Carbamazepine and Lamotrigine in Healthy Volunteers: Relevance to Early Tolerance and Clinical Trial Dosage

Abstract

This study was conducted to examine the effects of acute doses of lamotrigine (LTG) and carbamazepine (CBZ) in healthy subjects and determine whether the low tendency to impairment with LTG observed in animals applied to humans. Twelve healthy men participated in a placebo-controlled, balanced, double-blind comparison of the drugs on a series of psychomotor, autonomic, sensory, and subjective variables. Variables were analyzed by analysis of variance, and p < 0.05 was considered significant. Adaptive tracking and body sway were impaired by CBZ 600 mg. CBZ 400 and 600 mg impaired smooth pursuit eye movements and also reduced mean peak saccadic velocity. No differences from placebo occurred after LTG. CBZ 600 mg increased heart rate (HR), but no drug-related changes were noted in pupil size, salivary secretion, visual near point, or subjective effects. During the controlled study, mean plasma CBZ concentrations at 2 and 6.5 h after the 600-mg dose were 5.28 and 5.36 micrograms/ml; after LTG 300 mg, they were 3.16 and 3.00 micrograms/ml. Increased CBZ saliva concentrations were significantly associated (p < 0.01) with impaired adaptive tracking, smooth and saccadic eye movements and increased HR, and plasma concentrations were associated with impaired eye movements and body sway.

Neuropsychological and Behavioral Effects of Antiepilepsy Drugs

“…The superiority of lamotrigine over older AEDs has been demonstrated in multiple healthy volunteer studies (A. P. Aldenkamp et al 2002;Cohen et al 1985;Hamilton et al 1993).…”

“…Lamotrigine is associated with fewer CNS adverse effects on measures such as eye movements and body sway than diazepam, carbamazepine, and phenytoin (Cohen et al 1985;Hamilton et al 1993), and is associated with better neuropsychological outcome compared to carbamazepine in more than half of neuropsychological measures employed (e.g., cognitive speed, memory, mood factors, sedation, perception of cognitive performance, and quality of life) in healthy volunteers . The superiority of lamotrigine over older AEDs has been demonstrated in multiple healthy volunteer studies (A. P. Aldenkamp et al 2002;Cohen et al 1985;Hamilton et al 1993).…”

Fronto-insula network activity explains emotional dysfunctions in juvenile myoclonic epilepsy: Combined evidence from pupillometry and fMRI

“…While a more recent case report suggested lamotrigine to affect eye movements in children (Das, Harris, Smyth, & Cross, 2003), an earlier study with a larger sample of healthy volunteers found no evidence for this effect (Hamilton et al, 1993) and instead related carbamazepine to alterations in smooth and saccadic eye movements. Importantly, this study found no effects on pupil dynamics and neither did another study for valproate (DeMet & Sokolski, 1999).…”

Verträglichkeit von Lamotrigin - eine Literaturübersicht

“…Einmaldosen bis 300 mg Lamotrigin hatten bei Gesunden auch in einer anderen Studie keinen Einfluss auf die Reaktionszeit [44]. 63,93], Rhabdomyolyse, Hautausschlag und Ataxie berichtet wurde [93], ferner über einen Fall mit fulminantem Leberversagen unter Lamotrigin [64].…”