Carl W. Bazil

Comparison and predictors of rash associated with 15 antiepileptic drugs

Objective: To determine predictors and relative incidence of antiepileptic drug (AED)–related rash in patients taking all common AEDs. Methods: We reviewed 1,890 outpatients. Eighty-one variables were tested as potential predictors of rash. We compared the rate of rash attributed to each AED (AED rash) with the average rate of rash attributed to the other AEDs in all adults (aged ≥16 years; n = 1,649) when taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproate (VPA), or zonisamide (ZNS). We repeated this analysis for patients with and without the identified nondrug predictors of AED rash. Results: The average rate of AED rash was 2.8%. The only nondrug predictor significant in multivariate analysis was occurrence of another AED rash (odds ratio 3.1, 95% CI 1.8 to 5.1; p < 0.0001); the rate of rash in this subgroup was 8.8%, vs 1.7% in those without another AED rash. Higher AED rash rates were seen with PHT (5.9% overall, p = 0.0008; 25.0% in those with another AED rash, p = 0.001), LTG (4.8%, p = 0.00095; 14.4%, p = 0.025), and CBZ (3.7%, not significant; 16.5%, p = 0.01). Lower rates were seen with LEV (0.6% overall; p = 0.00042), GBP (0.3%, p = 0.00035), and VPA (0.7%, p = 0.01). Rash rates were also low (<1% overall) with FBM, PRM, TPM, and VGB (not significant). These AED differences remained similar in patients with and without other AED rashes. There were four cases of Stevens–Johnson syndrome involving four AEDs. Conclusions: The rate of an antiepileptic drug (AED) rash is approximately five times greater in patients with another AED rash (8.8%) vs those without (1.7%). Rash rates were highest with phenytoin, lamotrigine, and carbamazepine and low (<1%) with several AEDs.

Cross-sensitivity of skin rashes with antiepileptic drug use

Objective: To determine rates of cross-sensitivity of rash among commonly used antiepileptic drugs (AEDs) in patients with epilepsy. Methods: The incidence of AED-related rash was determined in 1875 outpatients (≥12 years), taking carbamazepine (CBZ), clobazam (CLB), felbamate (FBM), gabapentin (GBP), levetiracetam (LEV), lamotrigine (LTG), oxcarbazepine (OXC), phenobarbital (PB), phenytoin (PHT), primidone (PRM), tiagabine (TGB), topiramate (TPM), vigabatrin (VGB), valproic acid (VPA), or zonisamide (ZNS). We compared rates of rash for each AED in patients with vs those without a rash to 1) another specific AED; 2) any other AED; 3) any two other AEDs; and 4) any non-epilepsy medication. Results: A total of 14.3% (269/1,875) of patients had a rash attributed to at least one AED; 2.8% had a rash to two or more AEDs. Of patients who had a rash to CBZ and were also prescribed PHT (n = 59), 57.6% had a rash to PHT (abbreviated as CBZ → PHT: 57.6%); of patients who had a rash to PHT and were also prescribed CBZ (n = 81), rate of rash was 42% (i.e., PHT → CBZ: 42%). Other results: CBZ → LTG: 20% (n = 50); LTG → CBZ: 26.3% (n = 38); CBZ → OXC: 33% (n = 15); OXC → CBZ: 71.4% (n = 7); CBZ → PB: 26.7% (n = 30); PB → CBZ: 66.7% (n = 12); LTG → PHT: 38.9% (n = 36); PHT → LTG: 18.9% (n = 74); PB → PHT: 53.3% (n = 15); PHT → PB: 19.5% (n = 41); OXC → LTG: 37.5% (n = 8); LTG → OXC: 20% (n = 15). There was evidence of specific cross-sensitivity between CBZ and PHT, and between CBZ and PB. Conclusion: Cross-sensitivity rates between certain antiepileptic drugs (AEDs) are high, especially when involving carbamazepine and phenytoin. Specific cross-sensitivity rates provided here may be useful for AED selection and counseling in individual patients.

Recognition and Classification of Seizures in Infants

Summary: Purpose: We wished to assess the reliability of the International League Against Epilepsy (ILAE) seizure classification system applied to infantile seizures and to test a proposed new classification.

Effects of Antiepileptic Drugs on Sleep Structure Are All Drugs Equal

Good-quality sleep is an important and frequently overlooked component of general health, but it is particularly essential to patients with epilepsy. Their sleep can be affected by seizures, concurrent sleep disorders and seizure treatment. Worsening sleep can result not only in poor daytime functioning but also potentially in worsening epilepsy. The effects of antiepileptic drugs (AEDs) on sleep are of particular concern. Some agents have detrimental effects on sleep, particularly benzodiazepines and barbiturates but also phenytoin and, possibly, carbamazepine. Others, especially gabapentin, seem to actually improve sleep quality. Much research in this area is confounded by the effects of seizures and concurrent conditions on sleep, making it difficult to isolate the direct effects of AEDs on sleep. But because AEDs have independent effects on sleep quality, the choice of an appropriate agent not only determines whether seizures are completely controlled but also whether the patient performs optimally on a daily basis.

Sleep Disturbances Reported by Refractory Partial-onset Epilepsy Patients Receiving Polytherapy

Summary:u2002 Purpose: Although sleep disturbances are common in epilepsy, few studies examined the prevalence and impact of sleep disturbance in epilepsy patients. This study investigates these in a cross‐sectional survey.

Comprehensive Care of the Epilepsy Patient—Control, Comorbidity, and Cost

Summary:u2002 Traditionally, control of seizures in patients with epilepsy is viewed as the most important clinical outcome. Yet, current antiepileptic drugs (AEDs) do not always achieve this. Around 30–40% of patients remain uncontrolled despite pharmacological intervention. Poor tolerability of AEDs is a large part of the problem and contributes as much to the overall effectiveness of therapy as efficacy. Comorbid conditions are present in many patients, and appropriate management of these can further improve seizure control and quality of life. Patients with epilepsy often experience—among other disorders—neuropsychological effects, migraines, and psychological problems (especially anxiety and depression). Sleep disturbances are also common and have been shown to contribute to the intractability of seizures in some patients. Many anticonvulsant treatments have the potential to improve—or in some cases worsen—these concurrent conditions, and these properties should therefore be considered in the total care of the patient. Finally, the costs of uncontrolled epilepsy are measured not only in terms of direct healthcare‐related costs, but also in terms of lost productivity and opportunity. The indirect costs of epilepsy are substantial and account for 70–85% of total disease‐related costs. Patients with uncontrolled seizures contribute disproportionately to healthcare costs, reinforcing the need for the development of newer AEDs with improved profiles of efficacy and tolerability, but with minimal adverse effects on behavior, cognition, and sleep.

Rates and predictors of patient-reported cognitive side effects of antiepileptic drugs: An extended follow-up

PURPOSEnImpact of adverse effects of antiepileptic medications (AEDs) such as cognitive side effects (CSEs) on quality of life can be significant. Here we provide an extended follow-up to our earlier study to investigate the predictors of cognitive side effects (CSEs) and relative frequency of CSEs among all commonly used AEDs.nnnMETHODSnIn this retrospective study, medical records of 2860 adult outpatients with epilepsy seen at our center over a 12-year period who had taken one or more AEDs were examined.nnnRESULTSnOf 2860 patients, 15% had intolerable CSEs attributed to at least one AED. On multiple logistic regression analysis, independent predictors of intolerable CSEs were lack of intellectual disability and polytherapy. In polytherapy, we found that intolerable CSEs were most commonly seen with topiramate (22.8% of 281 patients), significantly more than with almost all other AEDs. This was true in monotherapy as well, with significantly more intolerable CSEs occurring with topiramate (18.5% of 54 patients) than with gabapentin, carbamazepine, lamotrigine, and levetiracetam. AEDs with consistently low rates of ICSEs included gabapentin, pregabalin, lamotrigine, levetiracetam and carbamazepine.nnnCONCLUSIONnThese data can help facilitate selection of AEDs.

Improved quality of life in patients with partial seizures after conversion to oxcarbazepine monotherapy

OBJECTIVEnQuality of life (QOL) was assessed in patients who switched to oxcarbazepine monotherapy because of the lack of efficacy or poor tolerability of their current antiepileptic drug (AED).nnnMETHODnThis open-label, single-arm study consisted of patients aged 12 >or= years with partial onset seizures. Oxcarbazepine (8-10mg/kg/day for children, 600 mg/day for adults) was titrated up over 4 weeks while the existing AED was tapered off. QOL was evaluated at baseline and end of study (Week 16) using the validated-in-epilepsy QOLIE-31 questionnaire.nnnRESULTSnFor all patients who completed the QOLIE-31 at baseline and completion, a statistically significant improvement was noted for both the composite and multi-item subscale QOL scores (P<0.05 vs baseline). Statistically significant mean percentage improvements of >or=10% from baseline (range=10.8-50.1%) were also noted. Significant improvements were seen in health-related QOL for patients who experienced seizure freedom or >or=50% reductions in seizure frequency with oxcarbazepine monotherapy.nnnCONCLUSIONSnPatients with partial seizures who switched to oxcarbazepine monotherapy showed statistically significant, clinically relevant improvements in QOL.

Do reactive post-resection "injury" spikes exist?

Summary: Purpose: New post‐resection spikes on electrocorticography (ECoG) after lesionectomy in patients with seizures may represent residual epileptogenic tissue or presumed reactive injury spikes. We investigated the existence of post‐resection injury spikes by eliminating the possibility of residual epileptogenic tissue.

Sleep structure in patients with psychogenic nonepileptic seizures.

Psychogenic nonepileptic seizures (PNES) are a significant public health problem, occurring in perhaps 25% of patients admitted to epilepsy monitoring units. Additional distinguishing characteristics for these patients would be helpful from both a clinical and a scientific standpoint. This study examines sleep structure by polysomnography in patients with PNES compared with patients with epileptic seizures (ES). ES and PNES were verified by video-EEG monitoring. All patients with PNES were evaluated by a psychiatrist. Eight female patients with PNES were compared with 10 female ES patients in the same age group. Percentage REM sleep was significantly greater for women with PNES (23+/-1%) than for those with ES (18+/-1%). There were no differences in other sleep stages, total sleep time, or sleep efficiency. REM latency was less in PNES patients although not significantly. The study suggests that patients with PNES have a sleep architecture similar to that found in major depression, known to be associated with increased REM sleep.