Ann Jacoby

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

BACKGROUND Carbamazepine 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. METHODS SANAD 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. FINDINGS For 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. INTERPRETATION Lamotrigine 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.

Quality of Life of People with Epilepsy: A European Study

Summary: Purpose: To study the impact of epilepsy and its treatment on people with epilepsy in Europe. We therefore aimed to collect data from as many countries as possible.

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

BACKGROUND Valproate 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. METHODS SANAD 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. FINDINGS For 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. INTERPRETATION Valproate 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.

The Clinical Course of Epilepsy and Its Psychosocial Correlates: Findings from a U.K. Community Study

As part of a large community‐based study, we retrospectively examined the clinical course of epilepsy in an unselected population of people who had a recent history of seizures or were receiving antiepileptic drugs (AEDs). Clinical information was collected from medical records, and information about psychosocial functioning was obtained by means of postal questionnaires sent to identified subjects. The response rate to the postal questionnaire was 71%. There were some deficiencies in the recording of clinical data, which is not unusual since data were taken from records held by primary physicians rather than from hospital clinics. Nevertheless, findings regarding the clinical course of epilepsy corresponded to those of earlier studies. Fifty‐seven percent of the sample had had at least a 2‐year seizure‐free period and 46% of subjects were currently in a remission of at least 2‐year duration. There was a clear relationship between current seizure frequency and levels of anxiety and depression, perceived impact of epilepsy, perceived stigma, and marital and employment status. The relationship of seizure frequency and other clinical variables to psychosocial function was explored by multivariate analysis techniques. The amount of variation in scores on the various measures of function accounted for by the clinical variables was small. The most important predictor was current seizure activity, which was the first variable to enter the regression analyses for six of the eight measures of psychosocial function considered. Age at epilepsy onset also emerged as a significant predictor for depression, stigma, and marital status. In individuals with epilepsy in remission, there was little evidence that psychosocial functioning was associated with length of remission, a finding which may in part reflect the nature of this study population. The results indicate that there are several more important predictors of psychopathology and social dysfunction in epilepsy and suggest several implications for treatment interventions.

Epilepsy and social identity: the stigma of a chronic neurological disorder

Epilepsy is the most common serious neurological disorder worldwide, affecting about 50 million people. In most people with epilepsy, the disorder is clinically benign. However, because of the stigma associated with having epilepsy, which is common to many cultures, there can be a negative effect on the social identity of people with the disorder, particularly for those living in resource-poor countries. In this paper, we present general theories of stigma, as well as those specific to chronic illness. We relate these theories to the stigma associated with epilepsy throughout history and across cultures. We review research on the relation between stigma and the overall quality of life of people with epilepsy. Finally, we address reduction of the stigma.

Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial

BACKGROUND The relative risks and benefits of starting or withholding antiepileptic drug treatment in patients with few or infrequent seizures are unclear. We sought to compare policies of immediate versus deferred treatment in such patients and to assess the effects of these policies on short-term recurrence and long-term outcomes. METHODS We undertook an unmasked, multicentre, randomised study of immediate and deferred antiepileptic drug treatment in 1847 patients with single seizures and early epilepsy. Outcomes comprised time to first, second, and fifth seizures; time to 2-year remission; no seizures between years 1 and 3 and between years 3 and 5 after randomisation; and quality of life. Analysis was by intention to treat. FINDINGS 404 patients invited to join the trial did not consent to randomisation; 722 were subsequently assigned immediate treatment with antiepileptic drugs and 721 were assigned deferred treatment. Immediate treatment increased time to first seizure (hazard ratio 1.4 [95% CI 1.2 to 1.7]), second seizure (1.3 [1.1 to 1.6]), and first tonic-clonic seizure (1.5 [1.2 to 1.8]). It also reduced the time to achieve 2-year remission of seizures (p=0.023). At 5-years follow-up, 76% of patients in the immediate treatment group and 77% of those in the deferred treatment group were seizure free between 3 and 5 years after randomisation (difference -0.2% [95% CI -5.8% to 5.5%]). The two policies did not differ with respect to quality of life outcomes or serious complications. INTERPRETATION Immediate antiepileptic drug treatment reduces the occurrence of seizures in the next 1-2 years, but does not affect long-term remission in individuals with single or infrequent seizures.

Epilepsy and the quality of everyday life: Findings from a study of people with well-controlled epilepsy

Epilepsy is a stigmatising disorder and available evidence suggests that its diagnosis can have important psychosocial consequences and severely reduce the quality of an individuals everyday life. A number of studies have examined the psychosocial aspects of living with epilepsy, but these have generally involved groups of patients with severe or intractable epilepsy, so that the prevalence of problems may be over-estimated. The present study examined psychosocial functioning in a group of people in whom epilepsy was well-controlled; the majority had been seizure-free for at least two years. In doing so, it drew upon a model of quality of life which incorporated physical, social and psychological domains. Among this group of people, psychosocial functioning and adjustment to epilepsy appeared high, with low reported levels of distress. This is an important finding, not least for people with epilepsy themselves.

Randomised study of antiepileptic drug withdrawal in patients in remission

A prospective multicentre randomised study of continued antiepileptic treatment vs slow withdrawal was conducted in 1013 patients who had been free of seizures for at least 2 years. Comparison of randomised and eligible, but non-randomised, patients suggests the results should be applicable to a wider patient population. By 2 years after randomisation, 78% of patients in whom treatment was continued and 59% of those in whom it was withdrawn remained seizure free, but thereafter the differences between the two groups diminished. Non-compliance with continued treatment accounted for only a small proportion of the risk to the group continuing with treatment. The most important factors determining outcome were longer seizure-free periods (reducing the risk) and more than one antiepileptic drug and a history of tonic-clonic seizures (increasing the risk). Other factors (eg, history of neonatal seizures, specific electroencephalographic features) seemed to have smaller effects, but even in such a large study the confidence intervals for these observations were wide.

The stigma of epilepsy: a European perspective.

Summary: Purpose: To study the stigma of epilepsy in a European sample.

Stigma, epilepsy, and quality of life

Despite advances in the understanding and treatment of epilepsy within the past several decades, people with this disorder continue to be stigmatized by it. Though attitudes toward people with epilepsy have improved over the years, for many people with epilepsy, stigma continues to adversely impact their psychological well-being and quality of life. The stigma of epilepsy can be linked to a number of factors, including underresourced medical services, poor seizure control, and inadequate knowledge of epilepsy. Neither informal stigma nor formal discrimination is inevitable for epilepsy patients; however, for many individuals, epilepsy remains a defining feature of their identity, and such issues are a source of considerable concern for a number of patients.