Julie Doughty

The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial

BACKGROUNDnCarbamazepine is widely accepted as a drug of first choice for patients with partial onset seizures. Several newer drugs possess efficacy against these seizure types but previous randomised controlled trials have failed to inform a choice between these drugs. We aimed to assess efficacy with regards to longer-term outcomes, quality of life, and health economic outcomes.nnnMETHODSnSANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm A recruited 1721 patients for whom carbamazepine was deemed to be standard treatment, and they were randomly assigned to receive carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate. Primary outcomes were time to treatment failure, and time to 12-months remission, and assessment was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.nnnFINDINGSnFor time to treatment failure, lamotrigine was significantly better than carbamazepine (hazard ratio [HR] 0.78 [95% CI 0.63-0.97]), gabapentin (0.65 [0.52-0.80]), and topiramate (0.64 [0.52-0.79]), and had a non-significant advantage compared with oxcarbazepine (1.15 [0.86-1.54]). For time to 12-month remission carbamazepine was significantly better than gabapentin (0.75 [0.63-0.90]), and estimates suggest a non-significant advantage for carbamazepine against lamotrigine (0.91 [0.77-1.09]), topiramate (0.86 [0.72-1.03]), and oxcarbazepine (0.92 [0.73-1.18]). In a per-protocol analysis, at 2 and 4 years the difference (95% CI) in the proportion achieving a 12-month remission (lamotrigine-carbamazepine) is 0 (-8 to 7) and 5 (-3 to 12), suggesting non-inferiority of lamotrigine compared with carbamazepine.nnnINTERPRETATIONnLamotrigine is clinically better than carbamazepine, the standard drug treatment, for time to treatment failure outcomes and is therefore a cost-effective alternative for patients diagnosed with partial onset seizures.

The SANAD study of effectiveness of valproate, lamotrigine, or topiramate for generalised and unclassifiable epilepsy: an unblinded randomised controlled trial.

BACKGROUNDnValproate is widely accepted as a drug of first choice for patients with generalised onset seizures, and its broad spectrum of efficacy means it is recommended for patients with seizures that are difficult to classify. Lamotrigine and topiramate are also thought to possess broad spectrum activity. The SANAD study aimed to compare the longer-term effects of these drugs in patients with generalised onset seizures or seizures that are difficult to classify.nnnMETHODSnSANAD was an unblinded randomised controlled trial in hospital-based outpatient clinics in the UK. Arm B of the study recruited 716 patients for whom valproate was considered to be standard treatment. Patients were randomly assigned to valproate, lamotrigine, or topiramate between Jan 12, 1999, and Aug 31, 2004, and follow-up data were obtained up to Jan 13, 2006. Primary outcomes were time to treatment failure, and time to 1-year remission, and analysis was by both intention to treat and per protocol. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN38354748.nnnFINDINGSnFor time to treatment failure, valproate was significantly better than topiramate (hazard ratio 1.57 [95% CI 1.19-2.08]), but there was no significant difference between valproate and lamotrigine (1.25 [0.94-1.68]). For patients with an idiopathic generalised epilepsy, valproate was significantly better than both lamotrigine (1.55 [1.07-2.24] and topiramate (1.89 [1.32-2.70]). For time to 12-month remission valproate was significantly better than lamotrigine overall (0.76 [0.62-0.94]), and for the subgroup with an idiopathic generalised epilepsy 0.68 (0.53-0.89). But there was no significant difference between valproate and topiramate in either the analysis overall or for the subgroup with an idiopathic generalised epilepsy.nnnINTERPRETATIONnValproate is better tolerated than topiramate and more efficacious than lamotrigine, and should remain the drug of first choice for many patients with generalised and unclassified epilepsies. However, because of known potential adverse effects of valproate during pregnancy, the benefits for seizure control in women of childbearing years should be considered.

Cross-cultural Differences in Levels of Knowledge about Epilepsy

Summary: u2002Purpose: To study how much people with epilepsy in Europe know and understand about their condition and how this might affect their lives.

Quality of Life of People with Epilepsy in Iran, the Gulf, and Near East

Summary:u2002 Purpose: To study the impact of epilepsy and its treatment on the quality of life of people living in Iran and in countries in the Gulf and Near East.

Quality of life outcomes of immediate or delayed treatment of early epilepsy and single seizures.

Objective: To compare the impact of policies of immediate vs deferred treatment in patients with few or infrequent seizures on quality of life (QoL) outcomes. Methods: We conducted a multicenter, randomized, unblinded study of immediate and deferred treatment. QoL data were collected by mail, using validated measures, for participants living in the UK and without major learning disability. Baseline questionnaires were returned by 441 adult patients; 333 returned 2-year follow-up questionnaires. This analysis is based on 331 patients (162 randomized to immediate, 169 to deferred treatment) returning both baseline and 2-year questionnaires. Results: There were no significant differences at 2 years in QoL outcomes by treatment group. Patients randomized to deferred treatment were no more likely to report impairments in general health, cognitive function, psychological well-being, or social function. The one area of functioning affected was driving, where those randomized to deferred treatment were disadvantaged. There were clear QoL impacts both of taking antiepileptic drugs and, to an even greater extent, of continuing seizures. Conclusions: In treatment uncertain patients, there is a clear trade-off between adverse effects of seizures and adverse effects of taking antiepileptic drugs, i.e., neither policy examined in our study was associated with overall quality of life gains or losses longer term.

Compliance and satisfaction with switching from an immediate-release to sustained-release formulation of valproate in people with epilepsy

OBJECTIVEnThe goal of our work was to assess compliance and patient satisfaction with switching from sodium valproate to Depakine Chrono in patients with epilepsy.nnnMETHODSnClinical, demographic, and behavioral details assessing compliance and satisfaction were collected using self-completion questionnaires at the time of inclusion in the study and 3 months after the inclusion day.nnnRESULTSnData were collected from 2031 respondents from eight European countries. There were significant differences between time 1 and time 2 of the study in seizure frequency, reported side effects, compliance, and patient satisfaction.nnnCONCLUSIONnFindings suggest that switching from sodium valproate to Depakine Chrono results in an increase in seizure-free rates, a reduction in reported side effects, an improvement in the level of compliance, and a modest improvement in patient satisfaction.

Patients' Understanding of and Adjustment to Epilepsy: Interim Findings from a European Survey

Summary: The purpose of the study was to discover how much European patients with epilepsy and their carers understand about epilepsy. This article reports the interim results for the first four European countries recruited to the study and includes data collected from 1,920 people with epilepsy and 2,136 carers. Clinical and demographic details and data on understanding of epilepsy were collected using self‐completed questionnaires mailed to members of epilepsy support groups. There were no significant differences between people with epilepsy and carers for scores on the Epilepsy Knowledge Questionnaire, although people with epilepsy were more likely to score in the higher ranges. Higher scorers on the questionnaire were more likely to be better educated, to have lower scores on the impact of epilepsy scales, to have higher scores on the adjustment to epilepsy scale, and were less likely to report feeling stigmatized. The study confirms the findings of previous studies that people with epilepsy are reasonably well informed, although some gaps in their knowledge were evident. A comparison of country differences will be made and multivariate statistical analysis will allow a better understanding of the contribution of knowledge to peoples overall adjustment to their condition.

Attitudes and practice in the provision of removable partial dentures

Objective To identify the factors shaping the pattern of removable partial denture (RPD) provision by dentists in England.Design Cross sectional survey of general dental practitioners.Methods Details of current practice and provision, influences, attitudes and demographic details were collected using a self-completion questionnaire mailed to general dental practitioners identified through the Dental Practice Board register.Results Three hundred and eighty-five questionnaires were returned by general dental practitioners from 62 health authorities throughout England. The most important factor reported as influencing both the GDPs decision to provide a partial denture and its subsequent success was patient desire to have a partial denture. Constructing the denture from cobalt chrome, advising the patient on aftercare, making time available to make minor adjustments and being responsible for design were all factors dentists associated with success of a RPD. However, for a number of dentists there was a reported divergence between knowledge and practice.Conclusion Overall it is clear that provision of partial dentures continues to be patient led. However, the decision making process is also influenced by a number of factors including time, cost and the NHS fee structure.