Pharmacokinetic interaction of quetiapine and lamotrigine – victim and perpetrator?

Abstract

ABSTRACT Objective We aimed to investigate the ambiguous findings of earlier research regarding the reduction of quetiapine plasma levels when combined with lamotrigine, most likely via UDP-glucuronosyltransferase induction by lamotrigine. Methods One thousand one hundred and fifty samples, divided into four groups of patients receiving either quetiapine immediate- (IR) or extended-release (XR) without or in combination with lamotrigine were compared regarding absolute and dose-adjusted plasma concentrations. Furthermore, samples of intra-individual controls were analyzed. Results Patients receiving quetiapine IR in combination with lamotrigine showed 31% lower plasma (p = 0.002) and 23% lower dose-adjusted plasma concentrations (p = 0.004) compared to those receiving IR monotherapy. The proportion of patients with quetiapine plasma concentrations below the lower limit of the therapeutic reference range was 50% and 30% in the combination group and in patients receiving monotherapy, respectively (p = 0.03). However, no significant differences regarding plasma concentration (p = 0.13) and dose-adjusted plasma concentration (p = 0.42) were observed in patients with combination vs. monotherapy with the XR formulation of quetiapine. In the intra-individual controls, no trends could be identified, possibly due to insufficient number of samples (p > 0.05). Conclusions The combination of quetiapine IR with lamotrigine is associated with significantly lower drug concentrations of quetiapine, potentially impacting quetiapine effectiveness. For quetiapine ER, a significant interaction is less likely.