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International Journal of Environmental... Jan 2022Dietary nitrate supplementation is evidenced to induce physiological effects on skeletal muscle function in fast-twitch muscle fibers and may enhance high-intensity... (Review)
Review
Dietary nitrate supplementation is evidenced to induce physiological effects on skeletal muscle function in fast-twitch muscle fibers and may enhance high-intensity exercise performance. An important component of sport-specific skills is the ability to perform explosive movements; however, it is unclear if nitrate supplementation can impact explosive efforts. We examined the existing evidence to determine whether nitrate supplementation improves explosive efforts lasting ≤ 6 s. PubMed, Scopus and Directory of Open Access Journals (DOAJ) were searched for articles using the following search strategy: (nitrate OR nitrite OR beetroot) AND (supplement OR supplementation) AND (explosive OR power OR high intensity OR high-intensity OR sprint* OR "athletic performance"). Out of 810 studies, 18 were eligible according to inclusion criteria. Results showed that 4 of the 10 sprint-type studies observed improved sprint time, power output, and total work in cycling or running, whereas 4 of the 10 resistance-based exercise studies observed improvements to power and velocity of free-weight bench press as well as isokinetic knee extension and flexion at certain angular velocities. These results suggest that nitrate potentially improves explosive exercise performance, but further work is required to clarify the factors influencing the efficacy of nitrate in different exercise modalities.
Topics: Athletic Performance; Dietary Supplements; Double-Blind Method; Explosive Agents; Nitrates; Nitrites
PubMed: 35055584
DOI: 10.3390/ijerph19020762 -
The Cochrane Database of Systematic... Jul 2020Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for treatment of type 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic efficacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD.
OBJECTIVES
To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease.
SEARCH METHODS
We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author.
MAIN RESULTS
Through our searches, we retrieved 99 unique records, of which two met our inclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the off-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0.09). The difference in scores was slightly greater when scores were adjusted for baseline severity of the condition (as reported by study authors) (MD -3.5, 95% CI -6.7 to -0.3), exceeding the minimum clinically important difference (MCID). We found low-certainty evidence suggesting that exenatide has little or no effect on health-related quality of life (HRQoL) as assessed by the Parkinson's Disease Questionnaire (PDQ)-39 Summary Index (SI) (MD -1.80, 95% CI -6.95 to 3.35), the EuroQol scale measuring health status in five dimensions (EQ5D) (MD 0.07, 95% CI -0.03 to 0.16), or the EQ5D visual analogue scale (VAS) (MD 5.00, 95% CI -3.42 to 13.42). Eight serious adverse events (SAEs) were recorded, but all were considered unrelated to the intervention. Low-certainty evidence suggests that exenatide has little or no effect on weight loss (risk ratio (RR) 1.25, 95% CI 0.89 to 1.76). Exenatide versus no treatment Primary outcomes at 14 months We found very low-certainty evidence suggesting that exenatide improves motor impairment as assessed by MDS-UPDRS Part III off medication (MD -4.50, 95% CI -8.64 to -0.36), exceeding the MCID. We are uncertain whether exenatide improves HRQoL as assessed by the PDQ-39 SI (MD 3.50, 95% CI -2.75 to 9.75; very low-quality evidence). We found very low-certainty evidence suggesting that exenatide has little or no effect on the number of SAEs (RR 1.60, 95% 0.40 to 6.32). We found very low-certainty evidence suggesting that exenatide may lead to weight loss (MD -2.40 kg, 95% CI -4.56 to -0.24). Primary outcomes at 24 months We found evidence as reported by study authors to suggest that exenatide improves motor impairment as measured by MDS-UPDRS Part III off medication (MD 5.6 points, 95% CI 2.2 to 9.0). Exenatide may not improve HRQoL as assessed by the PDQ-39 SI (P = 0.682) and may not result in weight loss (MD 0.1 kg, 95% CI 3.0 to 2.8).
AUTHORS' CONCLUSIONS
Low- or very low-certainty evidence suggests that exenatide may improve motor impairment for people with PD. The difference in motor impairment observed between groups may persist for some time following cessation of exenatide. This raises the possibility that exenatide may have a disease-modifying effect. SAEs were unlikely to be related to treatment. The effectiveness of exenatide for improving HRQoL, non-motor outcomes, ADLs, and psychological outcomes is unclear. Ongoing studies are assessing other GLP-1 receptor agonists.
Topics: Bias; Double-Blind Method; Exenatide; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Parkinson Disease; Placebos; Quality of Life; Randomized Controlled Trials as Topic; Self Administration; Single-Blind Method
PubMed: 32700772
DOI: 10.1002/14651858.CD012990.pub2 -
CNS Drugs Mar 2021Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A...
BACKGROUND
Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex.
OBJECTIVES
This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox-Gastaut syndrome.
METHODS
The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes.
RESULTS
Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.
CONCLUSIONS
The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.
Topics: Anticonvulsants; Cannabidiol; Case-Control Studies; Cross-Sectional Studies; Double-Blind Method; Epilepsies, Myoclonic; Epilepsy; Epileptic Syndromes; Humans; Lennox Gastaut Syndrome; Seizures
PubMed: 33754312
DOI: 10.1007/s40263-021-00807-y -
Nutricion Hospitalaria Dec 2021Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy...
Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and 'at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.
Topics: Adult; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Randomized Controlled Trials as Topic; Vitamin B Complex
PubMed: 34530623
DOI: 10.20960/nh.03631 -
Nutrients Nov 2021There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of... (Meta-Analysis)
Meta-Analysis
Oral Magnesium Supplementation for Treating Glucose Metabolism Parameters in People with or at Risk of Diabetes: A Systematic Review and Meta-Analysis of Double-Blind Randomized Controlled Trials.
There is a large and growing body of literature focusing on the use of oral magnesium (Mg) supplementation for improving glucose metabolism in people with or at risk of diabetes. We therefore aimed to investigate the effect of oral Mg supplementation on glucose and insulin-sensitivity parameters in participants with diabetes or at high risk of diabetes, compared with a placebo. Several databases were searched investigating the effect of oral Mg supplementation vs placebo in patients with diabetes or conditions at high risk of diabetes. Data were reported as standardized mean differences (SMDs) with their 95% confidence intervals (CIs) using follow-up data of glucose and insulin-sensitivity parameters. Compared with placebo, Mg supplementation reduced fasting plasma glucose in people with diabetes. In people at high risk of diabetes, Mg supplementation significantly improved plasma glucose per se, and after a 2 h oral glucose tolerance test. Furthermore, Mg supplementation demonstrated an improvement in insulin sensitivity markers. In conclusion, Mg supplementation appears to have a beneficial role and improves glucose parameters in people with diabetes. Moreover, our work indicates that Mg supplementation may improve insulin-sensitivity parameters in those at high risk of diabetes.
Topics: Blood Glucose; Diabetes Mellitus; Dietary Supplements; Double-Blind Method; Glucose Tolerance Test; Humans; Insulin Resistance; Magnesium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34836329
DOI: 10.3390/nu13114074 -
Cephalalgia : An International Journal... Mar 2023We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. (Meta-Analysis)
Meta-Analysis
Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature.
BACKGROUND
We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks.
METHODS
MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines.
RESULTS
Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan.
CONCLUSION
Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself. CRD42022308224.
Topics: Adult; Humans; Network Meta-Analysis; Double-Blind Method; Migraine Disorders; Treatment Outcome
PubMed: 36786357
DOI: 10.1177/03331024231151419 -
Drugs Feb 2022Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) are antiseizure medications (ASMs) approved for adjunctive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) are antiseizure medications (ASMs) approved for adjunctive treatment of focal-onset seizures. So far, no randomised controlled trial directly compared the efficacy and safety of these drugs.
OBJECTIVE
We estimated the comparative efficacy and safety of these ASMs for the treatment of focal-onset seizures in adults with epilepsy using a network meta-analysis (NMA).
METHODS
We systematically searched (June week 4, 2021) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ). There were no date limitations or language restrictions. Randomised, double-blinded, controlled, parallel-group, add-on studies that compared oral BRV, CNB, ESL, LCM, and PER versus any comparator over maintenance periods of at least 12 weeks and included adult patients with focal seizures uncontrolled by concomitant ASMs were identified. The efficacy outcomes were the proportions of patients with ≥ 50% and 100% reduction in baseline seizure frequency during the maintenance period. The tolerability outcomes were the proportions of participants who experienced at least one treatment-emergent adverse event (TEAE) and experienced at least one TEAE leading to discontinuation. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA).
RESULTS
Sixteen trials (BRV: n = 3, CNB: n = 1, ESL: n = 4, LCM: n = 4, PER: n = 4) were included, overall enrolling 4507 patients randomised to add-on active treatments (BRV = 803, CNB = 221, ESL =9 90, LCM = 1104, and PER = 1389) and 2246 to add-on placebo. Cenobamate was associated with a higher rate of ≥ 50% seizure frequency reduction than BRV [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.11-3.66], ESL (OR 1.93, 95% CI 1.07-3.48), LCM (OR 1.86, 95% CI 1.04-3.32), and PER (OR 2.07, 95% CI 1.16-3.70). There was a not statistically significant trend favouring CNB over ESL, LCM and PER for the seizure freedom outcome. Brivaracetam (OR 0.61, 95% CI 0.44-0.86) and LCM (OR 0.60, 95% CI 0.40-0.88) were associated with a lower proportion of participants experiencing TEAEs compared to ESL, and patients treated with PER were associated with a higher risk to experience at least one TEAE (OR 1.42, 95% CI 1.02-1.96) than BRV. According to SUCRA, CNB had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction, and BRV and LCM had the highest probabilities of being the best-tolerated treatments.
CONCLUSIONS
Cenobamate ranked best for efficacy, and BRV and LCM were best tolerated over the other comparators. Although NMAs cannot replace direct comparisons, they may support physicians in clinical decision making.
Topics: Adult; Anticonvulsants; Carbamates; Chlorophenols; Dibenzazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lacosamide; Male; Middle Aged; Network Meta-Analysis; Nitriles; Pyridones; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures; Tetrazoles
PubMed: 35061214
DOI: 10.1007/s40265-021-01661-4 -
PloS One 2023Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so...
INTRODUCTION
Second-generation antipsychotics (SGAs) are frequently prescribed for the treatment of resistant anorexia nervosa. However, few clinical trials have been conducted so far and no pharmacological treatment has yet been approved by the Food and Drug Administration. The aim of this paper is to conduct a systematic scoping review exploring the effectiveness and safety of atypical antipsychotics in anorexia nervosa (AN).
METHOD
We conducted a systematic scoping review of the effectiveness and tolerability of SGAs in the management of AN. We included articles published from January 1, 2000, through September 12, 2022 from the PubMed and PsycInfo databases and a complementary manual search. We selected articles about adolescents and adults treated for AN by four SGAs (risperidone, quetiapine, aripiprazole or olanzapine). This work complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRIMA-ScR) and was registered in the Open Science Framework (OSF) repository.
RESULTS
This review included 55 articles: 48 assessing the effectiveness of SGAs in AN and 7 focusing only on their tolerability and safety. Olanzapine is the treatment most frequently prescribed and studied with 7 randomized double-blind controlled trials. Other atypical antipsychotics have been evaluated much less often, such as aripiprazole (no randomized trials), quetiapine (two randomized controlled trials), and risperidone (one randomized controlled trial). These treatments are well tolerated with mild and transient adverse effects in this population at particular somatic risk.
DISCUSSION
Limitations prevent the studies both from reaching conclusive, reliable, robust, and reproducible results and from concluding whether or not SGAs are effective in anorexia nervosa. Nonetheless, they continue to be regularly prescribed in clinical practice. International guidelines suggest that olanzapine and aripiprazole can be interesting in severe or first-line resistant clinical situations.
Topics: Adult; Adolescent; Humans; Antipsychotic Agents; Olanzapine; Risperidone; Aripiprazole; Quetiapine Fumarate; Anorexia Nervosa; Benzodiazepines; Randomized Controlled Trials as Topic
PubMed: 36928656
DOI: 10.1371/journal.pone.0278189 -
Schizophrenia Bulletin Jul 2023Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND HYPOTHESIS
Psychotic experiences (PEs) are associated with increased risk for mental disorders, in particular persistent PEs. PEs therefore might be useful within intervention research. We sought to systematically determine the incidence and persistence of PEs in the general population.
STUDY DESIGN
A double-blind search of databases (Embase, Pubmed PMC, Psychinfo, Medline, and Web of Science) from inception to January 2023 and data extraction, were conducted. Study quality was assessed using the NIH assessment tool. Random effects models were conducted to calculate pooled incidence rate per person-year and proportion of persistent PEs per year. Age and study design were all examined using subgroup analyses. Demographic, risk factors, and outcomes for incidence and persistence of PEs were reported in a narrative synthesis.
STUDY RESULTS
Using a double-blind screening method for abstract (k = 5763) and full text (k = 250) were screened. In total 91 samples from 71 studies were included, of which 39 were included in a meta-analysis (incidence: k = 17, n = 56 089; persistence: k = 22, n = 81 847). Incidence rate was 0.023 per person-year (95% CI [0.0129;0.0322]). That is, for every 100 people, 2 reported first onset PEs in a year. This was highest in adolescence at 5 per 100(13-17 years). The pooled persistence rate for PEs was 31.0% (95% CI [26.65,35.35]) This was highest in adolescence at 35.8%. Cannabis was particularly associated with incidence of PEs, and persistence of PEs were associated with multiple mental disorders.
CONCLUSIONS
Each year incidence of PEs is 2 of every 100 people, and persists each year in 31% of cases, this risk is highest in adolescents.
Topics: Adolescent; Humans; Psychotic Disorders; Incidence; Mental Disorders; Risk Factors; Randomized Controlled Trials as Topic
PubMed: 37402250
DOI: 10.1093/schbul/sbad056 -
The Cochrane Database of Systematic... Mar 2022This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30%... (Review)
Review
BACKGROUND
This is an updated version of the Cochrane Review previously published in 2019. Epilepsy is one of the most common neurological disorders. It is estimated that up to 30% of individuals with epilepsy continue to have epileptic seizures despite treatment with an antiepileptic drug. These patients are classified as drug-resistant and require treatment with a combination of multiple antiepileptic drugs. Brivaracetam is a third-generation antiepileptic drug that is a high-affinity ligand for synaptic vesicle protein 2A. In this review we investigated the use of brivaracetam as add-on therapy for epilepsy.
OBJECTIVES
To evaluate the efficacy and tolerability of brivaracetam when used as add-on treatment for people with drug-resistant epilepsy.
SEARCH METHODS
For the latest update we searched the following databases on 7 September 2021: the Cochrane Register of Studies (CRS Web); MEDLINE (Ovid) 1946 to 3 September 2021. CRS Web includes randomised controlled trials (RCTs) and quasi-RCTs from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy.
SELECTION CRITERIA
We searched for parallel-group RCTs that recruited people of any age with drug-resistant epilepsy. We accepted studies with any level of blinding (double-blind, single-blind, or unblinded).
DATA COLLECTION AND ANALYSIS
In accordance with standard Cochrane methodological procedures, two review authors independently assessed trials for inclusion before evaluating trial quality and extracting relevant data. The primary outcome to be assessed was 50% or greater reduction in seizure frequency. Secondary outcomes were: seizure freedom, treatment withdrawal for any reason, treatment withdrawal due to adverse events, the proportion of participants who experienced any adverse events, and drug interactions. We used an intention-to-treat population for all primary analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs).
MAIN RESULTS
We did not identify any new studies for this update, therefore the results and conclusions of the review are unchanged. The previous review included six studies involving a total of 2411 participants. Only one study included participants with both focal and generalised onset seizures; the other five trials included participants with focal onset seizures only. Study participants were aged 16 to 80 years. Treatment periods ranged from 7 to 16 weeks. We judged two studies to have low risk of bias and four to have unclear risk of bias. Details on the method used for allocation concealment and how blinding was maintained were insufficient in one study each. One study did not report all outcomes prespecified in the trial protocol, and there were discrepancies in reporting in a further study. Participants receiving brivaracetam add-on were more likely to experience a 50% or greater reduction in seizure frequency than those receiving placebo (RR 1.81, 95% CI 1.53 to 2.14; 6 studies; moderate-certainty evidence). Participants receiving brivaracetam were more likely to attain seizure freedom; however, the evidence is of low certainty (RR 5.89, 95% CI 2.30 to 15.13; 6 studies). The incidence of treatment withdrawal for any reason was slightly greater for participants receiving brivaracetam compared to those receiving placebo (RR 1.27, 95% CI 0.94 to 1.74; 6 studies; low-certainty evidence). The risk of participants experiencing one or more adverse events did not differ significantly following treatment with brivaracetam compared to placebo (RR 1.08, 95% CI 1.00 to 1.17; 5 studies; moderate-certainty evidence). However, participants receiving brivaracetam did appear to be more likely to withdraw from treatment due to adverse events compared with those receiving placebo (RR 1.54, 95% CI 1.02 to 2.33; 6 studies; low-certainty evidence).
AUTHORS' CONCLUSIONS
When used as add-on therapy for individuals with drug-resistant epilepsy, brivaracetam may be effective in reducing seizure frequency and may aid patients in achieving seizure freedom. However, add-on brivaracetam is probably associated with a greater proportion of treatment withdrawals due to adverse events compared with placebo. It is important to note that only one of the eligible studies included participants with generalised epilepsy. None of the included studies involved participants under the age of 16, and all studies were of short duration. Consequently, the findings of this review are mainly applicable to adult patients with drug-resistant focal epilepsy. Future research should focus on investigating the tolerability and efficacy of brivaracetam during longer-term follow-up, as well as assess the efficacy and tolerability of add-on brivaracetam in managing other types of seizures and in other age groups.
Topics: Adult; Anticonvulsants; Drug Resistant Epilepsy; Drug Therapy, Combination; Epilepsy, Generalized; Humans; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures
PubMed: 35285519
DOI: 10.1002/14651858.CD011501.pub3