult patients with DRE demonstrates a moderate level of certainty according to GRADE level and OCEBM level 2. Further prospective studies involving multiple centers are encouraged to study both the efficacy and safety of CBD in adult patients with DRE.Trial registrationInternational Prospective Register of Systematic Reviews (PROSPERO) 2023 CRD42023449955.
| S-EPMC11775975 | biostudies-literature
Project description:ObjectiveTo investigate feasibility, safety, and tolerability of long-term (48 weeks) add-on treatment with triheptanoin (UX007), the triglyceride of heptanoate, in adults with drug-resistant epilepsy.MethodsThis extension study was offered to adult participants with drug-resistant epilepsy who completed a 12-week randomized controlled trial of add-on medium-chain triglycerides (MCT) vs triheptanoin. Participants were asked to titrate triheptanoin to their maximum tolerated dose over 3 weeks, followed by 48-week maintenance before tapering or treatment extension. The primary aims were to assess retention and safety of the triheptanoin treatment, and secondary aims to assess the tolerated doses and changes in seizure frequency.ResultsEleven adults were enrolled and ten people were analyzed (because one patient was diagnosed as having nonepileptic seizures while on the study). Two adults finished the study and extended their treatment. Eight participants withdrew from the study, due to lack of efficacy (n = 3), unknown reasons (n = 2), belief of weight gain (n = 1), wanting to try a different treatment (n = 1), and a colonoscopy (n = 1). Diarrhea in two people and bloating in one person were deemed possibly related to treatment, but other adverse events were not. The duration of maintenance treatment dose was 27-513 days (median 247 days, range 27-513 days), and 0.49 -1.1 mL/kg triheptanoin was taken per day (0.77 ± 0.19 mL/kg, mean ± standard deviation, 40-100 mL/d). Two participants experienced >90% and three people >50% reduction in seizure frequency, and all had focal seizures. The median seizure reduction was 48% (average 38%).SignificanceOur results indicate antiseizure effects of triheptanoin on focal seizures in 5 out of 10 adults. However, only two people finished and extended the 48-week add-on treatment phase, despite lack of safety or tolerability issues.More studies focused on improved treatment formulations, the potential of lower dosages, and efficacy are needed. Trial registration number: ACTRN12615000406505.
| S-EPMC7278596 | biostudies-literature
Project description:ObjectiveFor people with drug-resistant epilepsy, the use of epilepsy surgery is low despite favorable odds of seizure freedom. To better understand surgery utilization, we explored factors associated with inpatient long-term EEG monitoring (LTM), the first step of the presurgical pathway.MethodsUsing 2001-2018 Medicare files, we identified patients with incident drug-resistant epilepsy using validated criteria of ≥2 distinct antiseizure medication (ASM) prescriptions and ≥1 drug-resistant epilepsy encounter among patients with ≥2 years pre- and ≥1 year post-diagnosis Medicare enrollment. We used multilevel logistic regression to evaluate associations between LTM and patient, provider, and geographic factors. We then analyzed neurologist-diagnosed patients to further evaluate provider/environmental characteristics.ResultsOf 12 044 patients with incident drug-resistant epilepsy diagnosis identified, 2% underwent surgery. Most (68%) were diagnosed by a neurologist. In total, 19% underwent LTM near/after drug-resistant epilepsy diagnosis; another 4% only underwent LTM much prior to diagnosis. Patient factors most strongly predicting LTM were age <65 (adjusted odds ratio 1.5 [95% confidence interval 1.3-1.8]), focal epilepsy (1.6 [1.4-1.9]), psychogenic non-epileptic spells diagnosis (1.6 [1.1-2.5]) prior hospitalization (1.7, [1.5-2]), and epilepsy center proximity (1.6 [1.3-1.9]). Additional predictors included female gender, Medicare/Medicaid non-dual eligibility, certain comorbidities, physician specialties, regional neurologist density, and prior LTM. Among neurologist-diagnosed patients, neurologist <10 years from graduation, near an epilepsy center, or epilepsy-specialized increased LTM likelihood (1.5 [1.3-1.9], 2.1 [1.8-2.5], 2.6 [2.1-3.1], respectively). In this model, 37% of variation in LTM completion near/after diagnosis was explained by individual neurologist practice and/or environment rather than measurable patient factors (intraclass correlation coefficient 0.37).SignificanceA small proportion of Medicare beneficiaries with drug-resistant epilepsy completed LTM, a proxy for epilepsy surgery referral. While some patient factors and access measures predicted LTM, non-patient factors explained a sizable proportion of variance in LTM completion. To increase surgery utilization, these data suggest initiatives targeting better support of neurologist referral.
| S-EPMC10472378 | biostudies-literature
Project description:ImportanceEpilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with several different adverse events (AEs).ObjectiveTo investigate the frequency and risk of AEs developing in patients with epilepsy who are using CBD.Data sourcesPubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published from database inception up to August 4, 2022. The search strategy included a combination of the following keywords: (cannabidiol OR epidiolex) AND (epilepsy OR seizures).Study selectionThe review included all randomized clinical trials that investigated at least 1 AE from the use of CBD in patients with epilepsy.Data extraction and synthesisBasic information about each study was extracted. I2 statistics were calculated using Q statistics to assess the statistical heterogeneity among the included studies. A random-effects model was used in cases of substantial heterogeneity, and a fixed-effects model was used if the I2 statistic for the AEs was lower than 40%. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.Main outcomes and measuresFrequency of each AE and risk of developing each AE in patients with epilepsy using CBD.ResultsNine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs. The overall risk ratios (RRs) for any grade and severe grade AEs were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively, for the CBD group compared with the control group. Compared with the control group, the CBD group had a greater risk for incidence of serious AEs (RR, 2.67; 95% CI, 1.83-3.88), AEs resulting in discontinuation (RR, 3.95; 95% CI, 1.86-8.37), and AEs resulting in dose reduction (RR, 9.87; 95% CI, 5.34-14.40). Because most of the included studies had some risk of bias (3 raised some concerns and 3 were at high risk of bias), these findings should be interpreted with some caution.Conclusions and relevanceIn this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several AEs. Additional studies are needed to determine the safe and effective CBD dosage for treating epilepsy.
| S-EPMC10119734 | biostudies-literature
Project description:BackgroundApproximately 30% of dogs with idiopathic epilepsy (IE) are drug-resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE.ObjectiveTo evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug-resistant IE.AnimalsFifty-one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial.MethodsDouble-blinded placebo-controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1-month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial.ResultsAt the 9 mg/kg/day dose, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05).Conclusions and clinical importanceCannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs.
| S-EPMC10658598 | biostudies-literature
Project description:AimsTo predict the vagus nerve stimulation (VNS) efficacy for pediatric drug-resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi-modal feature set with high prediction accuracy.MethodsSixty-five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups.ResultsThe proportion of VNS responders was 58.5% (38/65) at the last follow-up. In the analysis of parieto-occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central-frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838.ConclusionOur results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto-occipital region, and less spectral complexity of θ brain activities in the central-frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model.
| S-EPMC11252558 | biostudies-literature
Project description:BackgroundDrug-resistant epilepsy (DRE) affects approximately one-third of epilepsy patients who do not achieve adequate seizure control with medication. Vagus nerve stimulation (VNS) is an adjunctive therapy for DRE, but its long-term effects on cortical excitability remain unclear.ObjectivesThis study aims to elucidate the long-term effects of VNS on electroencephalography (EEG) aperiodic components in patients with DRE. Our objective is to identify biomarkers that can serve as indicators of therapeutic efficacy and provide mechanistic insights into the underlying neural processes.DesignThis longitudinal observational study focused on patients with DRE undergoing VNS therapy at Sanbo Brain Hospital. The reduction in seizure frequency rates was quantified over short-term (⩽1 year), medium-term (1-3 years), and long-term (⩾3 years) intervals to assess the therapeutic efficacy of VNS. Both the periodic and aperiodic components of EEG data were analyzed.MethodsAdvanced signal processing techniques were utilized to parameterize the periodic and aperiodic components of EEG data, focusing particularly on "offset" and "exponent." These measures were compared before and after VNS therapy. Correlation analyses were conducted to explore the relationship between these EEG parameters and clinical outcomes.ResultsIn all, 18 patients with DRE participated in this study. During the long-term follow-up period, the responder rate was 55.56%. Significant decreases were observed in aperiodic offset (p = 0.022) and exponent (p = 0.039) among responders. The impact of age on these results was not significant. Correlation analyses revealed a negative association between therapeutic efficacy and a decrease in offset (R = -0.546, p = 0.019) and exponent (R = -0.636, p = 0.019).ConclusionEEG aperiodic parameters, including offset and exponent, have the potential to serve as promising biomarkers for evaluating the efficacy of VNS. An understanding of the regulatory influence of VNS on cortical excitability through these aperiodic parameters could provide a basis for the development of more effective stimulation parameters and therapeutic strategies.
| S-EPMC11452897 | biostudies-literature
Project description:ImportanceDespite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions.ObjectiveTo evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy.Data sourcesSystematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy.Study selectionRandomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers.Data extraction and synthesisData extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve.Main outcomes and measuresShort-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes.ResultsOf 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event-related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes.Conclusions and relevanceThis study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.
| S-EPMC9887534 | biostudies-literature