Abstracts

We previously compared the cognitive and mood effects of lamotrigine (LTG) and topiramate (TPM) in healthy volunteers. TPM decreased performance on most measures while LTG did not. This study examined the relationship of cognitive and mood measures to serum concentration of LTG and TPM in healthy volunteers. The study used a randomized, double-blind, double-dummy, two-period crossover design. 47 (mean age = 37 yrs) healthy adults completed the study. Subjects received either LTG or TPM for 12 weeks (7 wks of dose escalation, 4 wks of maintenance therapy, and 1 wk taper). Target maintenance dose was 300 mg/day for both AEDs. Subjects then received the alternate therapy with the same dosing format. Evaluations were conducted at Screening, end of the First and Second Maintenance Phases, and at Post-treatment. Measures included mood assessment (QOLIE-89, SEALS, and POMS), and cognitive tests of attention, memory, language, and executive functioning. Pearson correlations were completed between the serum concentrations at the end of LTG and TPM maintance phases and objective cognitive and subjective mood measures. Serum concentrations of LTG and TPM were obtained at the end of the maintenance dosing periods along with cognitive and mood measures. The end of maintance therapy LTG serum concentrations ranged from 1.6 - 11.6 mcg/ml (Mean = 4.80). TPM serum concentrations ranged from 2.80 - 15.80 mcg/ml (Mean = 9.40). LTG serum concentration significantly correlated with the SEALS Temper scale ([italic]r[/italic] = -.39, [italic]p[/italic] [lt] .01). TPM serum concentrations significantly correlated with Choice Reaction Time Test (CRT) - Total Time scores ([italic]r[/italic] = .31, [italic]p [/italic][lt] .05) and mood variables (i.e., AB Neurotoxicity; QOLIE Memory scale; and SEALS scales Tiredness and Worry). Each individuals performance declined on more measures during the TPM phase than during the LTG phase. LTG had little impact on objective cogntive performance. In contrast, TPM tended to decrease scores in a non-dose-dependent manner; except for the CRT - Total Time scores, which declined with higher serum concentrations. More dose-dependent effects may be observed at lower serum concentrations. Alternatively, the lack of dose dependence may be related to inter-individual variability, thus intra-individual dose-response studies may be needed. TPM and, to a lesser extent, LTG serum concentration levels had a significant assocation with subjective mood measures. (Supported by Glaxo Smith Kline.)