Is the salivary concentration of lamotrigine and levetiracetam associated with clinical outcome?

Abstract

Introduction: The correlation between plasma and saliva concentration of anti-seizure medication (ASM) is well established, but variability limits the acceptance of saliva-based Therapeutic Drug Monitoring (TDM). We analysed the correlation between salivary levetiracetam and lamotrigine levels, and efficacy and tolerability.

Methods: Blood and saliva samples were collected over two years. Seizure freedom was defined as three times the longest pre-treatment inter-seizure interval or at least one year seizure-free without treatment changes. Adverse effects were assessed during visits. Lamotrigine and levetiracetam saliva and plasma concentrations were compared across groups based on treatment response and adverse effects. Response and adverse events predictors were analysed using binary logistic regression.

Results: Among 296 adults with epilepsy, 84 (28 %) achieved seizure freedom. These patients were older, predominantly on monotherapy, and underwent fewer ASM trials. 27 patients (9 %) reported adverse effects and were older at epilepsy onset. Seizure-free lamotrigine users had a lower dosage (median 2 vs 3.3 mg/kg, p = 0.07), and lower plasma and salivary concentrations (median plasma 2.6 vs 3.9 mg/L, p = 0.026; median saliva 1.4 vs 2.4 mg/L, p = 0.011). No association was found between lamotrigine dosage, levels, and adverse events. Levetiracetam users reporting side effects had higher salivary concentrations (median 20 vs 14.40 mg/L, p = 0.04), while seizure-free individuals showed no difference in salivary levels, although dosages and plasma levels differed.

Conclusion: This study highlights the clinical relevance of saliva TDM, linking salivary drug levels to treatment response for lamotrigine and adverse effects for levetiracetam. Salivary ASMs levels may complement plasma TDM, enhancing individualised treatment.

Keywords: Lamotrigine; Levetiracetam; Saliva; Therapeutic drug monitoring.