CARBAMAZEPINE BUT NOT VALPROATE INDUCES BUPROPION METABOLISM

Bupropion (BUP) may be less likely than other antidepressants to cause switches into mania and rapid cycling, suggesting utility in bipolar disorder. The combination of BW with the mood-stabilizing anticonvulsa nts carbamazepine (CBZ) or valproate (VPA) is a strategy that might fu rther lessen the risk of mania. CBZ induces, and to a lesser extent WA inhibits the hepatic metabolism of various medications, but their eff ects on BUP have not been previously studied. Inpatients with mood dis orders had pharmacokinetic profiles of BUP and metabolites assessed af ter single, oral, 150-mg doses of BUP while receiving placebo (N = 17) or during chronic blind CBZ (N = 12) or VPA (N = 5) monotherapy. CBZ but not VPA therapy decreased BUP peak concentrations (C-max) by 87% ( p < 0.0001) and 24-h area under the curve (AUG) by 90% (p < 0.0001), t hreohydrobupropion C-max by 81% (p < 0.0009) and AUC by 86% (p < 0.002 ), and erythropydrobupropion C-max by 86% (p < 0.05) and AUC by 96% (p < 0.05). CBZ increased hydroxybupropion (H-BUP) C-max by 71% (p < 0.0 07) and AUC by 50% (p < 0.05). VPA increased H-BW C-max by 56% (p < 0. 09) and H-BUP AUC by 94% (p < 0.02). Thus, CBZ markedly decreased BUP and increased H-BUP concentrations, whereas VPA did not affect BUP but increased H-BUP concentrations. Further studies are required to deter mine how these differential effects of CBZ and VPA on BUP pharmacokine tics influence the tolerability and efficacy of combination therapies with these agents.