Possible drug–drug interaction between quetiapine and lamotrigine – evidence from a Swedish TDM database

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Preliminary evidence from a single study indicates that co‐medication with lamotrigine may reduce the serum concentration of quetiapine. Since both drugs are commonly used in bipolar disorder such a drug–drug interaction could be of great importance, but the findings need to be confirmed. WHAT THIS STUDY ADDS • The association between lamotrigine dosing and lowered quetiapine concentrations was confirmed in a small independent patient sample. The magnitude of the reduction (58%) indicated that the proposed drug–drug interaction may be of clinical importance. AIM The aim of the present study was to investigate a previously proposed interaction between quetiapine and lamotrigine resulting in reduced serum quetiapine concentrations. METHODS Data on 402 patients subjected to analysis of quetiapine concentration in serum were extracted from a routine therapeutic drug monitoring database. Among these patients, those concomitantly treated with lamotrigine (n= 22) were identified and matched with 22 controls receiving quetiapine while unexposed to lamotrigine. The dose‐corrected quetiapine concentrations (C : D ratios) in the two groups were compared in both paired and unpaired analyses. RESULTS Patients co‐treated with lamotrigine had a lower mean C : D ratio (0.71, 95% CI 0.46, 0.97) compared with controls (1.64, 95% CI 1.00, 2.28). Dose‐corrected quetiapine concentrations were 58% lower in patients co‐medicated with lamotrigine. CONCLUSIONS This study indicates that lamotrigine exposure is associated with substantially reduced serum concentrations of quetiapine, possibly due to induced glucuronidation. These findings need to be confirmed in experimental studies.