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The Cochrane Database of Systematic... Nov 2016Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory... (Review)
Review
BACKGROUND
Most people with epilepsy have a good prognosis and their seizures can be well controlled with the use of a single antiepileptic drug, but up to 30% develop refractory epilepsy, especially those with partial seizures. In this review we summarize the current evidence regarding oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy.
OBJECTIVES
To evaluate the effects of oxcarbazepine when used as an add-on treatment for drug-resistant partial epilepsy.
SEARCH METHODS
We searched the Cochrane Epilepsy Group's Specialized Register (28 March 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to March 2006). No language restrictions were imposed. We checked the reference lists of retrieved studies for additional reports of relevant studies. We also contacted Novartis (manufacturers of oxcarbazepine) and experts in the field.
SELECTION CRITERIA
Randomized, placebo-controlled, double-blinded, add-on trials of oxcarbazepine in patients with drug-resistant partial epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and extracted the relevant data. The following outcomes were assessed : (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary odds ratios were estimated for each outcome.
MAIN RESULTS
Two trials were included representing 961 randomized patients.Overall Odds Ratio (OR) (95% Confidence Interval (CIs)) for 50% or greater reduction in seizure frequency compared to placebo 2.96 (2.20, 4.00).Treatment withdrawal OR (95% CIs) compared to placebo 2.17 (1.59, 2.97).Side effects: OR (99% CIs) compared to placebo, ataxia 2.93 (1.72, 4.99); dizziness 3.05 (1.99, 4.67); fatigue 1.80 (1.02, 3.19); nausea 2.88 (1.77, 4.69); somnolence 2.55 (1.84, 3.55); diplopia 4.32 (2.65, 7.04), were significantly associated with oxcarbazepine.
AUTHORS' CONCLUSIONS
Oxcarbazepine has efficacy as an add-on treatment in patients with drug-resistant partial epilepsy, both in adults and children. However, trials reviewed were of relatively short duration, and provide no evidence about the long-term effects of oxcarbazepine. Results cannot be extrapolated to monotherapy or to patients with other epilepsy types.
Topics: Adult; Anticonvulsants; Carbamazepine; Child; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Humans; Outcome Assessment, Health Care; Oxcarbazepine; Randomized Controlled Trials as Topic
PubMed: 27845825
DOI: 10.1002/14651858.CD002028.pub2 -
Frontiers in Pharmacology 2022We conducted meta-analysis to demonstrate the efficacy and safety of ketamine on postoperative catheter-related bladder discomfort (CRBD). A systematic search was...
We conducted meta-analysis to demonstrate the efficacy and safety of ketamine on postoperative catheter-related bladder discomfort (CRBD). A systematic search was performed through PubMed, Embase, and Cochrane Library to identify all randomized controlled trials that used ketamine in postoperative CRBD. This study was carried out by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We used RevMan version 5.3.0. to analyze the data. Five RCTs involving 414 patients were included in the analysis. The incidence and severity of postoperative CRBD were assessed at 0, 1, 2, and 6 h. According to our results of meta-analysis, ketamine reduced the incidence of postoperative CRBD at 2 h (RR 0.39; 95% CI, 0.21-0.71; = 0.002, I = 40%) and 6 h (RR 0.29; 95% CI, 0.16-0.50; < 0.0001, I = 0%) significantly; however, there were no statistical differences at 0 h (RR 0.81; 95% CI, 0.35-1.88; = 0.62, I = 96%) and 1 h (RR 0.57; 95% CI, 0.13-2.54; = 0.46, I = 97%). In two studies, we compared the incidence of moderate-to-severe CRBD between groups according to the scaling system (none, mild, moderate, and severe), and data are presented as numbers. Patients in the ketamine group showed a significantly lower severity of CRBD than those in the placebo group at 1 h (RR 0.09; 95% CI, 0.03-0.31; = 0.0001) and 2 h (RR 0.06; 95% CI, 0.01-0.44; = 0.005). In contrast, there were no meaningful differences between the two groups in the severity of CRBD at 0 h (RR 0.18; = 0.84) or 6 h (RR 0.20; 95% CI, 0.03-1.59; = 0.13). There were no meaningful differences on the rate of adverse events between the ketamine group and control group, mainly including postoperative nausea and vomiting (RR 1.24; 95% CI, 0.89-1.72; = 0.21), diplopia (RR 3.00; 95% CI, 0.48-18.67; = 0.24), and hallucination (RR 3.00; 95% CI, 0.32-28.24; = 0.34). Our meta-analysis demonstrated that a sub-hypnotic dose of ketamine administration can reduce the incidence and severity of postoperative CRBD without causing evident side effects.
PubMed: 35833034
DOI: 10.3389/fphar.2022.816995 -
Journal of Clinical Medicine May 2023This study aimed to perform a systematic review and meta-analysis to compare pre-shaped implants on a patient-specific 3D-printed (3DP) model to manual free-hand shaping... (Review)
Review
Is the Pre-Shaping of an Orbital Implant on a Patient-Specific 3D-Printed Model Advantageous Compared to Conventional Free-Hand Shaping? A Systematic Review and Meta-Analysis.
This study aimed to perform a systematic review and meta-analysis to compare pre-shaped implants on a patient-specific 3D-printed (3DP) model to manual free-hand shaping (MFS) for orbital wall reconstruction. The PRISMA protocol was followed in this study, and the review was registered in the PROSPERO database (CRD42021261594). A search was conducted in MEDLINE (PubMed), Embase, Cochrane Library, Clinicaltrials.gov, Google Scholar, and the grey literature. Ten articles were included, and six outcomes were analyzed. In total, 281 patients were in the 3DP group and 283 were in the MFS group. The studies had an overall high risk of bias. 3DP models resulted in a better accuracy of fit, anatomical angle reproduction, and defect area coverage. The correction of orbital volume was also superior with statistical significance. There was a higher percentage of the correction of enophthalmos and diplopia in the 3DP group. Intraoperative bleeding and hospital stay were reduced in the 3DP group. The meta-analysis of operative time showed a reduction in the average operative time by 23.58 min (95% CI: -43.98 to -3.19), which was statistically significant (t(6) = -2.8299, = 0.0300). The 3DP models appear advantageous for an accurate orbital wall reconstruction, with fewer complications than those for conventional free-hand-shaped implants.
PubMed: 37240532
DOI: 10.3390/jcm12103426 -
Cureus Jul 2020Lemierre's syndrome (LS), once known as "the forgotten disease," is a rare and potentially life-threatening condition that has had a gain in incidence over the last 30... (Review)
Review
Lemierre's syndrome (LS), once known as "the forgotten disease," is a rare and potentially life-threatening condition that has had a gain in incidence over the last 30 years due to a variety of factors that could include changes in antibody prescription patterns, particularly in regard to the treatment of pharyngitis/tonsillitis. Due to its low incidence and broad spectrum of symptoms, LS does not have an obvious clinical diagnosis and can confuse the clinician managing the patient. Furthermore, it is equally difficult to treat patients suffering from LS as it requires a multidisciplinary approach from multiple subspecialties. Thus, communication between hospitalists, radiologists, otolaryngologists, neurologists, and ophthalmologists is critical towards quickly diagnosing the disease condition so that prompt antibiotics, anticoagulation, and surgical intervention can occur. Atypical presentations can also exist, making the diagnosis and management exponentially more challenging. Ophthalmologic symptoms are a particularly rare and atypical presentation of LS. These rare symptoms in LS can be terrifying for patients and providers alike; yet, there does not seem to be any modern medical literature that summarizes ophthalmologic complications for LS patients. To our knowledge, this is the first systematic review of LS with a focus on ophthalmologic complications that has been done. The main objective of this review paper is to provide an up-to-date literature review of LS epidemiology, pathophysiology, diagnosis, and treatment while also performing a novel systematic review of reported cases of LS with ophthalmological complications. We hope to bring more awareness towards LS and its atypical presentations so that physicians will be better able to rapidly diagnose and treat their patients in order to minimize long-term morbidity and mortality.
PubMed: 32742884
DOI: 10.7759/cureus.9326 -
Annals of Medicine and Surgery (2012) Feb 2024Fractures of the orbit are common injuries within the maxillofacial skeleton, and can often result in restrictions to ocular movement, diplopia, and enophthalmous if... (Review)
Review
INTRODUCTION
Fractures of the orbit are common injuries within the maxillofacial skeleton, and can often result in restrictions to ocular movement, diplopia, and enophthalmous if herniation of globe content occurs. Various studies have demonstrated the use of autologous cartilage grafts in the reconstruction of orbital fractures.
METHODS
A systematic review protocol was registered with PROSPERO, and reported in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses. Comprehensive electronic search strategies of four databases were developed. Studies were screened according to the inclusion and exclusion criteria by two independent reviewers.
RESULTS
Seven thousand one hundred seventy-one articles were identified following a comprehensive literature search. These articles were filtered for relevance and duplication, which reduced the number of articles to 16. A total of 259 patients underwent orbital reconstruction with the use of autologous cartilage. Conchal cartilage was harvested in 148 patients, auricular cartilage in 22 patients, nasoseptal cartilage in 72 patients, and costal cartilage in 17 patients. Thirty, seven, twelve, and four complications were observed in patients where cartilage was harvested from the concha, auricle, nasoseptum and rib, respectively. Most common complications included diplopia (=23), infra-orbital para/anaesthesia (=27), and enophthalmos (=7). No failure of graft or donor site morbidity were observed in the studies.
CONCLUSION
Autogenous materials such as cartilage can be used as an alternative for orbital reconstruction. Cartilage was considered by the authors to provide adequate structural support to the orbital contents, and that it was easy to harvest, shape, and position.
PubMed: 38333240
DOI: 10.1097/MS9.0000000000001598 -
International Journal of Oral and... Jun 2022Computed tomography (CT) is commonly used for the diagnosis, treatment planning, and prognosis of pure orbital fractures of the orbital floor and medial wall. The aim of... (Review)
Review
Computed tomography (CT) is commonly used for the diagnosis, treatment planning, and prognosis of pure orbital fractures of the orbital floor and medial wall. The aim of this study was to systematically review the current literature in order to establish an overview of CT parameters relevant to the choice of treatment and (long-term) clinical outcome for patients treated operatively and conservatively. The PRISMA guidelines were followed. Databases were searched using the terms 'orbital fracture' and 'computed tomography'. Studies evaluating the relationship between CT parameters and the treatment decision or clinical outcome (enophthalmos, diplopia, and/or limitation of ocular movement) were included. The search yielded 4448 results of which 31 were included (except for three, all were retrospective). The systematic use of CT imaging in orbital fractures of the floor and the medial wall can be of great value in the treatment decision and prediction of (long-term) clinical outcomes for both conservatively and surgically treated patients. The following parameters were found to be the most relevant: fracture size, fracture location, orbital volume, soft tissue involvement, and craniocaudal dimension. Although some show great individual potential, it is likely that incorporating all parameters into an algorithm will provide the best predictive power and thus would be the most practically applicable tool.
Topics: Diplopia; Enophthalmos; Humans; Orbital Fractures; Retrospective Studies; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 34696942
DOI: 10.1016/j.ijom.2021.10.001 -
The Cochrane Database of Systematic... May 2021This is an updated version of the Cochrane review published in 2015. Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an updated version of the Cochrane review published in 2015. Around half of people with epilepsy will not achieve seizure freedom on their first antiepileptic drug; many will require add-on therapy. Around a third of people fail to achieve complete seizure freedom despite multiple antiepileptic drugs. Lacosamide has been licenced as an add-on therapy for drug-resistant focal epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of lacosamide as an add-on therapy for children and adults with drug-resistant focal epilepsy.
SEARCH METHODS
We searched the following databases (22 August 2019): the Cochrane Register of Studies (CRS Web), including the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946 to 20 August 2019), ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP), with no language restrictions. We contacted UCB Pharma (sponsors of lacosamide).
SELECTION CRITERIA
Randomised controlled trials of add-on lacosamide in people with drug-resistant focal epilepsy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology, assessing the following outcomes: 50% or greater reduction in seizure frequency; seizure freedom; treatment withdrawal; adverse events; quality of life; and cognitive changes. The primary analyses were intention-to-treat. We estimated summary risk ratios (RR) for each outcome presented with 99% confidence intervals (CI), except for 50% or greater seizure reduction, seizure freedom and treatment withdrawal which were presented with 95% CIs. We performed subgroup analyses according to lacosamide dose and sensitivity analyses according to population age, whereby data from children were excluded from the meta-analysis.
MAIN RESULTS
We included five trials (2199 participants). The risk of bias for all studies was low to unclear. All studies were placebo-controlled and assessed doses from 200 mg to 600 mg per day. One study evaluated lacosamide in children; all other studies were in adults. Trial duration ranged from 24 to 26 weeks. All studies used adequate methods of randomisation and were double-blind. Overall, the certainty of the evidence for the outcomes was judged as moderate to high, with the exception of seizure freedom which was low. The RR for a 50% or greater reduction in seizure frequency for all doses of lacosamide compared with placebo was 1.79 (95% CI 1.55 to 2.08; 5 studies; 2199 participants; high-certainty evidence). The RR for seizure freedom for all doses of lacosamide compared with placebo was 2.27 (95% CI 1.35 to 3.83; 5 studies; 2199 participants; low-certainty evidence). The RR for treatment withdrawal for all doses of lacosamide compared with placebo was 1.57 (95% CI 1.24 to 1.98; 5 studies; 2199 participants; moderate-certainty evidence). The estimated effect size for most outcomes did not change considerably following sensitivity analysis. For seizure freedom, however, the RR nearly doubled upon the exclusion of data from children (RR 4.04, 95% CI 1.52 to 10.73). Adverse events associated with lacosamide included: abnormal co-ordination (RR 6.12, 99% CI 1.35 to 27.77), blurred vision (RR 4.65, 99% CI 1.24 to 17.37), diplopia (RR 5.59, 99% CI 2.27 to 13.79), dizziness (RR 2.96, 99% CI 2.09 to 4.20), nausea (RR 2.35, 99% CI 1.37 to 4.02), somnolence (RR 2.04, 99% CI 1.22 to 3.41), vomiting (RR 2.94, 99% CI 1.54 to 5.64), and number of participants experiencing one or more adverse events (RR 1.12, 99% CI 1.01 to 1.24). Adverse events that were not significant were: vertigo (RR 3.71, 99% CI 0.86 to 15.95), rash (RR 0.58, 99% CI 0.17 to 1.89), nasopharyngitis (RR 1.41, 99% CI 0.87 to 2.28), headache (RR 1.34, 99% CI 0.90 to 1.98), fatigue (RR 2.11, 99% CI 0.92 to 4.85), nystagmus (RR 1.47, 99% CI 0.61 to 3.52), and upper respiratory tract infection (RR 0.70, 99% CI 0.43 to 1.15).
AUTHORS' CONCLUSIONS
Lacosamide is effective and well-tolerated in the short term when used as add-on treatment for drug-resistant focal epilepsy. Lacosamide increases the number of people with 50% or greater reduction in seizure frequency and may increase seizure freedom, compared to placebo. Higher doses of lacosamide may be associated with higher rates of adverse events and treatment withdrawal. Additional evidence is required assessing the use of lacosamide in children and on longer-term efficacy and tolerability.
Topics: Adult; Anticonvulsants; Bias; Child; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsies, Partial; Humans; Lacosamide; Placebos; Randomized Controlled Trials as Topic; Seizures
PubMed: 33998660
DOI: 10.1002/14651858.CD008841.pub3 -
The Cochrane Database of Systematic... Mar 2015Nonarteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden and painless loss of vision in the eye, accompanied by pallid swelling of the optic... (Review)
Review
BACKGROUND
Nonarteritic anterior ischemic optic neuropathy (NAION) is characterized by sudden and painless loss of vision in the eye, accompanied by pallid swelling of the optic disc. Its etiology is unknown and no medical therapy has been proven effective in treating this condition. Optic nerve decompression surgery, a proposed treatment for NAION, involves making two or more slits or a window in the tissue surrounding the optic nerve, thereby allowing cerebrospinal fluid to escape, and theoretically reducing the pressure surrounding the optic nerve.
OBJECTIVES
The objective of this review was to assess the safety and efficacy of surgery compared with other treatment or no treatment in people with NAION.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2014), EMBASE (January 1980 to October 2014), PubMed (1948 to October 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 23 October 2014.
SELECTION CRITERIA
All randomized trials of surgical treatment of NAION were eligible for inclusion in this review.
DATA COLLECTION AND ANALYSIS
From full-text copies of all reports from relevant trials, one author extracted data which were verified by another author. No data synthesis was required.
MAIN RESULTS
The one included trial, in which 258 participants were randomized, was stopped early for futility. At the time of the 24-month report the follow-up rate was 95.3% for six months and 67.4% for 24 months (174 participants; 89 careful follow-up and 85 surgery). There was no evidence of a benefit of surgery on visual acuity. Measurements of visual acuity and visual fields were performed by a technician masked to the treatment received. At six months 32.0% of the surgery group had improved visual acuity by 3 or more lines compared with 42.6% of the careful follow-up group (unadjusted risk ratio (RR) 0.75, 95% confidence interval (CI) 0.54 to 1.04). At 24 months 29.4% of the surgery group had improved compared with 31.0% of the careful follow-up group (unadjusted RR 0.95, 95% CI 0.60 to 1.49). Participants who underwent surgery more often lost 3 or more lines of visual acuity in the study eye, although the increased risk was not statistically significant. At six months 18.9% in the surgery group had worsened visual acuity in the study eye compared with 14.8% in the careful follow-up group (RR 1.28; 95% CI 0.73 to 2.24). At 24 months 20.0% in the surgery group had worsened visual acuity in the study eye compared with 21.8% in the careful follow-up group (RR 0.92; 95% CI 0.51 to 1.64). Participants who received surgery experienced both intraoperative and postoperative adverse events, including central retinal artery occlusion during surgery and light perception vision at six months (one participant); and immediate loss of light perception following surgery and loss of vision that persisted to the 12-month visit (two participants). In the careful follow-up group, two participants had no light perception at the six-month follow-up visit; one of these had improved to light perception at 12 months. Pain was the most common adverse event in the surgery group (17% in surgery group versus 3% in the careful follow-up group at one week). Diplopia (double vision) was the next most common complication (8% in the surgery group versus 1% in the careful follow-up group at one week); at three months there was no statistically significant difference in proportion of participants with diplopia between the two groups.
AUTHORS' CONCLUSIONS
The only eligible trial provided no evidence of a beneficial effect of optic nerve decompression surgery for NAION. Future research should focus on increasing our understanding of the etiology and prognosis of NAION. New treatment options should be examined in the context of randomized clinical trials.
Topics: Early Termination of Clinical Trials; Humans; Optic Neuropathy, Ischemic; Postoperative Complications; Randomized Controlled Trials as Topic; Treatment Failure; Visual Acuity
PubMed: 25763979
DOI: 10.1002/14651858.CD001538.pub4 -
Acta Ophthalmologica Feb 2021The effectiveness and safety of surgery for spheno-orbital meningiomas remains subject of debate, as studies often describe different surgical approaches and... (Meta-Analysis)
Meta-Analysis
PURPOSE
The effectiveness and safety of surgery for spheno-orbital meningiomas remains subject of debate, as studies often describe different surgical approaches and reconstruction techniques with very heterogeneous outcomes. We aimed to systematically summarize and analyse the literature on spheno-orbital meningiomas regarding presenting symptoms, surgical techniques, outcomes and complications.
METHODS
Studies were retrieved from eight databases. Original articles were included if in ≥5 patients presenting symptoms, surgical treatment and outcomes were described. Fixed- and random-effects meta-analysis was performed to estimate weighted percentages with 95%CIs of presenting symptoms, outcomes and complications.
RESULTS
Thirty-eight articles were included describing 1486 patients. Proptosis was the most common presenting symptom (84%; 95%CI 76-91%), followed by unilateral visual acuity deficits (46%; 95%CI 40-51%) and visual field deficits (31%; 95%CI 20-43%). In 35/38 studies (92%), a pterional craniotomy was used. Decompression of the optic canal (82%) and the superior orbital fissure (66%) was most often performed, and usually dural (47%) and bony defects (76%) were reconstructed. In almost all patients, visual acuity (91%; 95%CI 86-96%), visual fields (87%; 95%CI 70-99%) and proptosis (96%; 95%CI 90-100%) improved. Furthermore, surgery showed improvement in 96% (95%CI 78-100%) for both diplopia and ophthalmoplegia. The most common surgical complications were hypesthesia (19%; 95%CI 10-30%), ptosis and diplopia (both 17%; 95%CI, respectively, 10-26% and 5-33%) and ophthalmoplegia (16%; 95%CI 10-24).
CONCLUSION
Patients with spheno-orbital meningioma usually present with proptosis or unilateral decreased visual acuity. Surgery shows to be effective in improving visual acuity and visual field deficits with mostly minor and well-tolerated complications.
Topics: Humans; Meningioma; Neurosurgical Procedures; Orbit; Orbital Neoplasms; Sphenoid Bone; Visual Acuity
PubMed: 32602264
DOI: 10.1111/aos.14517 -
The Cochrane Database of Systematic... Nov 2020Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical activity in the brain. Despite the development of more than 10 new antiepileptic drugs (AEDs) since the early 2000s, approximately a third of people with epilepsy remain resistant to pharmacotherapy, often requiring treatment with a combination of AEDs. In this review, we summarised the current evidence regarding rufinamide, a novel anticonvulsant medication, which, as a triazole derivative, is structurally unrelated to any other currently used anticonvulsant medication when used as an add-on treatment for drug-resistant epilepsy. In January 2009, rufinamide was approved by the US Food and Drug Administration for the treatment of children four years of age and older with Lennox-Gastaut syndrome. It is also approved as an add-on treatment for adults and adolescents with focal seizures. This is an updated version of the original Cochrane Review published in 2018.
OBJECTIVES
To evaluate the efficacy and tolerability of rufinamide when used as an add-on treatment for people with drug-resistant epilepsy.
SEARCH METHODS
We imposed no language restrictions. We contacted the manufacturers of rufinamide and authors in the field to identify any relevant unpublished studies.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled, add-on trials of rufinamide, recruiting people (of any age or gender) with drug-resistant epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: 50% or greater reduction in seizure frequency (primary outcome); seizure freedom; treatment withdrawal; and adverse effects (secondary outcomes). Primary analyses were intention-to-treat (ITT) and we presented summary risk ratios (RRs) with 95% confidence intervals (CIs). We evaluated dose response in regression models. We carried out a risk of bias assessment for each included study using the Cochrane 'Risk of bias' tool and assessed the overall certainty of evidence using the GRADE approach.
MAIN RESULTS
The review included six trials, representing 1759 participants. Four trials (1563 participants) included people with uncontrolled focal seizures. Two trials (196 participants) included individuals with established Lennox-Gastaut syndrome. Overall, the age of adults ranged from 18 to 80 years and the age of children ranged from 4 to 16 years. Baseline phases ranged from 28 to 56 days and double-blind phases from 84 to 96 days. Five of the six included trials described adequate methods of concealment of randomisation, and only three described adequate blinding. All analyses were by ITT. Overall, five studies were at low risk of bias and one had unclear risk of bias due to lack of reported information around study design. All trials were sponsored by the manufacturer of rufinamide and therefore were at high risk of funding bias. The overall RR for 50% or greater reduction in seizure frequency was 1.79 (95% CI 1.44 to 2.22; 6 randomised controlled trials (RCTs), 1759 participants; moderate-certainty evidence), indicating that rufinamide (plus conventional AED) was significantly more effective than placebo (plus conventional AED) in reducing seizure frequency by at least 50% when added to conventionally used AEDs in people with drug-resistant focal epilepsy. Data from only one study (73 participants) reported seizure freedom: RR 1.32 (95% CI 0.36 to 4.86; 1 RCT, 73 participants; moderate-certainty evidence). The overall RR for treatment withdrawal (for any reason and due to AED) was 1.83 (95% CI 1.45 to 2.31; 6 RCTs, 1759 participants; moderate-certainty evidence), showing that rufinamide was significantly more likely to be withdrawn than placebo. Most adverse effects were significantly more likely to occur in the rufinamide-treated group. Adverse events significantly associated with rufinamide were headache, dizziness, somnolence, vomiting, nausea, fatigue, and diplopia. The RRs for these adverse effects were as follows: headache 1.36 (95% Cl 1.08 to 1.69; 3 RCTs, 1228 participants; high-certainty evidence); dizziness 2.52 (95% Cl 1.90 to 3.34; 3 RCTs, 1295 participants; moderate-certainty evidence); somnolence 1.94 (95% Cl 1.44 to 2.61; 6 RCTs, 1759 participants; moderate-certainty evidence); vomiting 2.95 (95% Cl 1.80 to 4.82; 4 RCTs, 777 participants; low-certainty evidence); nausea 1.87 (95% Cl 1.33 to 2.64; 3 RCTs, 1295 participants; moderate-certainty evidence); fatigue 1.46 (95% Cl 1.08 to 1.97; 3 RCTs, 1295 participants; moderate-certainty evidence); and diplopia 4.60 (95% Cl 2.53 to 8.38; 3 RCTs, 1295 participants; low-certainty evidence). There was no important heterogeneity between studies for any outcomes. Overall, we assessed the evidence as moderate to low certainty due to wide CIs and potential risk of bias from some studies contributing to the analysis.
AUTHORS' CONCLUSIONS
For people with drug-resistant focal epilepsy, rufinamide when used as an add-on treatment was effective in reducing seizure frequency. However, the trials reviewed were of relatively short duration and provided no evidence for long-term use of rufinamide. In the short term, rufinamide as an add-on was associated with several adverse events. This review focused on the use of rufinamide in drug-resistant focal epilepsy, and the results cannot be generalised to add-on treatment for generalised epilepsies. Likewise, no inference can be made about the effects of rufinamide when used as monotherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Bias; Child; Child, Preschool; Drug Resistant Epilepsy; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Triazoles
PubMed: 33179247
DOI: 10.1002/14651858.CD011772.pub3