Adverse events of dual anti-seizure medication: Real-life data from a tertiary epilepsy clinic

In patients with epilepsy, adverse events (AE) of anti-seizure medication (ASM) may lead to unfavorable quality of life and non-adherence to treatment. This retrospective study aimed to identify risk factors for overall AE burden and specific AE in patients with dual ASM therapy.

All patients aged at least 18 years from a tertiary epilepsy outpatient clinic routinely complete the 19-item Liverpool Adverse Events Profile (LAEP). Demographic, epilepsy, and treatment variables were extracted from our outpatient database. Variables of clinical relevance were entered into a binary logistic regression model.

Out of 2,106 patients, dual ASM was applied to 595 patients with 98 different combinations. We focused on the five most frequent ASM combinations; levetiracetam and lamotrigine (LEV/LTG, n=108), lacosamide and levetiracetam (LCM/LEV, n=53), lamotrigine and valproic acid (LTG/VPA, n=50), levetiracetam and valproic acid (LEV/VPA, n=27), and eslicarbazepine acetate and levetiracetam (ESL/LEV, n=22). Commonly reported specific AE were sleepiness (62 %), difficulty concentrating (55 %), memory problems (53 %), tiredness (46 %), and disturbed sleep (40 %). Relevant AE burden (LAEP score ≥45) was independently associated with female sex, LEV/VPA- and LTG/VPA-dual therapy, drug resistance, as well as focal and unclassified epilepsy. Distinct AE were associated mainly with female sex (6/19 AE), focal (5/19 AE), unclassified (7/19 AE) epilepsy, and drug resistance (4/10 AE). Concerning specific AE combination, only LTG/VPA was independently associated with hair loss (OR 6.766).

After controlling for potential confounders, our study found that the two ASM combinations involving valproic acid were significantly associated with higher LAEP scores, indicating poorer tolerability. Specific adverse events, such as hair loss, were independently associated with the LTG/VPA combination. Cognitive side effects were notably prominent across all five dual ASM combinations. While dual ASM therapy is associated with an increased burden of AE, this increase appears to be moderate when therapies are individually tailored. Increased awareness and systematic screening of AE, particularly cognitive side effects, are essential to optimize treatment outcomes.