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Medicine Sep 2016The aim of this systematic review was to update, complete, and critically evaluate the evidence from placebo-controlled randomized clinical trials (RCTs) of ginseng for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this systematic review was to update, complete, and critically evaluate the evidence from placebo-controlled randomized clinical trials (RCTs) of ginseng for managing menopausal women's health.
METHODS
We searched the literature using 13 databases (MEDLINE, AMED, EMBASE, the Cochrane Library, 6 Korean Medical, and 3 Chinese Databases) from their inception to July 2016 and included all double-blind RCTs that compared any type of ginseng with a placebo control in postmenopausal women. The methodological quality of all studies was assessed using a Cochrane risk of bias tool.
RESULTS
Ten RCTs met our inclusion criteria. Most RCTs had unclear risk of bias. One RCT did not show a significant difference in hot flash frequency between Korean red ginseng (KRG) and placebo. The second RCT reported positive effects of KRG on menopausal symptoms. The third RCT found beneficial effects of ginseng (Ginsena) on depression, well-being, and general health. Four RCTs failed to show significant differences in various hormones between KRG and placebo controls except dehydroepiandrosterone. Two other RCTs failed to show effects of KRG on endometrial thickness in menopausal women. The other RCT also failed to show the effects of American ginseng on oxidative stress markers and other antioxidant enzymes.
CONCLUSION
Our systematic review provided positive evidence of ginseng for sexual function and KRG for sexual arousal and total hot flashes score in menopausal women. However, the results of KRG or ginseng failed to show specific effects on hot flash frequency, hormones, biomarkers, or endometrial thickness. The level of evidence for these findings was low because of unclear risk of bias.
Topics: Complementary Therapies; Double-Blind Method; Female; Humans; Menopause; Panax; Phytotherapy; Plant Extracts; Quality of Life; Randomized Controlled Trials as Topic; Treatment Outcome; Women's Health
PubMed: 27661038
DOI: 10.1097/MD.0000000000004914 -
The Cochrane Database of Systematic... Aug 2013Heparin as an adjunct in assisted reproduction (peri-implantation heparin) is given at or after egg collection or at embryo transfer during assisted reproduction.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heparin as an adjunct in assisted reproduction (peri-implantation heparin) is given at or after egg collection or at embryo transfer during assisted reproduction. Heparin has been advocated to improve embryo implantation and clinical outcomes. It has been proposed that heparin enhances the intra-uterine environment by improving decidualisation with an associated activation of growth factors and a cytokine expression profile in the endometrium that is favourable to pregnancy.
OBJECTIVES
To investigate whether the administration of heparin around the time of implantation (peri-implantation heparin) improves clinical outcomes in subfertile women undergoing assisted reproduction.
SEARCH METHODS
A comprehensive and exhaustive search strategy was developed in consultation with the Trials Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group (MDSG). The strategy was used in an attempt to identify all relevant studies regardless of language or publication status (published, unpublished, in press, and in progress). Relevant trials were identified from both electronic databases and other resources (last search 6 May 2013).
SELECTION CRITERIA
All randomised controlled trials (RCTs) were included where peri-implantation heparin was given during assisted reproduction. Peri-implantation low molecular weight heparin (LMWH) during IVF/ICSI was given at or after egg collection or at embryo transfer in the included studies. Live birth rate was the primary outcome.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and quality of trials and extracted relevant data. The quality of the evidence was evaluated using GRADE methods.
MAIN RESULTS
Three RCTs (involving 386 women) were included in the review.Peri-implantation LMWH administration during assisted reproduction was associated with a significant improvement in live birth rate compared with placebo or no LMWH (odds ratio (OR) 1.77, 95% confidence interval (CI) 1.07 to 2.90, three studies, 386 women, I(2) = 51%, very low quality evidence with high heterogeneity). There was also a significant improvement in the clinical pregnancy rate with use of LMWH (OR 1.61, 95% CI 1.03 to 2.53, three studies, 386 women, I(2) = 29%, very low quality evidence with low heterogeneity).However these findings should be interpreted with extreme caution as they were dependent upon the choice of statistical method: they were no longer statistically significant when a random-effects model was used.Adverse events were poorly reported in all included studies, with no comparative data available. However, LMWH did cause adverse effects including bruising, ecchymosis, bleeding, thrombocytopenia and allergic reactions. It appeared that these adverse effects were increased if heparin therapy was used over a longer duration.
AUTHORS' CONCLUSIONS
The results of this Cochrane review of three randomised controlled trials with a total of 386 women suggested that peri-implantation LMWH in assisted reproduction treatment (ART) cycles may improve the live birth rate in women undergoing assisted reproduction. However, these results were dependent on small low quality studies with substantial heterogeneity, and were sensitive to the choice of statistical model. There were side effects reported with use of heparin, including bruising and bleeding, and no reliable data on long-term effects. The results do not justify this use of heparin outside well-conducted research trials.These findings need to be further investigated with well-designed, adequately powered, double-blind, randomised, placebo-controlled, multicentre trials. Further investigations could also focus on the effects of the local (uterine) and not systemic application of heparin during ART.
Topics: Anticoagulants; Birth Rate; Drug Administration Schedule; Embryo Implantation; Embryo Transfer; Female; Heparin, Low-Molecular-Weight; Humans; Live Birth; Pregnancy; Randomized Controlled Trials as Topic; Reproductive Techniques, Assisted
PubMed: 23955506
DOI: 10.1002/14651858.CD009452.pub2 -
Trials Mar 2017There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its... (Review)
Review
BACKGROUND
There is no consensus on the preferred method for defining the non-inferiority margin in non-inferiority trials, and previous studies showed that the rationale for its choice is often not reported. This study investigated how the non-inferiority margin is defined in the published literature, and whether its reporting has changed over time.
METHODS
A systematic PubMed search was conducted for all published randomized, double-blind, non-inferiority trials from January 1, 1966, to February 6, 2015. The primary outcome was the number of margins that were defined by methods other than the historical evidence of the active comparator. This was evaluated for a time trend. We also assessed the under-reporting of the methods of defining the margin as a secondary outcome, and whether this changed over time. Both outcomes were analyzed using a Poisson log-linear model. Predictors for better reporting of the methods, and the use of the fixed-margin method (one of the historical evidence methods) were also analyzed using logistic regression.
RESULTS
Two hundred seventy-three articles were included, which account for 273 non-inferiority margins. There was no statistically significant difference in the number of margins that were defined by other methods compared to those defined based on the historical evidence (ratio 2.17, 95% CI 0.86 to 5.82, p = 0.11), and this did not change over time. The number of margins for which methods were unreported was similar to those with reported methods (ratio 1.35, 95% CI 0.76 to 2.43, p = 0.31), with no change over time. The method of defining the margin was less often reported in journals with low-impact factors compared to journals with high-impact factors (OR 0.20; 95% CI 0.10 to 0.37, p < 0.0001). The publication of the FDA draft guidance in 2010 was associated with increased reporting of the fixed-margin method (after versus before 2010) (OR 3.54; 95% CI 1.12 to 13.35, p = 0.04).
CONCLUSIONS
Non-inferiority margins are not commonly defined based on the historical evidence of the active comparator, and they are poorly reported. Authors, reviewers, and editors need to take notice of reporting this critical information to allow for better judgment of non-inferiority trials.
Topics: Data Interpretation, Statistical; Double-Blind Method; Equivalence Trials as Topic; Humans; Models, Statistical; Randomized Controlled Trials as Topic; Research Design
PubMed: 28270184
DOI: 10.1186/s13063-017-1859-x -
Journal of Behavioral Addictions Oct 2023Compulsive buying-shopping disorder (CBSD) is mentioned as an example of other specified impulse control disorders in the ICD-11 coding tool, highlighting its clinical... (Review)
Review
BACKGROUND AND AIMS
Compulsive buying-shopping disorder (CBSD) is mentioned as an example of other specified impulse control disorders in the ICD-11 coding tool, highlighting its clinical relevance and need for treatment. The aim of the present work was to provide a systematic update on treatment studies for CBSD, with a particular focus on online CBSD.
METHOD
The preregistered systematic review (PROSPERO, CRD42021257379) was performed in accordance with the PRISMA 2020 statement. A literature search was conducted using the PubMed, Scopus, Web of Science and PsycInfo databases. Original research published between January 2000 and December 2022 was included. Risk of reporting bias was evaluated with the CONSORT guideline for randomized controlled trials. Effect sizes for primary CBSD outcomes were calculated.
RESULTS
Thirteen studies were included (psychotherapy: 2 open, 4 waitlist control design; medication: 2 open, 3 placebo-controlled, 2 open-label phase followed by a double-blind discontinuation phase; participants treatment/control 349/149). None of the studies addressed online CBSD. Psychotherapy studies suggest that group cognitive-behavioral therapy is effective in reducing CBSD symptoms. Pharmacological studies with selective serotonin re-uptake inhibitors or topiramate did not indicate superiority over placebo. Predictors of treatment outcome were rarely examined, mechanisms of change were not studied at all. Risk of reporting bias was high in most studies.
DISCUSSION
Poor methodological and low quality of reporting of included studies reduce the reliability of conclusions. There is a lack of studies targeting online CBSD. More high-quality treatment research is needed with more emphasis on the CBSD subtype and mechanisms of change.
Topics: Humans; Reproducibility of Results; Compulsive Behavior; Compulsive Personality Disorder; Disruptive, Impulse Control, and Conduct Disorders; Psychotherapy; Randomized Controlled Trials as Topic
PubMed: 37450373
DOI: 10.1556/2006.2023.00033 -
The British Journal of Psychiatry : the... Jan 2011Depression is a common condition that has been frequently treated with psychotropics. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is a common condition that has been frequently treated with psychotropics.
AIMS
To review systematically the evidence of efficacy and acceptability of antidepressant and benzodiazepine treatments for patients with minor depression.
METHOD
A systematic review and meta-analysis of double-blind randomised controlled trials comparing antidepressants or benzodiazepines v. placebo in adults with minor depression. Data were obtained from MEDLINE, CINAHL, EMBASE, PsycInfo, Cochrane Controlled Trials Register and pharmaceutical company websites. Risk of bias was assessed for the generation of the allocation sequence, allocation concealment, masking, incomplete outcome data, and sponsorship bias.
RESULTS
Six studies met inclusion criteria. Three studies compared paroxetine with placebo; fluoxetine, amitriptyline and isocarboxazid were studied in one study each. No studies compared benzodiazepines with placebo. In terms of failures to respond to treatment (6 studies, 234 patients treated with antidepressants and 234 with placebo) no significant difference between antidepressants and placebo was found (relative risk (RR) 0.94, 95% CI 0.81-1.08). In terms of acceptability, data extracted from two studies (93 patients treated with antidepressants and 93 with placebo) showed no statistically significant difference between antidepressants and placebo (RR=1.06, 95% CI 0.65-1.73). There was no statistically significant between-study heterogeneity for any of the reported analyses.
CONCLUSIONS
There is evidence showing there is unlikely to be a clinically important advantage for antidepressants over placebo in individuals with minor depression. For benzodiazepines, no evidence is available, and thus it is not possible to determine their potential therapeutic role in this condition.
Topics: Adolescent; Adult; Antidepressive Agents; Benzodiazepines; Data Interpretation, Statistical; Depression; Double-Blind Method; Female; Humans; Male; Outcome Assessment, Health Care; Placebos; Randomized Controlled Trials as Topic
PubMed: 21200071
DOI: 10.1192/bjp.bp.109.076448 -
International Journal of Molecular... Dec 2022Althoughanti-inflammatory drug therapy has been identified as potentially beneficial for patients suffering from chronic subdural hematoma (cSDH), contemporary... (Meta-Analysis)
Meta-Analysis Review
Althoughanti-inflammatory drug therapy has been identified as potentially beneficial for patients suffering from chronic subdural hematoma (cSDH), contemporary literature presents contradictory results. In this meta-analysis, we aimed to investigate the impact of anti-inflammatory drug therapy on mortality and outcome. We searched for eligible randomized, placebo-controlled prospective trials (RTCs) on PubMed, Embase and Medline until July 2022. From 97 initially identified articles, five RTCs met the criteria and were included in our meta-analysis. Our results illustrate significantly lower rates of recurrent cSDH (OR: 0.35; 95% CI: 0.21-0.58, = 0.0001) in patients undergoing anti-inflammatory therapy. In the subgroup of patients undergoing primary conservative treatment, anti-inflammatory therapy was associated with lower rates of "switch to surgery" cases (OR: 0.30; 95% CI: 0.14-0.63, = 0.002). Despite these findings, anti-inflammatory drugs seemed to be associated with higher mortality rates in patients undergoing surgery (OR: 1.76; 95% CI: 1.03-3.01, = 0.04), although in the case of primary conservative treatment, no effect on mortality has been observed (OR: 2.45; 95% CI: 0.35-17.15, = 0.37). Further multicentric prospective randomized trials are needed to evaluate anti-inflammatory drugs as potentially suitable therapy for asymptomatic patients with cSDH to avoid the necessity of surgical hematoma evacuation on what are predominantly elderly, vulnerable, patients.
Topics: Humans; Aged; Hematoma, Subdural, Chronic; Prospective Studies; Double-Blind Method; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 36555838
DOI: 10.3390/ijms232416198 -
The Cochrane Database of Systematic... Aug 2017Malignant wounds are a devastating complication of cancer. They usually develop in the last six months of life, in the breast, chest wall or head and neck regions. They... (Review)
Review
BACKGROUND
Malignant wounds are a devastating complication of cancer. They usually develop in the last six months of life, in the breast, chest wall or head and neck regions. They are very difficult to treat successfully, and the commonly associated symptoms of pain, exudate, malodour, and the risk of haemorrhage are extremely distressing for those with advanced cancer. Treatment and care of malignant wounds is primarily palliative, and focuses on alleviating pain, controlling infection and odour from the wound, managing exudate and protecting the surrounding skin from further deterioration. In malignant wounds, with tissue degradation and death, there is proliferation of both anaerobic and aerobic bacteria. The aim of antibiotic therapy is to successfully eliminate these bacteria, reduce associated symptoms, such as odour, and promote wound healing.
OBJECTIVES
To assess the effects of systemic antibiotics for treating malignant wounds.
SEARCH METHODS
We searched the following electronic databases on 8 March 2017: the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library, 2017, Issue 3), Ovid MEDLINE, Ovid Embase and EBSCO CINAHL Plus. We also searched the clinical trial registries of the World Health Organization (WHO) International Clinical Trials Registry Platform (apps.who.int/trialsearch) and ClinicalTrials.gov on 20 March 2017; and OpenSIGLE (to identify grey literature) and ProQuest Dissertations & Theses Global (to retrieve dissertation theses related to our topic of interest) on 13 March 2017.
SELECTION CRITERIA
Randomised controlled trials that assessed the effects of any systemic antibiotics on malignant wounds were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened and selected trials for inclusion, assessed risk of bias and extracted study data. A third reviewer checked extracted data for accuracy prior to analysis.
MAIN RESULTS
We identified only one study for inclusion in this review. This study was a prospective, double-blind cross-over trial that compared the effect of systemic metronidazole with a placebo on odour in malignant wounds. Nine participants with a fungating wound and for whom the smell was troublesome were recruited and six of these completed both the intervention and control (placebo) stages of the trial. Each stage lasted fourteen days, with a fourteen day gap (washout period) between administration of the metronidazole and the placebo.The study, in comparing metronidazole and placebo, reported on two of this review's pre-specified primary outcomes (malodour and adverse effects of the treatment) and on none of the review's pre-specified secondary outcomes.MalodourThe mean malodour (smell) scores for the metronidazole group was 1.17 (standard deviation (SD) 1.60) and the mean for the placebo group was 3.33 (SD 0.82). It is unclear if systemic antibiotics were associated with a difference in malodour (1 study with 6 participants; MD -2.16, 95% CI -3.6 to -0.72) as the quality of the evidence (GRADE) was very low for this outcome. The study was downgraded due to high risk of attrition bias (33% loss to follow-up) and very serious imprecision due to the small sample size.Adverse effectsNo adverse effects of the treatment were reported in either the intervention or control group by the trial authors.
AUTHORS' CONCLUSIONS
It is uncertain whether systemic metronidazole leads to a reduction in malodour in patients with malignant wounds. This is because we were only able to include a single study at high risk of bias with a very small sample size, which focused only on patients with breast cancer. More research is needed to substantiate these findings and to investigate the effects of systemic metronidazole and other antibiotics on quality of life, pain relief, exudate and tumour containment in patients with malignant wounds.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Double-Blind Method; Humans; Metronidazole; Neoplasms; Odorants; Prospective Studies; Soft Tissue Injuries; Wounds and Injuries
PubMed: 28837757
DOI: 10.1002/14651858.CD011609.pub2 -
Advances in Therapy Jul 2023Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC).... (Review)
Review
INTRODUCTION
Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
METHODS
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
RESULTS
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
CONCLUSION
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
Topics: Humans; Eosinophils; Anti-Asthmatic Agents; Biological Products; Asthma; Leukocyte Count; Eosinophilia; Double-Blind Method
PubMed: 37233876
DOI: 10.1007/s12325-023-02514-0 -
The Cochrane Database of Systematic... Oct 2006Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.
OBJECTIVES
To assess the beneficial and harmful effects of anabolic-androgenic steroids for patients with alcoholic liver disease based on the results of randomised clinical trials.
SEARCH STRATEGY
We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Controlled Trials Register in The Cochrane Library, MEDLINE, EMBASE, LILACS, and Science Citation Index Expanded until June 2006. Electronic searches were combined with full text searches. Manufacturers and researchers in the field were also contacted.
SELECTION CRITERIA
Randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis, and/or alcoholic cirrhosis were included. Interventions encompassed anabolic-androgenic steroids at any dose or duration versus placebo or no intervention. The trials could be double blind, single blind, or unblinded. The trials could be unpublished or published, and no language limitations were applied.
DATA COLLECTION AND ANALYSIS
Outcomes are assessed at maximal follow-up. All analyses were performed according to the intention-to-treat method. The statistical package RevMan Analyses was used. The methodological quality of the randomised clinical trials was assessed.
MAIN RESULTS
Combining the results of five randomised clinical trials randomising 499 patients with alcoholic hepatitis and/or cirrhosis demonstrated no significant effects of anabolic-androgenic steroids on mortality (relative risk (RR) 1.01, 95% confidence interval (CI) 0.79 to 1.29), liver-related mortality (RR 0.83, 95% CI 0.60 to 1.15), complications of liver disease (RR 1.25, 95% CI 0.74 to 2.10), and liver histology. Anabolic-androgenic steroids did not significantly affect a number of other outcome measures, including sexual function and liver biochemistry. Anabolic-androgenic steroids were not associated with a significantly increased risk of non-serious adverse events (RR 1.14, 95% CI 0.50 to 2.59) or with serious adverse events (RR 4.54, 95% CI 0.57 to 36.30).
AUTHORS' CONCLUSIONS
This systematic review could not demonstrate any significant beneficial effects of anabolic-androgenic steroids on any clinically important outcomes (mortality, liver-related mortality, liver complications, and histology) of patients with alcoholic liver disease.
Topics: Anabolic Agents; Androgens; Humans; Liver Diseases, Alcoholic; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 17054157
DOI: 10.1002/14651858.CD003045.pub2 -
The Cochrane Database of Systematic... Aug 2022This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder,... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review first published in 2011, and most recently updated in 2019. Epilepsy is a chronic and disabling neurological disorder, affecting approximately 1% of the population. Up to 30% of people with epilepsy have seizures that are resistant to currently available antiepileptic drugs and require treatment with multiple antiepileptic drugs in combination. Felbamate is a second-generation antiepileptic drug that can be used as add-on therapy to standard antiepileptic drugs.
OBJECTIVES
To evaluate the efficacy and tolerability of felbamate versus placebo when used as an add-on treatment for people with drug-resistant focal-onset epilepsy.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 13 July 2021) on 15 July 2021. There were no language or time restrictions. We reviewed the reference lists of retrieved studies to search for additional reports of relevant studies. We also contacted the manufacturers of felbamate and experts in the field for information about any unpublished or ongoing studies.
SELECTION CRITERIA
We searched for randomised placebo-controlled add-on studies of people of any age with drug-resistant focal seizures. The studies could be double-blind, single-blind or unblinded and could be of parallel-group or cross-over design.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion and extracted information. In the case of disagreements, a third review author arbitrated. Review authors assessed the following outcomes: 50% or greater reduction in seizure frequency; absolute or percentage reduction in seizure frequency; treatment withdrawal; adverse effects; quality of life.
MAIN RESULTS
We included four randomised controlled trials, representing a total of 236 participants, in the review. Two trials had parallel-group design, the third had a two-period cross-over design, and the fourth had a three-period cross-over design. We judged all four studies to be at an unclear risk of bias overall. Bias arose from the incomplete reporting of methodological details, the incomplete and selective reporting of outcome data, and from participants having unstable drug regimens during experimental treatment in one trial. Due to significant methodological heterogeneity, clinical heterogeneity and differences in outcome measures, it was not possible to perform a meta-analysis of the extracted data. Only one study reported the outcome of 50% or greater reduction in seizure frequency, whilst three studies reported percentage reduction in seizure frequency compared to placebo. One study claimed an average seizure reduction of 35.8% with add-on felbamate whilst another study claimed a more modest reduction of 4.2%. Both studies reported that seizure frequency increased with add-on placebo and that there was a significant difference in seizure reduction between felbamate and placebo (P = 0.0005 and P = 0.018, respectively). The third study reported a 14% reduction in seizure frequency with add-on felbamate but stated that the difference between treatments was not significant. There were conflicting results regarding treatment withdrawal. One study reported a higher treatment withdrawal for placebo-randomised participants, whereas the other three studies reported higher treatment withdrawal rates for felbamate-randomised participants. Notably, the treatment withdrawal rates for felbamate treatment groups across all four studies remained reasonably low (less than 10%), suggesting that felbamate may be well tolerated. Felbamate-randomised participants most commonly withdrew from treatment due to adverse effects. The adverse effects consistently reported by all four studies were headache, dizziness and nausea. All three adverse effects were reported by 23% to 40% of felbamate-treated participants versus 3% to 15% of placebo-treated participants. We assessed the evidence for all outcomes using GRADE and rated the evidence as very low certainty, meaning that we have little confidence in the findings reported. We mainly downgraded evidence for imprecision due to the narrative synthesis conducted and the low number of events. We stress that the true effect of felbamate could likely be significantly different from that reported in this current review update.
AUTHORS' CONCLUSIONS
In view of the methodological deficiencies, the limited number of included studies and the differences in outcome measures, we have found no reliable evidence to support the use of felbamate as an add-on therapy in people with drug-resistant focal-onset epilepsy. A large-scale, randomised controlled trial conducted over a longer period of time is required to inform clinical practice.
Topics: Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Epilepsies, Partial; Felbamate; Humans; Quality of Life; Randomized Controlled Trials as Topic; Seizures; Single-Blind Method
PubMed: 35914010
DOI: 10.1002/14651858.CD008295.pub6