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Psychiatric Services (Washington, D.C.) Apr 2021Two primary compounds of the cannabis plant (), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), differentially and dose-dependently affect mood and anxiety. In...
OBJECTIVE
Two primary compounds of the cannabis plant (), delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), differentially and dose-dependently affect mood and anxiety. In this systematic review, the authors summarize the design and results of controlled trials assessing the effects of THC and CBD on affective disorders, anxiety disorders, and posttraumatic stress disorder (PTSD).
METHODS
A keyword search of eight online literature databases identified eight randomized controlled trials of defined CBD or THC doses for the target populations.
RESULTS
A 1-month trial of daily THC (up to 3 mg per day) for anxiety disorder reduced anxiety symptoms, but symptoms were very low throughout the study. Another trial of sequential, single-day, low-dose THC in social anxiety disorder found no symptom changes. Two studies reported that single-dose CBD pretreatment reduced anxiety in laboratory paradigms among individuals with social anxiety disorder. A study of daily CBD for 4 weeks among adolescents with social anxiety disorder indicated modest symptom improvements. One crossover trial involving 10 patients with PTSD showed that THC added to standard pharmacotherapy reduced self-reported nightmares. Two small studies of THC for hospitalized patients with unipolar or bipolar depression found no improvement of depression; instead, anxiety and psychotic symptoms emerged in >50% of patients.
CONCLUSIONS
With only eight very small studies, insufficient evidence was found for efficacy of CBD and THC to manage affective disorders, anxiety disorders, or PTSD. Therefore, medical cannabis should not be recommended for treating patients with these disorders. Further research should investigate the safety and efficacy of managing psychiatric disorders with cannabinoids.
Topics: Adolescent; Anxiety Disorders; Cannabidiol; Cannabinoids; Humans; Mood Disorders; Stress Disorders, Post-Traumatic
PubMed: 33530732
DOI: 10.1176/appi.ps.202000189 -
Health Technology Assessment... Mar 2022Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded...
BACKGROUND
Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting.
OBJECTIVES
To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.
DATA SOURCES
We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020.
REVIEW METHODS
Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively.
RESULTS
Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness.
LIMITATIONS
The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.
CONCLUSIONS
Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020201953.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in ; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.
Topics: Adult; Anticonvulsants; Emergency Service, Hospital; Hospitals; Humans; Retrospective Studies; Status Epilepticus
PubMed: 35333156
DOI: 10.3310/RSVK2062 -
The International Journal of... Apr 2020Resistant bipolar disorder is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic...
BACKGROUND
Resistant bipolar disorder is a major mental health problem related to significant disability and overall cost. The aim of the current study was to perform a systematic review of the literature concerning (1) the definition of treatment resistance in bipolar disorder, (2) its clinical and (3) neurobiological correlates, and (4) the evidence-based treatment options for treatment-resistant bipolar disorder and for eventually developing guidelines for the treatment of this condition.
MATERIALS AND METHODS
The PRISMA method was used to identify all published papers relevant to the definition of treatment resistance in bipolar disorder and the associated evidence-based treatment options. The MEDLINE was searched to April 22, 2018.
RESULTS
Criteria were developed for the identification of resistance in bipolar disorder concerning all phases. The search of the literature identified all published studies concerning treatment options. The data were classified according to strength, and separate guidelines regarding resistant acute mania, acute bipolar depression, and the maintenance phase were developed.
DISCUSSION
The definition of resistance in bipolar disorder is by itself difficult due to the complexity of the clinical picture, course, and treatment options. The current guidelines are the first, to our knowledge, developed specifically for the treatment of resistant bipolar disorder patients, and they also include an operationalized definition of treatment resistance. They were based on a thorough and deep search of the literature and utilize as much as possible an evidence-based approach.
Topics: Anticonvulsants; Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Drug Resistance; Evidence-Based Medicine; Humans; Practice Guidelines as Topic
PubMed: 31802122
DOI: 10.1093/ijnp/pyz064 -
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 -
Epileptic Disorders : International... Dec 2022We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants,...
We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.
Topics: Breast Feeding; Cannabidiol; Carbamazepine; Child; Clobazam; Clonazepam; Epilepsy; Ethosuximide; Everolimus; Felbamate; Female; Fenfluramine; Gabapentin; Humans; Infant; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenobarbital; Phenytoin; Prospective Studies; Tiagabine; Topiramate; Valproic Acid; Vigabatrin; Zonisamide
PubMed: 36193017
DOI: 10.1684/epd.2022.1492 -
The Cochrane Database of Systematic... Aug 2020Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is...
BACKGROUND
Asthma is an illness that commonly affects adults and children, and it serves as a common reason for children to attend emergency departments. An asthma exacerbation is characterised by acute or subacute worsening of shortness of breath, cough, wheezing, and chest tightness and may be triggered by viral respiratory infection, poor compliance with usual medication, a change in the weather, or exposure to allergens or irritants. Most children with asthma have mild or moderate exacerbations and respond well to first-line therapy (inhaled short-acting beta-agonists and systemic corticosteroids). However, the best treatment for the small proportion of seriously ill children who do not respond to first-line therapy is not well understood. Currently, a large number of treatment options are available and there is wide variation in management.
OBJECTIVES
Main objective - To summarise Cochrane Reviews with or without meta-analyses of randomised controlled trials on the efficacy and safety of second-line treatment for children with acute exacerbations of asthma (i.e. after first-line treatments, titrated oxygen delivery, and administration of intermittent inhaled short-acting beta-agonists and oral corticosteroids have been tried and have failed) Secondary objectives - To identify gaps in the current evidence base that will inform recommendations for future research and subsequent Cochrane Reviews - To categorise information on reported outcome measures used in trials of escalation of treatment for acute exacerbations of asthma in children, and to make recommendations for development and reporting of standard outcomes in future trials and reviews - To identify relevant randomised controlled trials that have been published since the date of publication of each included review METHODS: We included Cochrane Reviews assessing interventions for children with acute exacerbations of asthma. We searched the Cochrane Database of Systematic Reviews. The search is current to 28 December 2019. We also identified trials that were potentially eligible for, but were not currently included in, published reviews. We assessed the quality of included reviews using the ROBIS criteria (tool used to assess risk of bias in systematic reviews). We presented an evidence synthesis of data from reviews alongside an evidence map of clinical trials. Primary outcomes were length of stay, hospital admission, intensive care unit admission, and adverse effects. We summarised all findings in the text and reported data for each outcome in 'Additional tables'.
MAIN RESULTS
We identified 17 potentially eligible Cochrane Reviews but extracted data from, and rated the quality of, 13 reviews that reported results for children alone. We excluded four reviews as one did not include any randomised controlled trials (RCTs), one did not provide subgroup data for children, and the last two had been updated and replaced by subsequent reviews. The 13 reviews included 67 trials; the number of trials in each review ranged from a single trial up to 27 trials. The vast majority of comparisons included between one and three trials, involving fewer than 100 participants. The total number of participants included in reviews ranged from 40 to 2630. All studies included children; 16 (24%) included children younger than two years of age. Most of the reviews reported search dates older than four years. We have summarised the published evidence as outlined in Cochrane Reviews. Key findings, in terms of our primary outcomes, are that (1) intravenous magnesium sulfate was the only intervention shown to reduce hospital length of stay (high-certainty evidence); (2) no evidence suggested that any intervention reduced the risk of intensive care admission (low- to very low-certainty evidence); (3) the risk of hospital admission was reduced by the addition of inhaled anticholinergic agents to inhaled beta-agonists (moderate-certainty evidence), the use of intravenous magnesium sulfate (high-certainty evidence), and the use of inhaled heliox (low-certainty evidence); (4) the addition of inhaled magnesium sulfate to usual bronchodilator therapy appears to reduce serious adverse events during hospital admission (moderate-certainty evidence); (5) aminophylline increased vomiting compared to placebo (moderate-certainty evidence) and increased nausea and nausea/vomiting compared to intravenous beta-agonists (low-certainty evidence); and (6) the addition of anticholinergic therapy to short-acting beta-agonists appeared to reduce the risk of nausea (high-certainty evidence) and tremor (moderate-certainty evidence) but not vomiting (low-certainty evidence). We considered 4 of the 13 reviews to be at high risk of bias based on the ROBIS framework. In all cases, this was due to concerns regarding identification and selection of studies. The certainty of evidence varied widely (by review and also by outcome) and ranged from very low to high.
AUTHORS' CONCLUSIONS
This overview provides the most up-to-date evidence on interventions for escalation of therapy for acute exacerbations of asthma in children from Cochrane Reviews of randomised controlled trials. A vast majority of comparisons involved between one and three trials and fewer than 100 participants, making it difficult to assess the balance between benefits and potential harms. Due to the lack of comparative studies between various treatment options, we are unable to make firm practice recommendations. Intravenous magnesium sulfate appears to reduce both hospital length of stay and the risk of hospital admission. Hospital admission is also reduced with the addition of inhaled anticholinergic agents to inhaled beta-agonists. However, further research is required to determine which patients are most likely to benefit from these therapies. Due to the relatively rare incidence of acute severe paediatric asthma, multi-centre research will be required to generate high-quality evidence. A number of existing Cochrane Reviews should be updated, and we recommend that a new review be conducted on the use of high-flow nasal oxygen therapy. Important priorities include development of an internationally agreed core outcome set for future trials in acute severe asthma exacerbations and determination of clinically important differences in these outcomes, which can then inform adequately powered future trials.
Topics: Acute Disease; Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Aminophylline; Anti-Asthmatic Agents; Anti-Bacterial Agents; Asthma; Bias; Bronchodilator Agents; Child; Child, Preschool; Cholinergic Antagonists; Disease Progression; Helium; Humans; Infant; Length of Stay; Leukotriene Antagonists; Magnesium Sulfate; Nausea; Oxygen; Positive-Pressure Respiration; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Vomiting; Work of Breathing
PubMed: 32767571
DOI: 10.1002/14651858.CD012977.pub2 -
Canadian Journal of Psychiatry. Revue... Apr 2020
Topics: Bipolar Disorder; Cannabidiol; Cannabinoid Receptor Modulators; Humans; Mood Disorders
PubMed: 31830820
DOI: 10.1177/0706743719895195 -
European Review For Medical and... Jul 2023The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of the study was to summarize the findings of the studies documenting the efficacy and safety of perampanel when used in children/adolescents or adults, either as add-on therapy or as monotherapy.
MATERIALS AND METHODS
A systematic search was conducted using PubMed, EMBASE and Scopus. Only studies with a cohort-based approach (either prospective or retrospective) were included. We were interested in real-world studies and therefore, studies with a highly regulated environment, such as randomized controlled trials, were excluded. The primary outcomes of interest were retention rates, response rates and seizure-free rates. Random effects model was used for the analysis. Effect sizes were reported as pooled prevalence along with 95% confidence intervals.
RESULTS
A total of 34 studies were included. The retention rates, within 24 months from initiation of treatment as an add-on therapy, ranged between 65% to 77% among children and adolescents. For adults, the retention rate varied between 56 to 77% within 24 months from initiation of treatment. The response rate was around 70% in children/adolescents and 52% in adults at 24 months of follow-up. Around 25% of children and adolescents and 37% of adults were seizure-free at 24 months follow-up period. The proportion of children/adolescents and adults reporting any treatment-related adverse effects was 29% and 41%, respectively. The commonly reported adverse effects were dizziness/drowsiness, somnolence, behavioral problems (irritability, aggression, anxiety, mood changes), postural instability/gait problems, fatigue and weight gain.
CONCLUSIONS
Perampanel might be an effective anti-epileptic drug in both children/adolescents and adults when used as an adjunct therapy. More data is required to comment on its use as monotherapy. Careful monitoring for psychiatric problems and behavioral disturbances is required, both prior to initiating treatment as well as during the course of management. Studies with long-term follow-up may are needed to confirm the findings of this meta-analysis.
Topics: Adult; Child; Adolescent; Humans; Anticonvulsants; Epilepsies, Partial; Retrospective Studies; Prospective Studies; Epilepsy; Nitriles; Treatment Outcome
PubMed: 37458642
DOI: 10.26355/eurrev_202307_32957 -
Clinical Pharmacology and Therapeutics Dec 2022The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics...
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.
Topics: Humans; Pharmacogenomic Testing; Pharmacogenetics; Cost-Benefit Analysis; Warfarin; Carbamazepine
PubMed: 36149409
DOI: 10.1002/cpt.2754 -
The Cochrane Database of Systematic... Nov 2021Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME).... (Review)
Review
BACKGROUND
Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2019.
OBJECTIVES
To evaluate the efficacy and tolerability of topiramate in the treatment of JME.
SEARCH METHODS
For the latest update, we searched the Cochrane Register of Studies (CRS Web) on 26 August 2021, and MEDLINE (Ovid 1946 to 26 August 2021). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality of the studies.
MAIN RESULTS
We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or greater reduction in primarily generalized tonic-clonic seizures (PGTCS), compared with participants in the placebo group (RR 4.00, 95% CI 1.08 to 14.75; 1 study, 22 participants; very low-certainty evidence). There were no significant differences between topiramate and valproate for participants responding with a 50% or greater reduction in myoclonic seizures (RR 0.88, 95% CI 0.67 to 1.15; one study, 23 participants; very-low certainty evidence) or in PGTCS (RR 1.22, 95% CI 0.68 to 2.21; one study, 16 participants, very-low certainty evidence), or participants becoming seizure-free (RR 1.13, 95% CI 0.61 to 2.11; one study, 27 participants; very-low certainty evidence). Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints (2 studies, 61 participants; very low-certainty evidence). Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged the studies to be at low to unclear risk of bias for the remaining domains (selection bias, performance bias, detection bias and other bias). We judged the overall certainty of the evidence for the outcomes as very low using the GRADE approach.
AUTHORS' CONCLUSIONS
We have found no new studies since the last version of this review was published in 2019. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.
Topics: Anticonvulsants; Humans; Myoclonic Epilepsy, Juvenile; Randomized Controlled Trials as Topic; Seizures; Topiramate; Valproic Acid
PubMed: 34817852
DOI: 10.1002/14651858.CD010008.pub5