Anthony G Marson

University of Liverpool, Liverpool, England, United Kingdom

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Publications (100)687.55 Total impact

  • Cochrane database of systematic reviews (Online) 06/2015; · 5.70 Impact Factor
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    ABSTRACT: Objective Carbamazepine causes severe cutaneous adverse drug reactions that may be predicted by the presence of the HLA-A*31:01 allele in northern European populations. There is uncertainty as to whether routine testing of patients with epilepsy is cost-effective. We conducted an economic evaluation of HLA-A*31:01 testing from the perspective of the National Health Service (NHS) in the United Kingdom.MethodsA short-term, decision analytic model was developed to estimate the outcomes and costs associated with a policy of routine testing (with lamotrigine prescribed for patients who test positive) versus the current standard of care, which is carbamazepine prescribed without testing. A Markov model was used to estimate total costs and quality-adjusted life-years (QALYs) over a lifetime to account for differences in drug effectiveness and the long-term consequences of adverse drug reactions.ResultsTesting reduced the expected rate of cutaneous adverse drug reactions from 780 to 700 per 10,000 patients. The incremental cost-effectiveness ratio for pharmacogenetic testing versus standard care was £12,808 per QALY gained. The probability of testing being cost-effective at a threshold of £20,000 per QALY was 0.80, but the results were sensitive to estimated remission rates for alternative antiepileptic drugs (AEDs).SignificanceRoutine testing for HLA-A*31:01 in order to reduce the incidence of cutaneous adverse drug reactions in patients being prescribed carbamazepine for epilepsy is likely to represent a cost-effective use of health care resources.
    Epilepsia 02/2015; DOI:10.1111/epi.12937 · 4.58 Impact Factor
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    ABSTRACT: To compare quality-of-life (QoL) outcomes over 2 years following initiation of treatment with a standard or newer antiepileptic drug (AED) in adults with new-onset epilepsy. To examine the impact of seizure remission and failure of initial treatment on QoL outcomes measured over 2 years. We conducted a pragmatic, randomized, unblinded, multicenter, parallel-group clinical trial (the Standard and New Antiepileptic Drugs [SANAD] trial) comparing clinical and cost effectiveness of initiating treatment with carbamazepine versus lamotrigine, gabapentin, oxcarbazepine and topiramate, and valproate versus lamotrigine and topiramate. QoL data were collected by mail at baseline, 3 months, and at 1 and 2 years using validated measures. These data were analyzed using longitudinal data models. Continuous QoL measures, time to 12-month remission and time to treatment withdrawal were explored using joint models. Baseline questionnaires were returned by 1,575 adults; 1,439 returned the 3-month questionnaire, 1,274 returned the 1-year questionnaire, and 1,121 returned the 2-year questionnaire. There were few statistically significant differences between drugs over 2 years in QoL outcomes. Significant association was identified between QoL scores over the 2-year time frame and the risk of experiencing a 12-month remission or treatment withdrawal over that period. The choice of initial treatment had no significant effect on QoL by 2-year follow-up. However, overall QoL was reduced with continued seizures, adverse events, and failure of the initial treatment. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.
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    ABSTRACT: The objectives are as follows: To review the time to withdrawal, remission and first seizure of 10 antiepileptic drugs (carbamazepine, phenytoin, valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, levetiracetam, zonisamide) currently used as monotherapy in children and adults with partial onset seizures or generalised tonic-clonic seizures with or without other generalised seizure types.
    Cohrane Database of Systematic Reviews 12/2014; DOI:10.1002/14651858.CD011412.
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    Cochrane database of systematic reviews (Online) 12/2014; 12:CD010682. DOI:10.1002/14651858.CD010682.pub2 · 5.70 Impact Factor
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    ABSTRACT: Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the “classical” epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previous studies, this cohort is sufficiently large to show a significant excess of de novo mutations in epileptic encephalopathy probands compared to the general population using a likelihood analysis (p = 8.2 × 10−4), supporting a prominent role for de novo mutations in epileptic encephalopathies. We bring statistical evidence that mutations in DNM1 cause epileptic encephalopathy, find suggestive evidence for a role of three additional genes, and show that at least 12% of analyzed individuals have an identifiable causal de novo mutation. Strikingly, 75% of mutations in these probands are predicted to disrupt a protein involved in regulating synaptic transmission, and there is a significant enrichment of de novo mutations in genes in this pathway in the entire cohort as well. These findings emphasize an important role for synaptic dysregulation in epileptic encephalopathies, above and beyond that caused by ion channel dysfunction.
    The American Journal of Human Genetics 09/2014; · 11.20 Impact Factor
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    ABSTRACT: A multigenic classifier based on five single nucleotide polymorphisms (SNPs) was previously reported to predict treatment response in an Australian newly-diagnosed epilepsy cohort using a k-Nearest Neighbour (kNN) algorithm. We assessed the validity of this classifier in predicting response to initial antiepileptic drug (AED) treatment in two UK cohorts of newly-diagnosed epilepsy and investigated the utility of these five SNPs in predicting seizure control in general. The original Australian cohort constituted the training set for the classifier and was used to predict response to the first well-tolerated AED monotherapy in independently recruited UK cohorts (Glasgow, n = 281; SANAD, n = 491). A “leave-one-out” cross-validation was also employed, with training sets derived internally from the UK datasets. The multigenic classifier using the Australian cohort as the training set was unable to predict treatment response in either UK cohort. In the “leave-one-out” analysis, the five SNPs collectively predicted treatment response in both Glasgow and SANAD patients prescribed either carbamazepine or valproate (Glasgow OR = 3.1, 95% CI = 1.4-6.6, p = 0.018; SANAD OR = 2.8, 95% CI = 1.3-6.1, p = 0.048), but not those receiving lamotrigine (Glasgow OR = 1.3, 95% CI = 0.6-2.8, p = 1.0; SANAD OR = 2.2, 95% CI = 0.9-5.4, p = 0.36) or other AEDs (Glasgow OR = 0.6, 95% CI = 0.2-2.0, p = 1.0; SANAD OR = 1.9, 95% CI = 0.9-4.2, p = 0.36). The Australian-based multigenic kNN model is not predictive of initial treatment response in UK cohorts of newly-diagnosed epilepsy. However, the five SNPs identified in the original Australian study appear to collectively have a predictive influence in UK patients prescribed either carbamazepine or valproate.
    Epilepsy Research 09/2014; 108(10). DOI:10.1016/j.eplepsyres.2014.08.022 · 2.19 Impact Factor
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    ABSTRACT: To investigate the length of time taken to open UK research sites in multicentre clinical trials and to identify reasons for any delays.
    BMJ Open 09/2014; 4(9):e005874. DOI:10.1136/bmjopen-2014-005874 · 2.06 Impact Factor
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    Tom B. Mole, Richard Appleton, Anthony Marson
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    ABSTRACT: Purpose Although sodium valproate (VPA) remains the most effective antiepileptic for generalised and unclassified epilepsies, clinicians may be failing to discuss this treatment option because of guideline misinterpretation. Current guidelines recommend caution regarding teratogenic risks but do not advocate absolute avoidance. Methods We assessed VPA prescribing in young people attending a transition epilepsy clinic. We present six patients with idiopathic generalised epilepsy (IGE) in whom VPA had been initially avoided. Results Overall, the results were consistent with VPA's superior antiepileptic efficacy and ability to reduce harmful seizure-related complications. Young people denied of VPA showed prolonged periods of poor seizure control with medical, social and psychological complications. Following contraceptive counselling and VPA introduction, all six patients showed improved seizure control including seizure-freedom during follow-up of up to twenty-four months. There was also evidence of reduced seizure-related morbidity and improved educational and occupational functioning. Prior to referral, documentation revealed no discussion of VPA treatment options. Conclusion Failure to prescribe valproate for IGE, particularly when another first-line treatment has failed, may not be in a young woman's best interests particularly when they are most vulnerable to sequelae from uncontrolled seizures. Indiscriminate avoidance of valproate needs to be recognised as a misinterpretation of current epilepsy guidelines as it may harm young people. Although the use of valproate demands careful consideration, there remains a strong case to always discuss this medication because of its efficacy and potential to reduce seizure-related harm. Patients must be allowed to make their own informed decisions about effective epilepsy treatments.
    Seizure 08/2014; 24. DOI:10.1016/j.seizure.2014.08.006 · 2.06 Impact Factor
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    ABSTRACT: Background: The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods: We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p<1·66 × 10–8. Findings: We included 8696 cases and 26 157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71 × 10–10), implicating SCN1A, and at 4p15.1 (p=5·44 × 10–9), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99 × 10–9), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. Interpretation: This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these disorders, with the ultimate aim of assisting in disease classification and prognosis. The data suggest that specific loci can act pleiotropically raising risk for epilepsy broadly, or can have effects limited to a specific epilepsy subtype. Future genetic analyses might benefit from both lumping (ie, grouping of epilepsy types together) or splitting (ie, analysis of specific clinical subtypes).
    The Lancet Neurology 07/2014; · 21.82 Impact Factor
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    ABSTRACT: Epilepsy is a disease with substantial missing heritability; despite its high genetic component, genetic association studies have had limited success detecting common variants which influence susceptibility. In this paper, we reassess the role of common variants on epilepsy using extensions of heritability analysis. Our data set consists of 1258 UK patients with epilepsy, of which 958 have focal epilepsy, and 5129 population control subjects, with genotypes recorded for over 4 million common single nucleotide polymorphisms. Firstly, we show that on the liability scale, common variants collectively explain at least 26% (standard deviation 5%) of phenotypic variation for all epilepsy and 27% (standard deviation 5%) for focal epilepsy. Secondly we provide a new method for estimating the number of causal variants for complex traits; when applied to epilepsy, our most optimistic estimate suggests that at least 400 variants influence disease susceptibility, with potentially many thousands. Thirdly, we use bivariate analysis to assess how similar the genetic architecture of focal epilepsy is to that of non-focal epilepsy; we demonstrate both significant differences (P = 0.004) and significant similarities (P = 0.01) between the two subtypes, indicating that although the clinical definition of focal epilepsy does identify a genetically distinct epilepsy subtype, there is also scope to improve the classification of epilepsy by incorporating genotypic information. Lastly, we investigate the potential value in using genetic data to diagnose epilepsy following a single epileptic seizure; we find that a prediction model explaining 10% of phenotypic variation could have clinical utility for deciding which single-seizure individuals are likely to benefit from immediate anti-epileptic drug therapy.
    Brain 07/2014; 137. DOI:10.1093/brain/awu206 · 10.23 Impact Factor
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    ABSTRACT: We assessed the likelihood of 12-month seizure remission and treatment failure after failure of a first antiepileptic drug, and identified factors influencing these outcomes.METHODS: SANAD (Standard and New Antiepileptic Drug) was a randomized controlled trial comparing monotherapy with standard and new antiepileptic drugs. Patients were followed up to study completion, even if they were switched from their randomized treatment. After a first treatment failure, we assessed the probability of 12-month seizure remission and treatment failure. Prognostic modeling identified predictors of these outcomes.RESULTS: Forty-four percent of patients in the SANAD trial had a first treatment failure. Seventy-five percent of these subsequently achieved 12-month remission by 6 years of follow-up. Significant prognostic factors included sex, age at treatment failure, time on randomized treatment at treatment failure, neurologic insult, total number of tonic-clonic seizures at treatment failure, reason for treatment failure, seizure type, and CT/MRI scan result. After a first treatment failure, young patients without tonic-clonic seizures, with a normal CT/MRI scan and failing their treatment because of unacceptable adverse events, had the highest likelihood of 12-month remission. Approximately 50% of patients who failed a first treatment also failed their second. Significant prognostic factors included total number of tonic-clonic seizures at first treatment failure, reason for first treatment failure, and CT/MRI scan result. Patients with tonic-clonic seizures and failing because of inadequate seizure control had the highest risk of a second treatment failure.CONCLUSIONS: A high proportion of patients will achieve 12-month remission after a first treatment failure. Clinical factors can stratify patients according to likely outcome.
    Neurology 07/2014; DOI:10.1212/WNL.0000000000000673 · 8.30 Impact Factor
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    ABSTRACT: The study of juvenile myoclonic epilepsy is important in that: it is common and heterogeneous; the etiology is unknown; and patients report broad cognitive problems. We utilized a broad battery of neuropsychometric tests to assess the following: intellectual function, memory, language and naming, executive function, the impact of epilepsy, and antiepilepsy drug side effects. Sixty people with drug-refractory JME were interviewed, and performance was profoundly impaired across the range of tests. Impairments included the following: full-scale IQ (89, p < 0.001); processing speed (86, p < 0.001); visual memory (immediate and delayed) more affected than verbal memory; verbal fluency and inhibition (p < 0.001); and self-reported drug side effects (p < 0.001). Eighty-three percent of patients exhibited frank executive dysfunction, which was moderate to severe in 66%. Regression modeling confirmed that an early age at onset and the need for polytherapy were associated with poorer cognitive outcomes. This study confirms previous reports of executive dysfunction in a larger cohort and with greater statistical rigor. We also identified a high prevalence of neurotoxicity symptoms such as fatigue and poorer functioning across intellectual and memory tests than had previously been reported.
    Epilepsy & Behavior 07/2014; 36:124–129. DOI:10.1016/j.yebeh.2014.04.027 · 2.06 Impact Factor
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    ABSTRACT: Objective: In the United Kingdom and other European Union countries guidelines for driving following a first unprovoked seizure require the risk of another seizure in the next year to be less than 20%. Using data from one clinical trial, we previously developed a prognostic model to inform driving guidelines. The objective of this work is to externally validate our published model and demonstrate its generalisability. Methods: A cohort of 620 people with a first unprovoked seizure was used to develop the original model which included variables for aetiology, first degree relative with epilepsy, seizures only while asleep, electroencephalogram, computed tomography or magnetic resonance scan result, and treatment policy. The validation cohorts consisted of 274 (United Kingdom), 305 (Italy), and 847 (Australia) people. The model was evaluated using discrimination and calibration methods. A covariate, missing from the Italian dataset, was handled via five imputation methods. Following external validation, the model was fitted to a pooled population comprising all validation datasets and the development dataset. The model was stratified by dataset. Results: The model generalised relatively well. All methods of imputation performed fairly similarly. At six months, the risk of a seizure recurrence following a first ever seizure, based on the pooled datasets, is 15% (95% CI: (12% to 18%)) for patients who are treated immediately and 18% (95% CI: (15 to 21%)) otherwise. Individuals can be reliably stratified into risk groups according to the clinical factors included in the model. Significance: Our prognostic model, used to inform driving regulations, has been validated and consequently has been proven as a valuable tool for predicting risk of seizure recurrence following a first seizure in people with various combinations of risk factors. Additionally, there is evidence to support one worldwide overall prognostic model for risk of second seizure following a first.
    PLoS ONE 06/2014; 9(6):e99063. DOI:10.1371/journal.pone.0099063 · 3.53 Impact Factor
  • Anand Iyer, Anthony Marson
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    ABSTRACT: Introduction: Epilepsy is the most common neurological condition worldwide with significant psychosocial and physical morbidity. Its management requires expertise and good pharmacological knowledge of the available options. Areas covered: This review covers the management of focal epilepsy addressing the common questions arising through the patients' journey, including timing of starting initial treatment, monotherapy options, add-on treatment for refractory cases and withdrawal of medication during remission. Expert opinion: Initiating anti-epileptic drug (AED) treatment requires assessment of patient preferences and of evidence of benefit and harm. Evidence of benefit will come primarily from randomised controlled trials, although in epilepsy, most trials are undertaken to inform regulatory decision and have important limitations for informing clinical decisions. Evidence about harm may come not only from randomised trials but also from other sources. Most patients will start treatment following a second focal seizure. Carbamazepine and lamotrigine are good initial monotherapy options. Newer AEDs have proof of efficacy as monotherapy but evidence is insufficient to recommend them as first-line treatments. For refractory cases, there are an increasing number of AEDs available, but evidence of efficacy is primarily from placebo-controlled trials, and there is no robust evidence to inform a choice among treatments.
    Expert Opinion on Pharmacotherapy 05/2014; DOI:10.1517/14656566.2014.922544 · 2.86 Impact Factor
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    ABSTRACT: The pattern of executive dysfunction reported in juvenile myoclonic epilepsy (JME) resembles that of patients with cluster B personality disorders. This study examined whether executive dysfunction and maladaptive behavior reported in patients with JME are related. Sixty patients with drug-refractory JME were administered tests of intellect, memory, and executive dysfunction. Anxiety, depression, personality traits, impact of epilepsy, and perceived cognitive effects of antiepileptic drugs were measured. Half of the cohort exhibited moderate to severe anxiety symptoms. The patients performed most poorly on naming ability and inhibition switching. Duration of epilepsy exacerbated poor performance on inhibition switching. Females presented with pathological scores for neurotic and introvert traits and males for introvert traits. Abnormal personality traits and psychiatric disorders were associated with worse intellectual and executive functioning. People with extreme Eysenck Personality Scale - Brief Version (EPQ-BV) scores demonstrated the greatest level of executive impairment. Furthermore, the same degree of dysfunction was not seen in any individual with unremarkable EPQ-BV scores. This study indicates that specific patterns of executive dysfunction are related to maladaptive behavior in JME. Distinct behavioral patterns may be used to identify functional and anatomical differences between people with JME and for stratification to enable gene discovery.
    Epilepsy & Behavior 05/2014; 35C:72-77. DOI:10.1016/j.yebeh.2014.03.026 · 2.06 Impact Factor
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    ABSTRACT: The costs, benefits and risks associated with diagnostic imaging investigations for epilepsy surgery necessitate the identification of an optimal pathway in the pre-surgical workup. In order to assess the added value of additional investigations a full cost-effectiveness evaluation should be conducted, taking into account all of the life-time costs and benefits associated with undertaking additional investigations. This paper considers and applies the appropriate framework against which a full evaluation should be assessed. We conducted a systematic review to evaluate the progression of the literature through this framework, finding that only isolated elements of added value have been appropriately evaluated. The results from applying the full added value framework are also presented, identifying an optimal strategy for pre-surgical evaluation for temporal lobe epilepsy surgery. Our results suggest that additional FDG-PET and invasive EEG investigations after an initially discordant MRI and video-EEG appears cost-effective, and that the value of subsequent invasive-EEGs is closely linked to the maintenance of longer-term benefits after surgery. It is integral to the evaluation of imaging technologies in the work-up for epilepsy surgery that the impact of the use of these technologies on clinical decision-making, and on further treatment decisions, is considered fully when informing cost-effectiveness.
    Epilepsy research 05/2014; DOI:10.1016/j.eplepsyres.2014.02.002 · 2.48 Impact Factor
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    ABSTRACT: Previous research identifies loss as a key concept for our understanding of the impact of chronic illness. In this in-depth qualitative study, we explored the utility of the concept of loss and loss replacement as a means of gaining a fuller understanding of the implications of a diagnosis of epilepsy for overall quality of life (QOL). Potential participants were identified from the database of a large UK-based randomized controlled trial of antiepileptic drug treatment for new-onset epilepsy and selected using purposive sampling methods. In-depth interviews were conducted with 67 people; interview material was analyzed thematically. Our findings confirm ‘loss’ as a key concept in understanding epilepsy impact. Participants cited profound physical and social losses, and the links between these and psychological loss were clearly articulated. Informants described two main processes via which the linked losses they experienced occurred: personal withdrawal processes and externally enforced processes. Seizure control was integral to restoring psychological well-being and a sense of normality but was only one of a number of influences moderating the degree of loss experienced following seizure onset. Our work emphasizes that people with epilepsy (PWE) require active support for their continued engagement or reengagement in roles and activities identified as central to their psychological well-being and overall QOL. Achieving this requires a multiagency approach to drive forward key strategies for reduction of the negative impacts of epilepsy and to engender a sense of normality in the context of a condition often experienced as placing the individual outside the socially determined parameters of the ‘normal’.
    Epilepsy & Behavior 04/2014; 33:59–68. DOI:10.1016/j.yebeh.2014.02.015 · 2.06 Impact Factor
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    Jennifer Pulman, Karla Hemming, Anthony G Marson
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    ABSTRACT: Epilepsy is a common chronic neurological disease with an estimated prevalence of 1% in the UK. Approximately one third of these people continue to have seizures despite drug treatment. In order to try to improve outcomes a number of new antiepileptic drugs have been developed and pregabalin is one of these. This review is an update of a previous Cochrane review (Pulman 2008); no further studies have been added since the previous update in 2012 and only one study has been identified as an ongoing trial. To summarise evidence from randomised controlled trials regarding the efficacy and tolerability of pregabalin when used as an add-on antiepileptic treatment in drug-resistant partial epilepsy. The definitions of drug resistance used were those employed by the authors of the included trials. We searched the Cochrane Epilepsy Group Specialized Register (Jan 2014), CENTRAL (the Cochrane Central Register of Controlled Trials, The Cochrane Library 2013, Issue 12), MEDLINE (Ovid, 1946 to 09/01/2014) and contacted Pfizer Ltd. (the manufacturers of pregabalin) to identify published, unpublished and ongoing trials. We included randomised controlled trials comparing pregabalin with placebo or an alternative antiepileptic drug for people with drug-resistant partial epilepsy. Outcomes included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal for any reason, treatment withdrawal for adverse events and nature of adverse events. Two review authors (JP and AGM) independently selected and assessed suitable trials and extracted data. Primary analyses were by intention-to-treat (ITT). Results are presented as risk ratios (RR) with 95% confidence intervals (CI). Included studies were assessed for risk of bias by two authors using the Cochrane 'Risk of bias' tool. Six suitable industry-sponsored trials (2009 participants) were identified and included in the analysis. Trials tested doses of pregabalin ranging from 50 mg/day to 600 mg/day. For the primary outcome, 50% or higher seizure reduction was significantly more likely in patients randomised to pregabalin than to placebo (RR 2.61; 95% CI 1.70 to 4.01). A dose-response analysis suggested increasing effect with increasing dose. Pregabalin was significantly associated with seizure freedom (RR 2.59; 95% CI 1.05 to 6.36). Patients were significantly more likely to have withdrawn from pregabalin treatment than placebo treatment for any reason (RR 1.39; 95% CI 1.13 to 1.72) or for adverse effects (RR 2.69; 95% CI 1.88 to 3.86). Ataxia, dizziness, somnolence and weight gain were significantly associated with pregabalin. The odds of response doubled with an increase in dose from 300 mg/day to 600 mg/day (OR 2.12; 95% CI 1.76 to 2.54). Overall, the evidence was rated as low/unclear risk of bias due to the possibility of publication bias. The quality of the evidence was rated as moderate using the GRADE approach. Pregabalin, when used as an add-on drug for treatment-resistant partial epilepsy, is significantly more effective than placebo at achieving a 50% or greater seizure reduction and significantly increasing seizure freedom. Results demonstrate efficacy for doses from 150 mg/day to 600 mg/day, with increasing effectiveness at 600 mg doses. The trials included in this review were of short duration and longer-term trials are needed to inform clinical decision making better.
    Cochrane database of systematic reviews (Online) 03/2014; 3(3):CD005612. DOI:10.1002/14651858.CD005612.pub3 · 5.94 Impact Factor
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    ABSTRACT: Epilepsy is a common neurological condition characterised by recurrent seizures. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we present a summary of evidence for the use of STM as monotherapy in epilepsy. To examine the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug. We searched the Cochrane Epilepsy Group Specialised Register (24 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 9), MEDLINE Ovid (1946 to 24 October 2013), SCOPUS (1823 to 24 October 2013), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal (28 October 2013) and (28 October 2013). We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies. Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology. Two review authors independently selected trials for inclusion and extracted the relevant data.The following outcomes were assessed: (1) time to treatment failure; (2) time to 12-month remission; (3) proportion seizure free at 12 months; (4) adverse effects; and (5) quality of life scoring. Primary analyses were intention-to-treat when possible. A narrative analysis of the data was presented. Two studies representing 100 participants with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS) and one study representing 146 participants with a diagnosis of generalised tonic-clonic seizures (GTCS) were included. STM was given as monotherapy compared with placebo in the BECTS studies and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. No data were reported for outcome (1), (2), (3) or (5). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than were participants receiving phenytoin in the GTCS study (risk ratio (RR) 0.03, 95% confidence interval (CI) 0.00 to 0.58). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. Two ongoing studies comparing STM monotherapy versus placebo or levetiracetam in BECTS were identified. Small sample size, poor methodological quality and lack of data on important outcome measures prevent any meaningful conclusions regarding the efficacy and safety of sulthiame as monotherapy in epilepsy.
    Cochrane database of systematic reviews (Online) 03/2014; 3(3):CD010062. DOI:10.1002/14651858.CD010062.pub2 · 5.94 Impact Factor

Publication Stats

2k Citations
687.55 Total Impact Points


  • 2000–2015
    • University of Liverpool
      • • Department of Molecular and Clinical Pharmacology
      • • Department of Biostatistics
      • • School of Biological Sciences
      • • Department of Psychological Sciences
      Liverpool, England, United Kingdom
  • 2013
    • University College London
      Londinium, England, United Kingdom
  • 2012
    • London School of Hygiene and Tropical Medicine
      • Department of Medical Statistics
      London, ENG, United Kingdom
  • 2010–2011
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
    • Aintree University Hospital NHS Foundation Trust
      Liverpool, England, United Kingdom
  • 2008
    • The University of Warwick
      • Department of Statistics
      Warwick, ENG, United Kingdom
    • The University of Calgary
      • Department of Clinical Neurosciences
      Calgary, Alberta, Canada
  • 2006–2008
    • Imperial College London
      Londinium, England, United Kingdom
    • University of Cambridge
      • MRC Biostatistics Unit
      Cambridge, ENG, United Kingdom
  • 2007
    • The University of Hong Kong
      Hong Kong, Hong Kong
  • 2005
    • Newcastle University Medicine Malaysia
      Bharu, Johor, Malaysia
  • 1998
    • The Walton Centre NHS Foundation Trust
      Liverpool, England, United Kingdom