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Frontiers in Pharmacology 2020To evaluate efficacy, safety, and economics profiles of intravenous levetiracetam (LEV) for status epilepticus (SE).
OBJECTIVE
To evaluate efficacy, safety, and economics profiles of intravenous levetiracetam (LEV) for status epilepticus (SE).
METHODS
We searched PubMed, Embase, the Cochrane Library, Clinicaltrials.gov, and OpenGrey.eu for eligible studies published from inception to June 12 2019. Meta-analyses were conducted using random-effect model to calculate odds ratio (OR) of included randomized controlled trials (RCTs) with RevMan 5.3 software.
RESULTS
A total of 478 studies were obtained. Five systematic reviews (SRs)/meta-analyses, 9 RCTs, 1 non-randomized trial, and 27 case series/reports and 1 economic study met the inclusion criteria. Five SRs indicated no statistically significant difference in rates of seizure cessation when LEV was compared with lorazepam (LOR), phenytoin (PHT), or valproate (VPA). Pooled results of included RCTs indicated no statistically significant difference in seizure cessation when LEV was compared with LOR [OR = 1.04, 95% confidence interval (CI) 0.37 to 2.92], PHT (OR = 0.90, 95% CI 0.64 to 1.27), and VPA (OR = 1.47, 95% CI 0.81 to 2.67); and no statistically significant difference in seizure freedom within 24 h compared with LOR [OR = 1.83, 95% CI 0.57 to 5.90] and PHT (OR = 1.08, 95% CI 0.63 to 1.87). Meanwhile, LEV did not increase the risk of mortality during hospitalization compared with LOR (OR = 1.03, 95% CI 0.31 to 3.39), PHT (OR = 0.89, 95% CI 0.37 to 2.10), VPA (OR = 1.28, 95% CI 0.32 to 5.07), and placebo (plus clonazepam, OR = 0.73, 95% CI 0.16 to 3.38). LEV had lower need for artificial ventilation (OR = 0.23, 95% CI 0.06 to 0.92) and a lower risk of hypotension (OR = 0.15, 95% CI 0.03 to 0.84) compared to LOR. A trend of lower risk of hypotension and higher risk of agitation was found when LEV was compared with PHT. Case series and case report studies indicated psychiatric and behavioral adverse events of LEV. Cost-effectiveness evaluations indicated LEV as the most cost-effective non-benzodiazepines anti-epileptic drug (AED).
CONCLUSIONS
LEV has a similar efficacy as LOR, PHT, and VPA for SE, but a lower need for ventilator assistance and risk of hypotension, thus can be used as a second-line treatment for SE. However, more well-conducted studies to confirm the role of intravenous LEV for SE are still needed.
PubMed: 32670054
DOI: 10.3389/fphar.2020.00751 -
BMJ Clinical Evidence Oct 2007Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. Severe... (Review)
Review
INTRODUCTION
Head injury in young adults is often associated with motor vehicle accidents, violence, and sports injuries. In older adults it is often associated with falls. Severe head injury can lead to secondary brain damage from cerebral ischaemia resulting from hypotension, hypercapnia, and raised intracranial pressure. Severity of brain injury is assessed using the GCS. While about a quarter of people with severe brain injury (GCS score less than 8) will make a good recovery, about a third will die, and a fifth will have severe disability or be in a vegetative state.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of interventions to reduce complications of moderate to severe head injury as defined by Glasgow Coma Scale? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 17 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, anticonvulsants, corticosteroids, hyperventilation, hypothermia, and mannitol.
Topics: Acute Disease; Anticonvulsants; Brain Injuries; Craniocerebral Trauma; Glasgow Coma Scale; Humans; Hyperventilation; Injury Severity Score; Intracranial Hypertension; Mannitol; Phenytoin
PubMed: 19450357
DOI: No ID Found -
The Cochrane Database of Systematic... Jul 2008More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
More than three million persons are disabled by leprosy worldwide. The main complication of sensory nerve damage is neuropathic ulceration, particularly of the feet. In this review we explored interventions that can prevent and treat secondary damage to skin and limbs.
OBJECTIVES
To assess the effects of self-care, dressings and footwear in preventing and healing secondary damage to the skin in persons affected by leprosy.
SEARCH STRATEGY
We searched the Cochrane Skin Group Specialised Register (April 2008), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2008), MEDLINE (from 2003 to April 2008), EMBASE (from 2005 to April 2008), CINAHL (1982-2006) and LILACS (1982- April 2008 ) as well as online registers of ongoing trials (April 2008).
SELECTION CRITERIA
Randomised controlled trials involving anyone with leprosy and damage to peripheral nerves treated with any measures designed to prevent damage with the aim of healing existing ulcers and preventing development of new ulcers.
DATA COLLECTION AND ANALYSIS
Two authors assessed trial quality and extracted data.
MAIN RESULTS
Eight trials with a total of 557 participants were included. The quality of the trials was generally poor. The interventions and outcome measures were diverse. Although three studies that compared zinc tape to more traditional dressings found some benefit, none of these showed a statistically significant effect. One trial indicated that topical ketanserin had a better effect on wound healing than clioquinol cream or zinc paste, RR was 6.00 (95% CI 1.45 to 24.75). We did not combine the results of the two studies that compared topical phenytoin to saline dressing, but both studies found statistically significant effects in favour of phenytoin for healing of ulcer (SMD -2.34; 95% CI -3.30 to -1.39; and SMD -0.79; 95% CI -1.20 to 0.39). Canvas shoes were not much better than PVC-boots, and double rocker shoes did not promote healing much more than below-knee plasters.
AUTHORS' CONCLUSIONS
One study suggested that topical ketanserin is more effective than clioquinol cream or zinc paste. Topical phenytoin (two studies) may be more effective than saline dressing regarding ulcer healing. For the other dressings the results were equivocal. Canvas shoes were a little better than PVC-boots, but not significantly, and the effect of double rocker shoes compared to below-knee plasters was no different in promoting the healing of ulcers. No side effects were documented. There is a lack of high quality research in the field of ulcer prevention and treatment in leprosy. New trials should follow the current standards for design and reporting of randomised controlled trials.
Topics: Bandages; Humans; Leg Ulcer; Leprosy; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Skin Ulcer; Wound Healing
PubMed: 18646114
DOI: 10.1002/14651858.CD004833.pub3 -
CNS Neuroscience & Therapeutics Jun 2011Our aim was to evaluate the efficacy and tolerability of anticonvulsant agents for the treatment of acute bipolar mania and ascertain if their effects on mania are a... (Meta-Analysis)
Meta-Analysis Review
Our aim was to evaluate the efficacy and tolerability of anticonvulsant agents for the treatment of acute bipolar mania and ascertain if their effects on mania are a "class" effect. We conducted a systematic review of randomized controlled trials (RCTs) with placebo or active comparator, in acute bipolar mania in order to summarize available data on anticonvulsant treatment of mania/mixed episodes. We searched (PubMed/MEDLINE) with the combination of the words "acute mania" and "clinical trials" with each one of the following words: "anticonvulsants/antiepileptics,""valproic/valproate/divalproex,""carbamazepine,""oxcarbazepine,""lamotrigine,""gabapentin,""topiramate,""phenytoin,""zonisamide,""retigabine,""pregabalin,""tiagabine,""levetiracetam,""licarbazepine,""felbamate," and "vigabatrin." Original articles were found until November 1, 2008. Data from 35 randomized clinical trials suggested that not all anticonvulsants are efficacious for the treatment of acute mania. Valproate showed greater efficacy in reducing manic symptoms, with response rates around 50% compared to a placebo effect of 20-30%. It appears to have a more robust antimanic effect than lithium in rapid cycling and mixed episodes. As valproate, the antimanic effects of carbamazepine have been demonstrated. Evidences did not support the efficacy of the gabapentin, topiramate as well as lamotrigine as monotherapy in acute mania and mixed episodes. Oxcarbazepine data are inconclusive and data regarding other anticonvulsants are not available. Anticonvulsants are not a class when treating mania. While valproate and carbamazepine are significantly more effective than placebo, gabapentin, topiramate, and lamotrigine are not. However, some anticonvulsants may be efficacious in treating some psychiatric comorbidities that are commonly associated to bipolar illness.
Topics: Amines; Anticonvulsants; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Interactions; Drug Therapy, Combination; Fructose; Gabapentin; Humans; Lamotrigine; Lithium Compounds; Oxcarbazepine; Randomized Controlled Trials as Topic; Topiramate; Triazines; Valproic Acid; gamma-Aminobutyric Acid
PubMed: 20015083
DOI: 10.1111/j.1755-5949.2009.00089.x -
CNS Drugs Apr 2013Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug,... (Review)
Review
BACKGROUND
Partial-onset seizures contribute the bulk of seizure burden in childhood epilepsy. The therapeutic decision making involves consideration of factors specific to drug, patient and socioeconomic situation.
OBJECTIVES
This paper systematically reviews the available efficacy/effectiveness evidence for various anti-epileptic drugs (AED) as monotherapy and adjunctive therapy for partial-onset seizures in children.
DATA SOURCES
Relevant randomized clinical trials (RCTs) were identified by a structured PubMed search, supplemented by an additional hand search of reference lists and authors' files.
STUDY APPRAISAL AND SYNTHESIS METHODS
Eligible studies were reviewed and data extracted into tables. Included RCTs were classified based on accepted published criteria.
OUTCOMES
Only efficacy and effectiveness outcome measures were evaluated since there is little scientifically rigorous comprehensive AED adverse effects data.
RESULTS
Oxcarbazepine is the only AED with Class I evidence for efficacy/effectiveness as initial monotherapy for partial-onset seizures in children. Carbamazepine, clobazam, lamotrigine, phenobarbital, phenytoin, topiramate, valproate, vigabatrin and zonisamide have, at best, Class III efficacy/effectiveness evidence for monotherapy of partial-onset seizures in children. For adjunctive therapy, gabapentin, lamotrigine, levetiracetam, oxcarbazepine and topiramate have Class I efficacy/effectiveness evidence for treatment of pediatric partial-onset seizures.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
This efficacy/effectiveness analysis must not be used in isolation when selecting therapy. AED selection for a specific child needs to integrate a drug's efficacy/effectiveness data with its safety and tolerability profile, pharmacokinetic properties, available formulations, and patient specific characteristics. It is critical that physicians and patients incorporate all these relevant variables when choosing AED therapy.
Topics: Anticonvulsants; Child; Decision Making; Drug Approval; Epilepsies, Partial; Humans; Randomized Controlled Trials as Topic; Socioeconomic Factors; Treatment Outcome
PubMed: 23515971
DOI: 10.1007/s40263-013-0048-z -
BMJ (Clinical Research Ed.) Oct 1995To determine effectiveness and adverse effects of anticonvulsant drugs in management of pain. (Clinical Trial)
Clinical Trial Randomized Controlled Trial Review
OBJECTIVE
To determine effectiveness and adverse effects of anticonvulsant drugs in management of pain.
DESIGN
Systematic review of randomised controlled trials of anticonvulsants for acute, chronic, or cancer pain identified by using Medline, by hand searching, by searching reference lists, and by contacting investigators.
SUBJECTS
Between 1966 and February 1994, 37 reports were found; 20 reports, of four anticonvulsants, were eligible.
MAIN OUTCOME MEASURES
Numbers needed to treat were calculated for effectiveness, adverse effects, and drug related withdrawal from study.
RESULTS
The only placebo controlled study in acute pain found no analgesic effect of sodium valproate. For treating trigeminal neuralgia, carbamazepine had a combined number needed to treat of 2.6 for effectiveness, 3.4 for adverse effects, and 24 for severe effects (withdrawal from study). For treating diabetic neuropathy, anticonvulsants had a combined number needed to treat of 2.5 for effectiveness, 3.1 for adverse effects, and 20 for severe effects. For migraine prophylaxis, anticonvulsants had a combined number needed to treat of 1.6 for effectiveness, 2.4 for adverse effects, and 39 for severe effects. Phenytoin had no effect on the irritable bowel syndrome, and carbamazepine had little effect on pain after stroke. Clonazepam was effective in one study for temporomandibular joint dysfunction. No study compared one anticonvulsant with another.
CONCLUSIONS
Anticonvulsants were effective for trigeminal neuralgia and diabetic neuropathy and for migraine prophylaxis. Minor adverse effects occurred as often as benefit.
Topics: Anticonvulsants; Carbamazepine; Clonazepam; Diabetic Neuropathies; Humans; Pain; Phenytoin; Treatment Outcome; Trigeminal Neuralgia; Valproic Acid
PubMed: 7580659
DOI: 10.1136/bmj.311.7012.1047 -
PloS One 2022We systematically compared the effects of prophylactic anticonvulsant drug use in patients with traumatic brain injury. We searched four electronic databases from their... (Meta-Analysis)
Meta-Analysis
We systematically compared the effects of prophylactic anticonvulsant drug use in patients with traumatic brain injury. We searched four electronic databases from their inception until July 13, 2021. Two researchers independently screened, appraised, and extracted the included studies. Network meta-analysis using multivariate random effects and a frequentist framework was adopted for data analysis. The risk of bias of each study was assessed using the Cochrane risk of bias tool, and confidence in evidence was assessed through confidence in network meta-analysis (CINeMA). A total of 11 randomized controlled trials involving 2,450 participants and six different treatments (i.e., placebo, carbamazepine, phenytoin, levetiracetam, valproate, and magnesium sulfate) were included. We found that anticonvulsant drugs as a whole significantly reduced early posttraumatic seizures (PTS) but not late PTS compared with placebo (odd ratios [ORs] = 0.42 and 0.82, 95% confidence intervals [CIs] = 0.21-0.82 and 0.47-1.43). For the findings of network meta-analysis, we observed that phenytoin (ORs = 0.43 and 0.71; 95% CIs = 0.18-1.01 and 0.23-2.20), levetiracetam (ORs = 0.56 and 1.58; 95% CIs = 0.12-2.55 and 0.03-84.42), and carbamazepine (ORs = 0.29 and 0.64; 95% CIs = 0.07-1.18 and 0.08-5.28) were more likely to reduce early and late PTS compared with placebo; however, the treatment effects were not significant. Sensitivity analysis, after excluding a study enrolling only children, revealed that phenytoin had a significant effect in preventing early PTS (OR = 0.33; 95% CI = 0.14-0.78). Our findings indicate that no antiepileptic drug had an effect on early or late PTS superior to that of another; however, the sensitivity analysis revealed that phenytoin might prevent early PTS. Additional studies with large sample sizes and a rigorous design are required to obtain high-quality evidence on prophylactic anticonvulsant drug use in patients with traumatic brain injury.
Topics: Anticonvulsants; Brain Injuries, Traumatic; Carbamazepine; Child; Humans; Levetiracetam; Network Meta-Analysis; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Seizures
PubMed: 35358219
DOI: 10.1371/journal.pone.0265932 -
The Cochrane Database of Systematic... Aug 2015Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Head injury is a common event and can cause a spectrum of motor and cognition disabilities. A frequent complication is seizures. Antiepileptic drugs (AED) such as phenytoin are often used in clinical practice with the hopes of preventing post-traumatic epilepsy. Whether immediate medical intervention following head trauma with either AEDs or neuroprotective drugs can alter the process of epileptogenesis and lead to a more favorable outcome is currently unknown. This review attempted to address the effectiveness of these treatment interventions. This review updates and expands on the earlier Cochrane review.
OBJECTIVES
To compare the efficacy of antiepileptic drugs and neuroprotective agents with placebo, usual care or other pharmacologic agents for the prevention of post-traumatic epilepsy in people diagnosed with any severity of traumatic brain injury.
SEARCH METHODS
We searched The Cochrane Epilepsy Group's specialized register, CENTRAL, MEDLINE, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP) in January 2015. We searched EMBASE, Biological Abstracts and National Research Register in September 2014 and SCOPUS in December 2013. The Cochrane Epilepsy Group performed handsearches of relevant journals.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that include AEDs or neuroprotective agents compared with placebo, another pharmacologic agent or a usual care group. The outcomes measured included a seizure occurring within one week of trauma (early seizure), seizure occurring later than one week post-trauma (late seizure), mortality and any adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted the data. We calculated risk ratios (RR) and 95% confidence intervals (CI) for each outcome. We used random-effects models in the meta-analyses and performed pre-defined subgroup and sensitivity analyses.
MAIN RESULTS
This review included 10 RCTs (reported in 12 articles) consisting of 2326 participants The methodological quality of the studies varied. The type of intervention was separated into three categories; AED versus placebo or standard care, alternative neuroprotective agent versus placebo or standard care and AED versus other AED. Treatment with an AED (phenytoin or carbamazepine) decreased the risk of early seizure compared with placebo or standard care (RR 0.42, 95% CI 0.23 to 0.73; very low quality evidence). There was no evidence of a difference in the risk of late seizure occurrence between AEDs and placebo or standard care (RR 0.91, 95% CI 0.57 to 1.46; very low quality evidence). There was no evidence of a significant difference in all-cause mortality between AEDs and placebo or standard care (RR 1.08 95% CI 0.79 to 1.46,very low quality of evidence). Only one study looked at other potentially neuroprotective agents (magnesium sulfate) compared with placebo. The risk ratios were: late seizure 1.07 (95% CI 0.53 to 2.17) and all-cause mortality 1.20 (95% CI 0.80 to 1.81). The risk ratio for occurrence of early seizure was not estimable.Two studies looked at comparison of two AEDs (levetiracetam, valproate) with phenytoin used as the main comparator in each study. The risk ratio for all-cause mortality was 0.53 (95% CI 0.30 to 0.94). There was no evidence of treatment benefit of phenytoin compared with another AED for early seizures (RR 0.66, 95% 0.20 to 2.12) or late seizures(RR 0.77, 95% CI 0.46 to 1.30).Only two studies reported adverse events. The RR of any adverse event with AED compared with placebo was 1.65 (95% CI 0.73 to 3.66; low quality evidence). There were insufficient data on adverse events in the other treatment comparisons.
AUTHORS' CONCLUSIONS
This review found low-quality evidence that early treatment with an AED compared with placebo or standard care reduced the risk of early post-traumatic seizures. There was no evidence to support a reduction in the risk of late seizures or mortality. There was insufficient evidence to make any conclusions regarding the effectiveness or safety of other neuroprotective agents compared with placebo or for the comparison of phenytoin, a traditional AED, with another AED.
Topics: Adult; Anticonvulsants; Carbamazepine; Cause of Death; Child; Craniocerebral Trauma; Epilepsy; Humans; Levetiracetam; Magnesium Sulfate; Neuroprotective Agents; Phenytoin; Piracetam; Randomized Controlled Trials as Topic; Valproic Acid
PubMed: 26259048
DOI: 10.1002/14651858.CD009900.pub2 -
Seizure Apr 2021Spontaneous intracerebral haemorrhage (ICH) is associated with high mortality and high morbidity, including seizures. Seizure prophylaxis is "not recommended" by the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Spontaneous intracerebral haemorrhage (ICH) is associated with high mortality and high morbidity, including seizures. Seizure prophylaxis is "not recommended" by the American Stroke Association, but practice variation still exists due to inconclusive data. We performed a meta-analysis to assess the current relevant literature to determine the efficacy of seizure prophylaxis following ICH.
METHODS
We performed searches of PubMed, Scopus, and Embase up to September 15, 2020. We included observational and randomized controlled studies reporting seizure prophylaxis and occurrence in adults with ICH. Outcomes were seizures, as defined by the authors, within 14 days of ICH and at the longest point of follow-up. We used random-effects models to estimate the odds ratios (ORs) for seizure prophylaxis and outcomes. The PROSPERO registration was CRD42019140493.
RESULTS
We included 8 studies (2852 patients) in our analysis. The mean (± standard deviation) age of the pooled patients was 65 (±4) years; 39 % (± 5%) were female. Seizure prophylaxis did not prevent seizures at the longest follow-up time (OR 0.708, 95 % CI 0.438-1.143, p = 0.158, I2 = 34 %). This result was confirmed in subgroup analyses using categorical variables and in meta-regressions using continuous variables. Additionally, seizure prophylaxis was not associated with preventing early seizures, defined as < 14 days of ICH (OR 0.66, 95 % CI 0.21-2.08, p = 0.48, I2 = 35 %).
CONCLUSION
Seizure prophylaxis following ICH was not associated with seizure prevention in adults. Most included studies were observational. Further randomized controlled trials examining the efficacy of seizure prophylaxis in high-risk patients and different types of antiepileptic drugs are needed.
Topics: Aged; Anticonvulsants; Cerebral Hemorrhage; Female; Humans; Levetiracetam; Male; Middle Aged; Phenytoin; Piracetam; Seizures
PubMed: 33713891
DOI: 10.1016/j.seizure.2021.02.029 -
Seizure Feb 2015To review the evidence for efficacy and safety of lacosamide in adult patients with refractory epilepsy and refractory status epilepticus (RSE). (Review)
Review
PURPOSE
To review the evidence for efficacy and safety of lacosamide in adult patients with refractory epilepsy and refractory status epilepticus (RSE).
METHODS
A systematic literature search of MEDLINE, PubMed, EMBASE, IPA, Google and Google Scholar (through October 2014) was performed.
RESULTS
Fourteen studies assessing lacosamide in 3509 refractory epilepsy patients were included. In 3 RCTs, more patients had at least 50% reduction in seizure frequency with lacosamide compared to placebo with 38.3-41.1%, 38.1-41.2%, and 18.3-25.8%, in the 400 mg/day, 600 mg/day, and placebo groups, respectively. In non-comparative trials, 18-69% of patients achieved at least 50% reduction in seizure frequency, and 1.7-26.2% achieved seizure freedom. Non-responders were documented in two trials, with 26.2-34% having no response. Thirteen studies assessing lacosamide in 390 RSE patients were included. When assessing lacosamide's ability to terminate RSE, one comparative cohort study found no improvement in SE duration or seizure control with addition of lacosamide. Another study documented no difference compared to use of phenytoin. Eleven descriptive studies using lacosamide as add-on RSE therapy revealed seizure termination rates of 0-100% (median 64.7%). In all patients receiving lacosamide, dizziness (21.8%), vision disturbances (10.4%), drowsiness (7.4%), headache (7.0%), nausea (6.5%), and coordination problems (5.8%) were the most common adverse effects.
CONCLUSION
Based on evidence to date, adjunctive lacosamide is a treatment option to reduce seizure frequency in patients with refractory epilepsy and terminate seizures in patients with RSE. The safety information summary can be used to advise patients of potential adverse effects.
Topics: Acetamides; Anticonvulsants; Epilepsy; Humans; Lacosamide; Seizures
PubMed: 25645629
DOI: 10.1016/j.seizure.2014.11.007