ABSTRACT
Many IV antiepileptic drugs administered in emergency situations to patients with prolonged seizures have serious adverse effects. For this reason, the authors conducted a multicenter, open-label, prospective, dose-escalation study of IV valproate sodium administered to patients with epilepsy at rates of infusion of up to 6 mg/kg/minute and doses of up to 30 mg/kg. Valproate sodium had no clinically significant negative effects on blood pressure and pulse rate and caused only mild-to-moderate, reversible adverse events.
Subject(s)
Anticonvulsants/administration & dosage , Epilepsy/drug therapy , Status Epilepticus/drug therapy , Valproic Acid/administration & dosage , Acute Disease , Anticonvulsants/adverse effects , Anticonvulsants/pharmacokinetics , Blood Pressure/drug effects , Blood Pressure/physiology , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Heart Rate/drug effects , Heart Rate/physiology , Humans , Infusions, Intravenous/methods , Prospective Studies , Status Epilepticus/prevention & control , Time Factors , Treatment Outcome , Valproic Acid/adverse effects , Valproic Acid/pharmacokineticsABSTRACT
BACKGROUND: The relative cognitive and behavioral effects of lamotrigine compared with the older standard antiepileptic drugs (AED) are uncertain. OBJECTIVE: To directly compare the cognitive and behavioral effects of carbamazepine and lamotrigine. METHODS: The cognitive and behavioral effects of carbamazepine and lamotrigine were assessed in 25 healthy adults using a double-blind, randomized crossover design with two 10-week treatment periods. During each treatment condition, subjects received either lamotrigine (150 mg/day) or carbamazepine (mean 696 mg/day) adjusted to a dose to achieve midrange standard therapeutic blood levels (mean 7.6 microg/mL). Subjects were tested at the end of each AED treatment period and in three drug-free conditions (two pretreatment baselines and a final posttreatment period [1 month after last AED]). The neuropsychological test battery included 19 measures yielding 40 total variables. RESULTS: Direct comparison of the two AED revealed significantly better performance on 19 (48%) variables for lamotrigine but none for carbamazepine. Differences spanned both objective cognitive and subjective behavioral measures, including cognitive speed, memory, graphomotor coding, neurotoxic symptoms, mood factors, sedation, perception of cognitive performance, and other quality-of-life perceptions. Comparison of carbamazepine with the nondrug average revealed significantly better performance for nondrug average on 24 (62%) variables but none for carbamazepine. Comparison of lamotrigine with nondrug average revealed better performance on one (2.5%) variable for nondrug average and on one (2.5%) variable for lamotrigine. CONCLUSION: Lamotrigine produces significantly fewer untoward cognitive and behavioral effects than carbamazepine at the dosages used in this study.
