Effect of antiepileptic drug monotherapy on urinary pH in children and young adults

Objects Since alkaline urine is a risk factor for urolithiasis, the relationship between antiepileptic drugs and urinary pH was retrospectively studied in epilepsy patients treated with antiepileptic drug monotherapy for more than 1 month.Methods A total of 913 urinary samples from antiepileptic drug-treated patients were compared with 780 age-matched control samples, and with 112 samples from epilepsy patients who had not been treated with antiepileptic drugs. The antiepileptic drugs administered were carbamazepine, valproate, phenobarbital, zonisamide, sulthiame, and phenytoin.Conclusions The proportion of the acid urine in the valproate-treated patients was lower than that in controls. The proportion of the alkaline urine in the valproate-treated patients was higher than that in controls. This effect was independent of age, sex, and the serum valproate concentration. There was no significant difference in urinary pH among the epilepsy patients treated with other antiepileptic drugs, the epilepsy patients who had not been treated with antiepileptic drugs, and the controls.     

Cerebrospinal Fluid γ-Aminobutyric Acid Levels in Children with Different Types of Epilepsy: Effect of Anticonvulsant Treatment

The mean gamma-aminobutyric acid (GABA) level in lumbar CSF of 31 children with epilepsy was not significantly different from that of 41 age-matched controls. However, when the epileptic children were subdivided into untreated patients and patients treated with antiepileptic drugs, the medication-free subgroup had a significantly lower mean CSF GABA level than nonepileptic children. Patients controlled by anticonvulsant therapy had significantly higher CSF GABA levels than untreated epileptic patients. A more detailed analysis of the children taking antiepileptic medication indicated that the only drug that significantly increased GABA in CSF was valproic acid. Analysis of CSF data with respect to the seizure type of the patients showed that, compared with controls, significantly reduced average GABA levels were present in children with infantile spasms (mostly untreated) and unmedicated generalized tonic-clonic seizures, whereas treated children with generalized tonic-clonic seizures and patients with partial epilepsy (mostly treated) did not significantly differ from controls. The data provide further evidence that impairment of the central GABA system may be involved in human epilepsy.     

One-year seizure prognosis in epilepsy patients treated with antidepressants

To investigate the clinical effects of antidepressants on seizure frequency of patients with epilepsy treated with antiepileptic drugs, we retrospectively evaluated the 1-year course of seizure frequency. One hundred twenty-one patients with epilepsy treated with antidepressants and 300 patients with epilepsy not treated with antidepressants (controls) were the subjects of this study. Seizure frequency over the 1-year period of administration of antidepressants was retrospectively evaluated and compared with that for controls. In the patients with epilepsy taking antidepressants, seizure frequencies at four observation points (1, 3, 6, and 12 months after starting antidepressants) were equivalent to those of the control group. There was no significant difference in seizure frequency between first- and second-generation antidepressants. Patients with epilepsy treated with antiepileptic drugs can take antidepressants without a significant risk of exacerbation of seizures. Most antidepressants can be used for psychiatric treatment of patients with epilepsy.     

Teratogenic effects of antiepileptic drugs

Most women with active epilepsy need treatment with antiepileptic drugs during pregnancy. Antiepileptic drugs are also frequently used for other indications, such as migraine, pain syndromes, and psychiatric disorders, which are prevalent among women of childbearing age. Possible teratogenic effects of antiepileptic drugs are therefore of wide concern and the risks imposed by the drugs must be weighed against the risks associated with the disorder being treated. Adverse drug effects on the fetus can present as fetal loss, intrauterine growth retardation, congenital malformations, impaired postnatal development, and behavioural problems. For optimum use of antiepileptic drugs in women of childbearing age and rational management of epilepsy during pregnancy, a thorough understanding of the teratogenic effects of antiepileptic drugs and knowledge of the differences in risks between various treatment options are needed.     

Determining the effects of antiepileptic drugs on cognitive function in pediatric patients with epilepsy

The majority of children with epilepsy are of normal intelligence; however, a significant subset suffers from temporary or permanent cognitive impairment. Factors that affect cognitive function are myriad and include the neuropathology underlying the epilepsy, seizures, epileptiform activity, psychosocial problems, and antiepileptic drug side effects. Although cognitive impairment is often wrongly attributed to the effects of antiepileptic drugs, antiepileptic drugs do impair cognition in some children. Clinicians should be aware of the differential cognitive effects of antiepileptic drugs and should monitor cognitive function closely when adding or changing therapy. Based on published data from prospective, chronic dosing studies, phenobarbital and topiramate have the highest potential for causing cognitive dysfunction.     

Effects of antiepileptic drug therapy on heart rate variability in children with epilepsy

Impaired cardiac autonomic function may contribute to the risk of sudden unexpected death in epilepsy. Heart rate variability (HRV) is a useful tool for the detection of sympathetic-parasympathetic balance of autonomic nervous system. In the present study, epilepsy patients who had never received antiepileptic medication and those whose seizures have been successfully controlled with antiepileptic drugs were compared with each other and a control group in order to investigate the effects of epilepsy and various antiepileptic drugs on HRV. HRV were tested via 5 min ECG monitoring in 92 patients and 83 controls. Time domain parameters including SDNN, RMSSD and the frequency domain parameters including HF (reflects parasympathetic activity) and LF (reflects sympathetic activity) were assessed. In this group, 78 patients were using antiepileptic drugs including valproic acid (n=33), oxcarbazepine (n=19), phenobarbital (n=11), combined regimens (n=10) and other drugs (n=5), while 14 patients had never received antiepileptic medication. For both of the epilepsy patients groups with or without treatment, time domain parameters were found to be significantly suppressed. In addition, parasympathetic activity was found to be decreased (HF was decreased, LF/HF ratio was increased) in epilepsy patients without antiepileptic drug therapy. Our results indicate that seizure control with antiepileptic drugs may help to improve the cardiac autonomic function impairment in epilepsy patients.     

Antiepileptic drug selection in pediatric epilepsy

This review article presents information concerning treatment options for various pediatric epilepsy syndromes. The decisions made in the selection of antiepileptic drugs are deternined by a number of variables that include, but are exclusive of, risk of seizure recurrence, patient age, epilepsy syndrome, known drug reactions, and prognosis of the epilepsy syndrome. The review discusses issues pertinent to antiepileptic drug selection including simple pharmacokinetic principles, antiepileptic drug formulations, and information concerning clinical studies using some of the antiepileptic drugs. Information is provided concerning the issues of seizure recurrence. Suggested paradigms for antiepileptic drug selection for partial seizures are provided. A table of antiepileptic drug costs is provided for assistance in prescribing and advising families. Psychosocial issues pertinent to the treatment of children are discussed.     

Efficacy of levetiracetam in children with epilepsy younger than 2 years of age

Despite the high incidence of epilepsy in very young children, the availability of approved antiepileptic drugs for this population is limited. This study assessed the efficacy and tolerability of levetiracetam in children younger than 2 years of age with various types of epilepsy. A single-center, retrospective chart review of 28 patients ranging in age from 2 weeks to 22 months treated with levetiracetam over a 2.5-year period was conducted. The mean dosage of levetiracetam was 39 mg/kg per day, and the mean duration of treatment was 6.3 months. The majority of patients (54%) were also taking 1 or 2 other antiepileptic drugs. A reduction in seizure frequency was found in 54%, with 14% achieving seizure freedom. Eight patients showed no response to levetiracetam treatment. Efficacy was highest among patients with generalized epilepsy. Adverse effects occurred in 2 patients and were behavioral in nature. Levetiracetam treatment was safe and effective in this group of very young patients with various types of epilepsy.     

Discontinuation of antiepileptic drugs after pediatric epilepsy surgery

In children with medically intractable seizures, epilepsy surgery is now a widely accepted option. Successful discontinuation of antiepileptic drugs after epilepsy surgery has been reported in adults, but rarely in children. Surgical outcome and need for antiepileptic drugs after temporal and extratemporal lobe resection were retrospectively reviewed for 80 pediatric patients from the Comprehensive Epilepsy Program at the University of Alberta. For 1 year after surgery, children were maintained on at least one antiepileptic drug. Antiepileptic drug discontinuation was attempted in all patients with a nonepileptic electroencephalogram after 1 year seizure-free. Less than half of the patients (44%) eventually relapsed without antiepileptic drugs. Of the 40 patients in the temporal lobe group, 13 (32%) relapsed without antiepileptic drugs, as did 22 of the 40 extratemporal lobe resection patients (55%). Success rates for antiepileptic drug discontinuation after surgery were higher in the temporal lobe than in the extratemporal lobe group. Long-term antiepileptic drugs are not necessary in all cases, and for many children medication can be withdrawn after epilepsy surgery.     

Current evidence indicates that antiepileptic drugs are anti-ictal,not antiepileptic

Despite the large number of available drugs for epilepsy, the primary function of pharmacological therapy is the suppression of seizures, rather than the elimination of their underlying etiology, i.e. an antiepileptic effect. This paper suggests methods by which drugs could be tested for antiepileptic properties and reviews whether current antiepilectic drugs (AEDs) are antiepileptic in addition to being effective for seizure suppression.