Abstracts

The cognitive and behavioral effects of lamotrigine (LTG) and topiramate (TPM) were compared to the self-reported drug preference of healthy adults. Drug preference is important for patient compliance and antiepileptic drug (AED) therapy. Subjective perception of cognitive and behavioral effects contribute to drug preference. Evaluating the effects of AEDs in healthy volunteers minimizes the confounding factors associated with epilepsy. A randomized, double-blind, double-dummy, two-period crossover study in healthy adults. Subjects were randomized (1:1) in the first treatment period to receive either LTG or TPM for 12 weeks (7 weeks of dose escalation followed by 4 weeks of maintenance therapy, and then a 1 week taper). Maintenance dose was 300mg/day for both AEDs. Subjects then received the alternate therapy for the next 12 weeks with the same dosing format. Evaluations were conducted at Screening, end of the First Maintenance Phase, end of the Second Maintenance Phase, and in the Post-treatment Period. Subjects were queried as to their preference for LTG vs. TPM at their last visit of the Second Maintenance Phase (subject and investigator blind). Side effects were recorded at each evaluation. Measures included mood assessment (QOLIE-89, SEALS, and POMS), and cognitive tests of attention, memory, language, and executive functioning. A total of 37 adults (mean age = 38 yrs) completed the study. Significantly more participants (26/37, 70%) preferred LTG (LTG-P). Six (16%) preferred TPM (TPM-P) and 5 (14%) had no preference (No-P). There was no difference in age or IQ between groups ([underline]p[/underline][gt].05). Overall, participants reported improved attention, memory, and language (QOLIE-89) along with less worry, tension, fatigue, and dysphoria (SEALS) on LTG regardless of drug preference. Within group differences were found. A total of 73% of subjects in the LTG-P group reported fewer side effects on LTG, while 67% of the TPM-P group had fewer problems on TPM. POMS ratings were consistent with drug preference, in which 4 of the 6 subscales favored TPM for the TPM-P group, and favored LTG for the LTG-P and No-P groups. Counter to self-report, performance on most cognitive variables declined on TPM in all 3 groups. Seventy percent of healthy volunteers preferred LTG to TPM. Congruent with their stated preference, 73% of these subjects voiced fewer drug side effects and 100% objectively performed better while on LTG. Interestingly, the 16% who preferred and reported less toxicity while on TPM all showed impairment of cognitive function objectively. Thus, factors other than cognitive performance led to preference of TPM in a subgroup of patients. (Supported by GlaxoSmithKline)