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JAMA Psychiatry Dec 2022Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Whether ketamine is as effective as electroconvulsive therapy (ECT) among patients with major depressive episode remains unknown.
OBJECTIVE
To systematically review and meta-analyze data about clinical efficacy and safety for ketamine and ECT in patients with major depressive episode.
DATA SOURCES
PubMed, MEDLINE, Cochrane Library, and Embase were systematically searched using Medical Subject Headings (MeSH) terms and text keywords from database inception through April 19, 2022, with no language limits. Two authors also manually and independently searched all relevant studies in US and European clinical trial registries and Google Scholar.
STUDY SELECTION
Included were studies that involved (1) a diagnosis of depression using standardized diagnostic criteria, (2) intervention/comparator groups consisting of ECT and ketamine, and (3) depressive symptoms as an efficacy outcome using standardized measures.
DATA EXTRACTION AND SYNTHESIS
Data extraction was completed independently by 2 extractors and cross-checked for errors. Hedges g standardized mean differences (SMDs) were used for improvement in depressive symptoms. SMDs with corresponding 95% CIs were estimated using fixed- or random-effects models. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed.
MAIN OUTCOMES AND MEASURES
Efficacy outcomes included depression severity, cognition, and memory performance. Safety outcomes included serious adverse events (eg, suicide attempts and deaths) and other adverse events.
RESULTS
Six clinical trials comprising 340 patients (n = 162 for ECT and n = 178 for ketamine) were included in the review. Six of 6 studies enrolled patients who were eligible to receive ECT, 6 studies were conducted in inpatient settings, and 5 studies were randomized clinical trials. The overall pooled SMD for depression symptoms for ECT when compared with ketamine was -0.69 (95% CI, -0.89 to -0.48; Cochran Q, P = .15; I2 = 39%), suggesting an efficacy advantage for ECT compared with ketamine for depression severity. Significant differences were not observed between groups for studies that assessed cognition/memory or serious adverse events. Both ketamine and ECT had unique adverse effect profiles (ie, ketamine: lower risks for headache and muscle pain; ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, and transient dissociative/depersonalization symptoms). Limitations included low to moderate methodological quality and underpowered study designs.
CONCLUSIONS AND RELEVANCE
Findings from this systematic review and meta-analysis suggest that ECT may be superior to ketamine for improving depression severity in the acute phase, but treatment options should be individualized and patient-centered.
Topics: Humans; Electroconvulsive Therapy; Ketamine; Depressive Disorder, Major; Suicide, Attempted; Randomized Controlled Trials as Topic
PubMed: 36260324
DOI: 10.1001/jamapsychiatry.2022.3352 -
The Cochrane Database of Systematic... Jun 2022Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on... (Review)
Review
BACKGROUND
Thyroid-associated ophthalmopathy (TAO) is the most frequent extrathyroidal manifestation of Graves' disease, affecting up to 50% of patients. It has a great impact on quality of life. Rituximab (RTX) is a human/murine chimeric monoclonal antibody that targets the CD20 receptor on B-lymphocytes. Preliminary work has shown that blocking this CD20 receptor with RTX may affect the clinical course of TAO by reducing inflammation and the degree of proptosis. OBJECTIVES: This review update, originally published in 2013, assesses the efficacy and safety of using RTX for the treatment of TAO.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2022, Issue 2), which contains the Cochrane Eyes and Vision Trials Register, Ovid MEDLINE, Ovid Embase, Latin American and Caribbean Health Science Information database (LILACS), the ISRCTN registry, clinicaltrials.gov and the WHO International Clinical Trials Registry Platform (WHO ICTRP). There were no language restrictions in the electronic search for trials. We last searched the electronic databases on 22 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of RTX administered by intravenous infusion using any dosage regimen for the treatment of active TAO in adults, compared to placebo or glucocorticoids treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently scanned titles and abstracts, and screened full-text reports of potentially relevant studies. The outcomes of interest in this review were: clinical activity score (CAS), NOSPECS severity scale, proptosis (mm), palpebral aperture (mm), extraocular motility (degrees or diplopia rating scale), quality of life and adverse effects.
MAIN RESULTS
We identified two studies that met the inclusion criteria in this updated review. Across both studies, the mean age of participants was 55 years and 77% were women. RTX compared to intravenous methylprednisolone (IVMP) One study, conducted in Italy, compared RTX (n = 15 after one participant withdrew) with IVMP (n = 16) for active TAO (CAS ≥ 3 out of 7 or 4 out of 10). We judged this study to be at low risk of bias in most domains, but it was stopped early because of disease reactivation in the comparator group (5/16 participants). This study provided low-certainty evidence that RTX may result in CAS improvement at 24 weeks compared to IVMP (15/15 versus 12/16 improved by ≥ 2 points; risk ratio (RR) 1.32, 95% confidence interval (CI) 0.98 to 1.78). Only very low-certainty evidence was available for the other outcomes: NOSPECS improvement by 2 or more classes (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); proptosis improvement by 2 mm or more (0/15 versus 1/16; RR 0.35, 95% CI 0.02 to 8.08); palpebral aperture improvement by 3 mm or more (2/15 versus 0/16; RR 5.31, 95% CI 0.28 to 102.38); motility improvement by 1 class or more (3/15 versus 3/16; RR 1.07, 95% CI 0.25 to 4.49); and improvement on the Graves' ophthalmopathy QoL scale by at least 6 points for "functioning" (5/14 versus 8/13; RR 0.58, 95% CI 0.25 to 1.32), and "appearance" (9/14 versus 6/13; RR 1.39, 95% CI 0.69 to 2.82). Adverse events were more common in the RTX group (RR 1.39, 95% CI 0.90 to 2.13; low-certainty evidence). Minor adverse effects (mild infusion reactions) were observed in most people receiving RTX at first infusion. Two participants experienced a major infusion reaction, likely cytokine release syndrome. RTX compared to placebo One study, conducted in the USA, enrolled 25 participants with active TAO (CAS ≥ 4 out of 7), comparing RTX (13 participants) to placebo. We judged this study to be at low risk of bias in most domains, but it was stopped early due to recruitment issues. It provided very low-certainty evidence on the following outcomes at 24 weeks: CAS improvement by 2 or more points (4/13 RTX versus 3/12 placebo; RR 1.23, 95% CI 0.34 to 4.40); NOSPECS improvement by 2 or more classes (2/13 versus 2/12; RR 0.92, 95% CI 0.15 to 5.56); proptosis improvement by 2 mm or more (2/13 versus 4/12; RR 0.46, 95% CI 0.10 to 2.08); palpebral aperture median change (0 mm in RTX group, in both eyes separately, versus -0.5 mm and 0.5 mm in placebo group right and left eye, respectively); motility median diplopia score (3 versus 2.5); SF-12 physical component median score (45.9 versus 40.3) and mental component median score (52.8 versus 46.1). More participants in the RTX group experienced adverse effects (8/13 versus 3/12; RR 2.46, 95% CI 0.84 to 7.18). AUTHORS' CONCLUSIONS: There is currently insufficient evidence to support the use of RTX in people with TAO. Future studies investigating RTX in people with active TAO may need to be multi-centre in order to recruit enough participants to make an adequate judgement on the efficacy and safety of this novel therapy.
Topics: Adult; Animals; Antibodies, Monoclonal; Diplopia; Female; Graves Ophthalmopathy; Humans; Male; Mice; Middle Aged; Rituximab
PubMed: 35709102
DOI: 10.1002/14651858.CD009226.pub3 -
Frontiers in Endocrinology 2023The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to... (Meta-Analysis)
Meta-Analysis
BACKGROUNDS
The effects of various treatments on Graves' ophthalmopathy (GO) have been studied. As monoclonal antibodies (mAbs) have been proposed for the treatment of moderate to severe GO, direct comparisons between different mAbs are lacking.We therefore conducted this meta-analysis to objectively compare the efficacy and safety of intravenous mAbs.
METHODS
To identify eligible trials, references published before September 2022 were electronically searched in PubMed, Web of Science, Pubmed, Embase,Cochrane Library, CBM, CNKI,Wan-Fang and ICTRP databases.The Newcastle-Ottawa scale (NOS) and the Cochrane Risk of Bias Assessment Tool were used to assess the risk of bias of the original studies.The primary and secondary outcomes were the response and inactivation rates, with the secondary outcomes being the clinical activity score (CAS),the improvement of proptosis and diplopia improvement,and the adverse event rate. Publication bias was evaluated, along with subgroup and sensitivity analyses.
RESULTS
A total of 12 trials with 448 patients were included. The meta-analysis showed that TCZ (tocilizumab) was most likely to be the best treatment in terms of response according to indirect contrast, followed by TMB (teprotumumab) and RTX (rituximab).TCZ, followed by TMB and RTX, was also most likely to be the best treatment in terms of reducing proptosis. In terms of improving diplopia, TMB was most likely to be the best treatment, followed by TCZ and RTX.TCZ was the highest probability of safety, followed by RTX and TMB.
CONCLUSIONS
Based on the best available evidence,TCZ should be the preferred treatment for moderate to severe GO.In the absence of head-to-head trials,indirect comparisons of treatments are routinely used to estimate the effectiveness of the treatments of interest. In addition,the optimal dose and potential mechanism of action of monoclonal antibodies remain to be established,and it is encouraging that the treatment paradigm for GO may change in the future.This study was designed in accordance with the Preferred Reporting Items for conducting Systematic Reviews and Meta-Analyses (PRISMA)(27).
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/prospero, identifier CRD42023398170.
Topics: Humans; Antibodies, Monoclonal; Immunoglobulins, Intravenous; Diplopia; Rituximab; Graves Ophthalmopathy; Exophthalmos
PubMed: 37288301
DOI: 10.3389/fendo.2023.1160936 -
BMJ Open Apr 2023To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the efficacy and safety of tube shunt implantation with trabeculectomy in the treatment of patients with glaucoma.
METHODS
A systematic literature search was performed for studies comparing tube with trabeculectomy in patients with glaucoma (final search date: 27 February 2022). Comparisons between tube and trabeculectomy were grouped by the type of tube (Ahmed, Baerveldt, Ex-PRESS and XEN). The primary endpoints included intraocular pressure (IOP), IOP reduction (IOPR), IOPR percentage (IOPR%), complete success rate (CSR), qualified success rate (QSR) and adverse events (AEs).
RESULTS
Forty-nine studies were included in this meta-analysis and presented data for 3795 eyes (Ahmed: 670, Baerveldt: 561, Ex-PRESS: 473, XEN: 199, trabeculectomy: 1892). Ahmed and Ex-PRESS were similar to trabeculectomy in terms of IOP outcomes and success rate (Ahmed vs trabeculectomy: IOPR%: mean difference (MD)=1.34 (-5.35, 8.02), p=0.69; Ex-PRESS vs trabeculectomy: IOPR%: MD=0.12 (-3.07, 3.31), p=0.94). The IOP outcomes for Baerveldt were worse than those for trabeculectomy (IOPR%: MD=-7.51 (-10.68, -4.35), p<0.00001), but the QSR was higher. No significant difference was shown for the CSR. XEN was worse than trabeculectomy in terms of IOP outcomes (IOPR%: MD=-7.87 (-13.55, -2.18), p=0.007), while the success rate was similar. Ahmed and Ex-PRESS had a lower incidence of AEs than trabeculectomy. Baerveldt had a lower incidence of bleb leakage/wound leakage, hyphaema and hypotonic maculopathy than trabeculectomy but a higher incidence of concurrent cataracts, diplopia/strabismus and tube erosion. The incidence of AEs was similar for the XEN and trabeculectomy procedures.
CONCLUSION
Compared with trabeculectomy, both Ahmed and Ex-PRESS appear to be associated with similar ocular hypotensive effects and lower incidences of AEs. However, Baerveldt and XEN cannot achieve sufficient reductions in IOP outcomes similar to those of trabeculectomy.
PROSPERO REGISTRATION NUMBER
CRD42021257852.
Topics: Humans; Trabeculectomy; Glaucoma Drainage Implants; Treatment Outcome; Glaucoma; Intraocular Pressure
PubMed: 37080625
DOI: 10.1136/bmjopen-2022-065921 -
The Cochrane Database of Systematic... Oct 2017This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good prognosis, but up to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the Cochrane Review published in the Cochrane Library 2011, Issue 12.The majority of people with epilepsy have a good prognosis, but up to 30% of people continue to have seizures despite several regimens of antiepileptic drugs. In this review, we summarized the current evidence regarding eslicarbazepine acetate (ESL) when used as an add-on treatment for drug-resistant partial epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant partial epilepsy.
SEARCH METHODS
The searches for the original review were run in November 2011. Subsequently, we searched the Cochrane Epilepsy Group Specialized Register (6 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11) and MEDLINE (1946 to 6 December 2016). There were no language restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of ESL and experts in the field for information about any unpublished or ongoing studies.
SELECTION CRITERIA
Randomized placebo controlled double-blind add-on trials of ESL in people with drug-resistant partial epilepsy.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects, and drug interactions. Primary analyses were by intention to treat (ITT). The dose-response relationship was evaluated in regression models.
MAIN RESULTS
We included five trials (1799 participants) rated at low risk of bias; all studies were funded by BIAL. The overall risk ratio (RR) with 95% confidence interval (CI) for 50% or greater reduction in seizure frequency was 1.71 (95% CI 1.42 to 2.05). Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. ESL was significantly associated with seizure freedom (RR 2.90, 95% CI 1.49 to 5.68). Participants were more likely to have ESL withdrawn for adverse effects (RR 2.66, 95% CI 1.42 to 4.96) but not for any reason (RR 1.19, 95% CI 0.86 to 1.64). The following adverse effects were significantly associated with ESL: dizziness (RR 2.81, 99% CI 1.86 to 4.27); nausea (RR 2.61, 99% CI 1.36 to 5.01); diplopia (RR 4.14, 99% CI 1.74 to 9.84); somnolence (RR 1.71, 99% CI 1.11 to 2.63) and vomiting (RR 3.30, 99% CI 1.34 to 8.13). Overall the quality of the evidence was rated as moderate to high.
AUTHORS' CONCLUSIONS
ESL reduces seizure frequency when used as an add-on treatment for people with drug-resistant partial epilepsy. The trials included in this review were of short-term duration and focused on adults. One new trial has been included in this update, but the conclusions are unchanged.
Topics: Adult; Aged; Anticonvulsants; Dibenzazepines; Drug Resistance; Drug Therapy, Combination; Epilepsies, Partial; Humans; Middle Aged; Randomized Controlled Trials as Topic; Young Adult
PubMed: 29067682
DOI: 10.1002/14651858.CD008907.pub3 -
Journal of Personalized Medicine Feb 2024Although the reported frequency of diplopia is between 10 to 40% of patients with Parkinson's disease (PD) and other movement disorders, it remains one of the most... (Review)
Review
INTRODUCTION
Although the reported frequency of diplopia is between 10 to 40% of patients with Parkinson's disease (PD) and other movement disorders, it remains one of the most undiagnosed non-motor symptoms. Furthermore, it has a major impact on the quality of life of these patients. The aim of this study is to systematically review the literature regarding the frequency, causes, and implications of diplopia in movement disorders.
METHODOLOGY
An electronic search was conducted in March and June 2023 using the PubMed database in order to identify appropriate studies. Studies that were written in English, that represented observational, analytical studies, and case reports, and that provided information regarding diplopia in movement disorders were included in the systematic review.
RESULTS
A total of 686 articles were identified out of which 43 met the inclusion criteria. The studies included in the systematic review ranged from descriptive studies (case reports and case series) to analytical-observational studies (cross-sectional studies, prospective and retrospective cohort studies, and case-control studies). In Parkinson's disease, the incidence of diplopia ranged from 10 to 38%. In these patients, diplopia was linked to the presence of visual hallucinations and cognitive decline but also to convergence insufficiency and the presence of motor fluctuations. Cases of diplopia secondary to deep brain stimulation were also reported. Diplopia was associated with longer disease duration and worse motor and non-motor scores. Diplopia was also reported in other movement disorders such as multiple system atrophy (frequency as high as 18%) and progressive supranuclear palsy (frequency as high as 39%) and was associated with increased mortality and shorter duration in life span.
CONCLUSIONS
Diplopia occurs in up to 38% of patients with movement disorders and has a negative impact on their health-related quality of life. Treating physicians should actively ask about diplopia and other ophthalmological symptoms, as many patients do not spontaneously report them. The pathophysiology of diplopia is complex, and it involves heterogeneous peripheral and central mechanisms. The management of these patients should involve a multidisciplinary team of health professionals in order to provide appropriate, tailored management.
PubMed: 38541012
DOI: 10.3390/jpm14030270 -
Journal of Affective Disorders Apr 2024Ketamine and esketamine has been suggested to have potential efficacy in preventing postpartum depression (PPD) recent years. The aim of this meta-analysis was to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ketamine and esketamine has been suggested to have potential efficacy in preventing postpartum depression (PPD) recent years. The aim of this meta-analysis was to evaluate the effectiveness of ketamine and esketamine on PPD after cesarean delivery.
METHODS
We systematically searched PubMed, Embase, and the Cochrane Library for studies investigating the efficacy of ketamine and esketamine in preventing PPD. The primary outcomes of this study were risk ratios (RRs) and EPDS scores (Edinburgh Postnatal Depression Scale) in relation to PPD after ketamine and esketamine. The second outcomes were the postoperative adverse events.
RESULTS
Thirteen randomized controlled trials (RCTs) and one retrospective study including 2916 patients were analyzed, including six on the use of ketamine and eight on the use of esketamine. The risk ratios and EPDS scores of PPD were significantly decreased in the ketamine/esketamine group compared to those in the control group in one week and four weeks postoperative periods. Subgroup analyses showed that high dosage, administrated in patient controlled intravenous analgesia (PCIA) method and only esketamine exhibited a significant reduction in the incidence and EPDS scores of PPD in one week and four week postoperative. However, the incidences of postoperative adverse events, such as dizziness, diplopia, hallucination, and headache were significantly higher in the ketamine/esketamine group than that in the control group.
CONCLUSION
Ketamine and esketamine appear to be effective in preventing PPD in the one week and four week postoperative periods after cesarean delivery with moderate certainty of evidence. But they can also lead to some short-term complications too. Future high-quality studies are needed to confirm the efficacy of ketamine and esketamine in different countries.
Topics: Female; Pregnancy; Humans; Ketamine; Depression, Postpartum; Cesarean Section; Headache; Randomized Controlled Trials as Topic
PubMed: 38286233
DOI: 10.1016/j.jad.2024.01.202 -
Journal of Neuro-oncology Jun 2021We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced... (Review)
Review
PURPOSE
We aim to systematically review and summarize the demographics, clinical features, management strategies, and clinical outcomes of primary and radiation-induced skull-base osteosarcoma (SBO).
METHODS
PubMed, Scopus, and Cochrane databases were used to identify relevant articles. Papers including SBO cases and sufficient clinical outcome data were included. A comprehensive clinical characteristic review and survival analysis were also conducted.
RESULTS
Forty-one studies describing 67 patients were included. The median age was 31 years (male = 59.7%). The middle skull-base was most commonly involved (52.7%), followed by anterior (34.5%) and posterior (12.7%) skull-base. Headache (27%), exophthalmos (18%), and diplopia (10%) were common presenting symptoms. Sixty-eight percent of patients had primary SBO, while 25% had radiation-induced SBO. Surgery was the main treatment modality in 89% of cases. Chemotherapy was administered in 65.7% and radiotherapy in 50%. Median progression-free survival (PFS) was 12 months, and the overall 5-year survival was 22%. The five-year survival rates of radiation-induced SBO and primary SBO were 39% and 16%, respectively (P < 0.05).
CONCLUSION
SBO is a malignant disease with poor survival outcomes. Surgical resection is the primary management modality, in conjunction with chemotherapy and radiotherapy. Radiation-induced SBO has a superior survival outcome as compared to its primary counterpart. Complete surgical resection showed a statistically insignificant survival benefit as compared to partial resection.
Topics: Humans; Osteosarcoma; Progression-Free Survival; Skull Base; Skull Base Neoplasms; Treatment Outcome
PubMed: 33999382
DOI: 10.1007/s11060-021-03757-z -
Eye (London, England) Mar 2018PurposeTo determine the safety and effectiveness of orbital decompression for thyroid eye disease (TED) in our unit. To put this in the context of previously published... (Review)
Review
PurposeTo determine the safety and effectiveness of orbital decompression for thyroid eye disease (TED) in our unit. To put this in the context of previously published literature.Patients and methodsA retrospective case review of all patients undergoing orbital decompression for TED under the care of one orbital surgeon (SMS) between January 2009 and December 2015. A systematic literature review of orbital decompression for TED.ResultsWithin the reviewed period, 93 orbits of 55 patients underwent decompression surgery for TED. There were 61 lateral (single) wall decompressions, 17 medial one-and-a-half wall, 11 two-and-a-half wall, 2 balanced two wall, and 2 orbital fat only decompressions. For the lateral (single) wall decompressions, mean reduction in exophthalmometry (95% confidence interval (CI) was 4.2 mm (3.7-4.8), for the medial one-and-a-half walls it was 2.9 mm (2.1-3.7), and for the two-and-a-half walls it was 7.6 mm (5.8-9.4). The most common complications were temporary postoperative numbness (29% of lateral decompressions, 17% of other bony decompressions, OR 0.50, 95% CI 0.12-2.11) and new postoperative diplopia (9% of lateral decompressions, 39% of other bony decompressions, OR 6.8, 95% CI 1. 5-30.9). Systematic literature searching showed reduction in exophthalmometry for lateral wall surgery of 3.6-4.8 mm, with new diplopia 0-38% and postoperative numbness 12-50%. For other bony decompressions, reduction in exophthalmometry was 2.5-8.0 mm with new diplopia 0-45% and postoperative numbness up to 52%.ConclusionDiffering approaches to orbital decompression exist. If the correct type of surgery is chosen, then safe, adequate surgical outcomes can be achieved.
Topics: Adult; Aged; Decompression, Surgical; Drainage; Female; Graves Ophthalmopathy; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies
PubMed: 29243735
DOI: 10.1038/eye.2017.260 -
The Cochrane Database of Systematic... Apr 2018Epilepsy is a central nervous system disorder (neurological disorder). Epileptic seizures are the result of excessive and abnormal cortical nerve cell electrical... (Review)
Review
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 refractory epilepsy. In January 2009, rufinamide was approved by the US Food and Drug Administration for 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.
OBJECTIVES
To evaluate the efficacy and tolerability of rufinamide when used as an add-on treatment in people with refractory epilepsy.
SEARCH METHODS
On 2 October 2017, we searched the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO), MEDLINE (Ovid, 1946), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We also 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 refractory 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 outcomes); seizure freedom; treatment withdrawal; and adverse effects (secondary outcomes). Primary analyses were intention-to-treat (ITT) and we presented summary risk ratios (RR) with 95% confidence intervals (CI). 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 quality of evidence using the GRADE approach, which we presented in a 'Summary of findings' table.
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 established Lennox-Gastaut syndrome. Overall, the age of the adults ranged from 18 to 80 years and the age of the infants ranged from four to 16 years. Baseline phase 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 RCTs; moderate-quality 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 refractory focal epilepsy. 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; moderate-quality evidence) showing that rufinamide was significantly more likely to be withdrawn than placebo. In respect of adverse effects, most were significantly more likely to occur in the rufinamide-treated group. The adverse events significantly associated with rufinamide were: headache, dizziness, somnolence, vomiting, nausea, fatigue and diplopia. The RRs of these adverse effects were: headache 1.36 (95% Cl 1.08 to 1.69; 3 RCTs; high-quality evidence); dizziness 2.52 (95% Cl 1.90 to 3.34; 3 RCTs; moderate-quality evidence); somnolence 1.94 (95% Cl 1.44 to 2.61; 6 RCTs; moderate-quality evidence); vomiting 2.95 (95% Cl 1.80 to 4.82; 4 RCTs; low-quality evidence); nausea 1.87 (95% Cl 1.33 to 2.64; 3 RCTs; moderate-quality evidence); fatigue 1.46 (95% Cl 1.08 to 1.97; 3 RCTs; moderate-quality evidence); and diplopia 4.60 (95% Cl 2.53 to 8.38; 3 RCTs; low-quality evidence). There was no important heterogeneity between studies for any of the outcomes. Overall, we assessed the evidence as moderate to low quality, due to potential risk of bias from some studies contributing to the analysis and wide CIs.
AUTHORS' CONCLUSIONS
In 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 the 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; Child; Child, Preschool; Drug Resistant Epilepsy; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Triazoles
PubMed: 29691835
DOI: 10.1002/14651858.CD011772.pub2