Randomized Double‐blind Parallel‐group Study Comparing Cognitive Effects of a Low‐dose Lamotrigine with Valproate and Placebo in Healthy Volunteers

Abstract

Summary:Purpose: This study aimed at investigating the cognitive and mood effects of lamotrigine (LTG) versus valproate (VPA) and placebo (PBO).Methods: By studying the effects in healthy volunteers, it is possible to separate the genuine effects of LTG from the cognitive improvements, caused by better seizure control. The study used a pretest-posttest comparison of 50 mg LTG, 900 mg VPA, or PBO in a double-blind single-dummy parallelgroup design with 30 healthy volunteers. Study duration was 12 days (with a last control on day 13). Outcome measures included cognitive tests (FePsy neuropsychological test battery), mood scales (ASL; mood-rating scale), and a scale for subjective complaints (ABNAS Neurotoxicity scale). Total sleep time was controlled with actigraphic recordings. The results were analyzed by comparing the change over time (pretest with posttest) for the three treatments with Student's t tests.Results: Cognitive tests: significant differences between the treatments were found for measurements of cognitive activation (i.e., three of the four simple reaction-time measurements showed statistically significant differences in change between PBO and LTG in favor of LTG (p ‫ס‬ 0.03; 0.03; 0.04); two of four tests showed statistically significant differences in change between LTG and VPA, both in favor of LTG (p ‫ס‬ 0.03; 0.05). Subjective complaints: the ABNAS-neurotoxicity scale reveals a significant reduction of drug-related cognitive complaints for the subjects taking LTG, relative to VPA (p ‫ס‬ 0.02). Mood rating: significant changes were found on the scale assessing "tiredness," showing increased tiredness/sedation for VPA relative to PBO (p ‫ס‬ 0.02) and on the "timid scale" for LTG reporting "being more at ease" compared with both PBO and VPA (p ‫ס‬ 0.02; 0.02). The general direction of change for the mood scales was toward "activation" for LTG (five of six scales improved), whereas for VPA, the reverse effect was found (four of six scales showed a change in the direction of "tiredness/sedation").Conclusions: Short-term treatment in normal volunteers with a low dose of LTG resulted in improved cognitive activation on simple reaction-time measurements, a more positive subjective report about the impact of drug treatment relative to VPA, and mood changes concurring with the activating effect demonstrated by the cognitive tests.

Attenuation of the Effects of Corticosteroids on Declarative Memory with Lamotrigine

“…In patients with seizures, lamotrigine appears to have a more benign effect on cognition than some other antiseizure medications (Pressler et al, 2006). In healthy controls (Aldenkamp et al, 2002) and in animal models (Shannon and Love, 2004) lamotrigine appears to be associated with no significant changes in cognitive performance. In patients with bipolar disorder, both improvement (Daban et al, 2006) and worsening of cognitive performance (Osuji et al, 2007, in press) have been reported with lamotrigine.…”

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).…”

The potential role of lamotrigine in schizophrenia

“…An open-label study in patients diagnosed with Alzheimer's disease showed some treatment improvement in depressed mood, word recognition, and naming with lamotrigine treatment (Tekin et al 1998), and lamotrigine may have a beneficial effect on cognition in patients with epilepsy (Aldenkamp and Baker 2001). Furthermore, healthy volunteers on low doses of lamotrigine showed improvement on measures of cognitive activation and alertness (Aldenkamp et al 2002).…”