[Show abstract][Hide abstract] ABSTRACT: Background and purpose Assessment of placebo and nocebo effects and evaluation of background incidence of some predefined adverse effects (AEs) of antiepileptic drugs (AEDs) in placebo-treated paediatric patients recruited in randomized controlled studies (RCTs) of refractory focal epilepsies.
We searched all add-on, double-blind, placebo-controlled trials investigating any AED in paediatric patients with focal epilepsies and extracted both for patients treated with placebo and for those treated with the active drug, number of patients, number of responders (≥50% reduction of seizure frequency) number of patients withdrawing because of AEs, number of patients with AEs, and number of patients with 11 predefined AEs. The association between placebo and active treatment AEs was also explored.
Seven RCTs were included in our study with a total of 668 children treated with the experimental drug and 634 with placebo. In placebo-treated patients, overall responder rate was 19.7% [(95% CI), (16.0, 23.4)], proportion of placebo-treated patients withdrawing because of AEs was 3.6% (2.1, 5.1%), and proportions of patients with any AE was 81.3% (68.5, 94.1%). The three most frequently reported AEs were headache (PR = 11.4%, 6.4,16.3%) somnolence (PR = 9.6%, 4.9, 14.3%), and ataxia (PR = 4.6, -1.1, 10.2). A significant correlation between placebo–treated patients and those treated with the active drug was found for the outcome measure any AE and the AEs somnolence, headache and fatigue.
Both placebo and nocebo effects assessed in this paediatric population did not differ from findings reported in adults. This is in partial contrast to what has been previously reported and with observations in other diseases. Also specific AEs, which are at least in part, caused by the background treatment, failed to show significant differences from what previously observed in adult RCTs.
Epilepsy Research 09/2014; 108(10). DOI:10.1016/j.eplepsyres.2014.09.015 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The impact of educational strategies in the management of adverse treatment effects and drug interactions in adult patients with epilepsy with comorbidities remains undetermined.
The EDU-COM study is a randomised, pragmatic trial investigating the effect of a patient-tailored educational plan in patients with epilepsy with comorbidity.
174 adult patients with epilepsy with chronic comorbidities, multiple-drug therapy and reporting at least one adverse treatment effect and/or drug interaction at study entry were randomly assigned to the educational plan or usual care. The primary endpoint was the number of patients becoming free from adverse treatment events and/or drug interactions after a 6-month follow-up. The number of adverse treatment events and drug interactions, health-related quality of life (HRQOL) summary score changes and the monetary costs of medical contacts and drugs were assessed as secondary outcomes.
The primary endpoint was met by 44.0% of patients receiving the educational plan versus 28.9% of those on usual care (p=0.0399). The control group reported a significantly higher risk not to meet successfully the primary endpoint at the end of the study: OR (95% CI) of 2.29 (1.03 to 5.09). A separate analysis on drug adverse effects and drug interactions showed that the latter were more sensitive to the effect of educational treatment. Quality of life and costs were not significantly different in the two groups.
A patient-tailored educational strategy is effective in reducing drug-related problems (particularly drug interactions) in epilepsy patients with chronic comorbidities, without adding significant monetary costs. Registered at ClinicalTrials.gov, identifier NCT01804322, (http://www.clinicaltrials.gov).
Journal of neurology, neurosurgery, and psychiatry 01/2014; 85(8). DOI:10.1136/jnnp-2013-306553 · 6.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Zonisamide is a broad spectrum antiepileptic drug with multiple mechanisms of action which has been recently approved in the US and Europe as an adjunctive therapy for refractory partial seizures in adults. AREAS COVERED: The adverse effect profile of this drug from controlled, randomized studies and open and long-term studies and case reports is described herein. EXPERT OPINION: Zonisamide has several CNS dose-dependent, metabolic and idiosyncratic adverse effects. Knowledge of these effects is essential for the prevention or minimization of several of them. For example, treatment-emergent adverse events may be prevented by slow titration; incidence of kidney stones may be reduced through an increase in fluid intake and avoidance of concomitant treatment with topiramate and/or ketogenic diet; and oligohydrosis may be prevented by hydratation and avoidance of hot temperatures. An accurate selection of patients can be useful for the prevention of some adverse effects. Psychiatric disturbances are mainly observed in predisposed subjects and patients with a previous allergic episode to sulfonamide-containing drugs are at a higher risk for developing a skin rash.
Expert Opinion on Drug Safety 07/2011; 10(4):623-31. DOI:10.1517/14740338.2011.571201 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence.
330 patients referred to an epilepsy centre who were seizure free for at least 2 years while on stable monotherapy were the study population. Discontinuation of antiepileptic drugs (AEDs) was proposed to all eligible patients or to their carers after discussion of the risks and benefits. Depending on whether they accepted or refused treatment withdrawal, the patients were stratified into two cohorts and followed up until seizure relapse or 31 March 1999, whichever came first. For each patient, records were taken of the main demographic and clinical variables.
The sample comprised 225 patients who entered the discontinuation programme and 105 who decided to continue treatment. Twenty nine patients (28%) continuing treatment had a relapse, compared with 113 (50%) of those entering the withdrawal programme. For patients continuing treatment, the probability of remission was 95% at 6 months, 91% at 12 months, 82% at 24 months, 80% at 36 months, and 68% at 60 months. The corresponding values for patients discontinuing treatment were 88%, 74%, 57%, 51%, and 48%. After adjusting for the principal prognostic factors, in patients discontinuing AEDs the risk of seizure relapse was 2.9 times that of patients continuing treatment. A relation was also found between relapse and duration of active disease, number of years of remission while on treatment, and abnormal psychiatric findings.
Seizure free referral patients on stable monotherapy who elect to withdraw drug treatment are at higher risk of seizure relapse compared with patients continuing treatment. Severity of disease and seizure free period are significant prognostic factors.