690 research outputs found
Overtreatment in epilepsy : How it occurs and how it can be avoided
No full textIn pharmacotherapy, overtreatment may be defined as an excessive drug load (that is, excessive drug dosages or unnecessary polypharmacy) leading to a suboptimal risk-to-benefit ratio. The risk of overtreatment in the pharmacological management of epilepsy is substantial and may have serious consequences in terms of a greater incidence and severity of adverse effects. These effects can range from subtle CNS impairment to overt toxic effects, including teratogenicity. Overtreatment also causes increased treatment costs and may even lead to a paradoxical deterioration in seizure control. The prevention and correction of overtreatment requires a thorough understanding of the situations and mechanisms that lead to inappropriate prescribing of antiepileptic drugs. These include initiating treatment in conditions where it is not indicated (for example, long-term prophylaxis after head trauma or supratentorial surgery in seizure-free patients), use of excessively fast titration rates, prescription of excessively high initial target dosages, failure to consider conditions associated with reduced dosage requirements (for example, old age or comorbidities associated with impaired drug clearance), and failure to consider the dose-response characteristics of the selected drug. Many patients whose seizures do not respond to the initially prescribed medication can be optimally managed by switching to monotherapy with an alternative agent; premature use of combination therapy represents another common form of overtreatment. Overtreatment may also result from a failure to adjust the dosage to prevent or compensate for adverse pharmacokinetic or pharmacodynamic drug interactions, and from a failure to reduce drug load in patients who have not benefited from high dosages or polypharmacy. While the measurement of drug concentrations can aid in minimising adverse effects, there is also a danger of overtreatment resulting from inappropriate interpretation of drug concentration data. Continuation of drug therapy in seizure-free patients in whom the risk-benefit ratio is in favour of gradual withdrawal may also be regarded as overtreatment. Tailoring therapy to the needs of the individual patient is the key to the successful management of epilepsy. Even though the importance of complete seizure control cannot be overemphasised, no patient should be made to suffer more from the adverse effects of treatment than from the manifestations of the seizure disorder
The adverse event profile of pregabalin: A systematic review and meta-analysis of randomized controlled trials
No full textPURPOSE: Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment
emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs
display a dose-response relationship.
METHODS: We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose-response relationships of pregabalin AEs.
KEY FINDINGS: Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose-response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others. SIGNIFICANCE: Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs
performed in different condition
New and forthcoming anti-epileptic drugs.
No full textPURPOSE OF REVIEW: There is a need for newer anti-epileptic drugs (AEDs) with improved efficacy and tolerability. This article reviews AEDs introduced since 2007 and investigational compounds in clinical development.
RECENT FINDINGS: Two recently introduced AEDs, stiripentol and rufinamide, have been licensed exclusively for orphan indications, that is severe myoclonic epilepsy of infancy (stiripentol, Europe) and Lennox-Gastaut syndrome (rufinamide, Europe and the USA). This signals a welcome new trend to explore novel treatments in specific pediatric syndromes for which there are high therapeutic needs. Two additional AEDs, lacosamide and eslicarbazepine acetate, have been licensed recently for a more traditional indication, refractory partial-onset seizures. Although newly introduced agents given as adjunctive therapy have been found to be superior to placebo in reducing seizure frequency, the ultimate goal of sustained seizure freedom is rarely achieved. Therefore, the search for better agents should continue. Several investigational compounds are currently in various stages of clinical development.
SUMMARY: The recent introduction of newer AEDs has enlarged the armamentarium against epilepsy. However, newer agents had only a modest impact on the probability of achieving long-term remission. Novel strategies for the discovery and development of truly innovative AEDs are sorely needed
Withdrawing antiepileptic drugs in seizure-free patients: what are the cognitive benefits?
No full textBackground
All major antiepileptic drugs (AEDs) have cognitive side effects, but data on the extent of the problem are conflicting.
Objective
To evaluate the effect of AED withdrawal on attention, reaction time, and speed of information processing.
Design and intervention
This randomized, double-blind, placebo-controlled study, conducted in Norway, assessed 139 adult patients with epilepsy (aged 18–66 years) who had been seizure-free for at least 2 years. Exclusion criteria included juvenile myoclonic epilepsy, paroxysmal epileptiform activity on electroencephalography in patients with primary generalized epilepsy, and mental retardation. All participants were on AED monotherapy, most with carbamazepine (64%) or valproate (19%). AED treatment was discontinued over a period of 12 weeks (switch to placebo) in 64 patients, whereas AED treatment was continued in 75 patients. Neuropsychological assessments were conducted at baseline and at 7 months after the intervention (treatment discontinuation or no discontinuation) using the California Computerized Assessment Package (CalCAP®; Miller EN, Los Angeles, CA, USA). This test battery comprises four subtests of simple reaction time (RT) and six subtests that assess more-complex aspects of attention, choice RT, psychomotor speed and rapid information processing. The investigators determined the mean RTs for all subtests, as well as the total numbers of true-positive and false-positive responses for the six complex subtests (22 items tested in total). To adjust for multiple comparisons, the significance level of independent t-tests was set at P <0.01.
Outcome measures
The outcomes were the changes in CalCAP results (mean RT, true-positive responses, true-negative responses) between baseline and 7 months after the intervention.
Results
With regard to the mean RT, AED withdrawal significantly improved results on a choice RT task and on a task evaluating rapid language discrimination, compared with AED continuation (difference between baseline and 7 months: -24 ms vs 4 ms, P <0.001 for choice RT; -17 ms vs 7 ms, P = 0.003 for language discrimination). Improvements after AED withdrawal were nearly significant (P-values in the range 0.013–0.067) for three other subtests assessing complex cognitive processing and nonsignificant for all subtests evaluating simpler forms of attention and RT. With regard to true-positive responses, near-significant (P 0.05) improvements were achieved for form discrimination and language discrimination. There were no significant differences between the two groups in terms of false-positive responses. Patients receiving carbamazepine or valproate monotherapy had results that were comparable to those observed for the whole study group, but valproate withdrawal did not result in significant improvements over valproate continuation in the choice RT and language discrimination subtests.
Conclusion
Withdrawal of AED monotherapy in patients with seizure-free epilepsy can have a positive impact on the performance of tasks that require divided attention or fast information processing
Author Response: Does Screening for Adverse Effects Improve Health Outcomes in Epilepsy? A Randomized Trial
No full textSTATUS EPILEPTICUS MIGRAINOSUS: CLINICAL, ELECTROPHYSIOLOGIC, AND IMAGING CHARACTERISTICS
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Clinically important drug interactions in epilepsy: Interactions between antiepileptic drugs and other drugs.
No full textAntiepileptic drugs (AEDs) are commonly prescribed for long periods, up to a lifetime, and many patients will require treatment with other agents for the management of concomitant or intercurrent conditions. When two or more drugs are prescribed together, clinically important interactions can occur. Among old-generation AEDs, carbamazepine, phenytoin, phenobarbital, and primidone are potent inducers of hepatic enzymes, and decrease the plasma concentration of many psychotropic, immunosuppressant, antineoplastic, antimicrobial, and cardiovascular drugs, as well as oral contraceptive steroids. Most new generation AEDs do not have clinically important enzyme inducing effects. Other drugs can affect the pharmacokinetics of AEDs; examples include the stimulation of lamotrigine metabolism by oral contraceptive steroids and the inhibition of carbamazepine metabolism by certain macrolide antibiotics, antifungals, verapamil, diltiazem, and isoniazid. Careful monitoring of clinical response is recommended whenever a drug is added or removed from a patient's AED regimen
When the past challenges the present: are older antiepileptic drugs still the best choice in childhood absence epilepsy?
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