Abstracts

Rationale: Lamotrigine (LTG) is one of the most used antiepileptic drugs. LTG serum concentrations are useful in clinical practice. A serum concentration greater than 20 mg/L is reported to be associated with toxicity. We evaluated the pharmacological interventions that led to LTG serum concentrations of > 20 mg/L, and the clinical correlates of these concentrations.Methods: We searched our database for patients with LTG concentrations of > 20 mg/L and analyzed medication changes that preceded these serum concentrations. We also reviewed medical records for adverse experiences reported in association with these LTG concentrations.Results: 130 patients had a serum LTG concentration measurement of >20 mg/L (range 20-40.3). To evaluate the changes that led to that concentration, we identified the prior measured concentration. This was available in 121 patients and had a mean of 15.2 mg/L. The measurement of >20 mg/L represented a mean relative increase of 123%. In 80 patients, the increase in LTG concentration was not preceded by any change in dose. In four patients, the increase was related to addition of valproate, and in one it was postpartum. In the remaining 36 patients, there was a 168% mean increase in LTG concentration in response to a 36% mean change in dose. Clinical manifestations of toxicity were seen in 72 patients and included (in order of frequency) gait disturbance/disequilibrium, tremor, diminished energy, dizziness, memory loss, difficulty concentrating, sleepiness, irritable mood, insomnia, blurred/double vision, headache, depression, and nausea/vomiting. 49 patients had no reported adverse effects. The mean serum concentration was 24.6 mg/L in both groups, with and without adverse effects.Conclusions: Approximately 60% of patients with LTG serum concentration of >20 mg/L reported adverse effects. LTG may follow nonlinear kinetics at elevated concentrations in select individuals, and a large increase in concentration may be seen with a small change or even no change in dose. Close monitoring of LTG serum concentration is warranted for symptoms consistent with LTG toxicity, particularly when the baseline serum concentration has been above 15 mg/L.