The longer-term cognitive effects of adjunctive antiepileptic treatment with lacosamide in comparison with lamotrigine and topiramate in a naturalistic outpatient setting

Abstract

In this retrospective controlled study, the impact of adjunctive lacosamide (LCM) on cognition in patients with epilepsy was evaluated and compared with that of topiramate (TPM) and lamotrigine (LTG) in a naturalistic outpatient setting. Cognition was investigated by means of objective assessment of executive functions (EpiTrack®) and verbal memory and by subjective ratings of self-perceived side effects (cognition, mood, and vegetative). Quality of life was assessed using the QOLIE-10 questionnaire. Patients underwent assessment at baseline and after a median follow-up interval of 32 weeks. Forty-four patients were treated with LCM, 11 with LTG, and 15 with TPM. Treatment arms differed with regard to the age at onset of epilepsy (LTG>TPM) and to seizure control from baseline to follow-up, which was best in patients whose seizures were treated with LTG (55% vs. 16% in patients whose seizures were treated with LCM and 13% in patients whose seizures were treated with TPM). Groups did not differ in the type of epilepsy, daily drug load or drug load change, nor in baseline seizure frequency. Repeated measures statistics controlling for epilepsy onset and seizure outcome showed deteriorated executive functions with TPM (F=7.5, p=0.001). On an individual level (reliable change indices), 53% of the patients whose seizures were treated with TPM showed losses in this domain (LCM 14%, LTG 27%) and none of the patients showed improvement (LCM 23%, LTG 27%; χ(2)=11.8, p=0.019). No differences in memory, quality of life, or mood were noted among patients in the three treatment arms. Subjective cognitive complaints increased in 5 of the 9 patients whose seizures were treated with TPM (LCM 1/9, LTG 0/9; χ(2)=11.9, p=0.025). The findings of this study demonstrate for the first time that the cognitive side effect profile of LCM is comparable to that of LTG and superior to that of TPM. This is indicated by both subjective and objective measures. Given the naturalistic setting and the retrospective nature of the study, a follow-up prospective, randomized trial with larger sample sizes is required to confirm these findings.