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Polypharmacy has recently become usual practice in the treatment of patients with mood disorders. In this article, we review the results of recent studies on metabolic drug interactions between anticonvulsants, atypical antipsychotics, and antidepressants. Important drug interactions in clinical practice may be summarized as follows. First, valproate may increase the serum level of carbamazepine and its active metabolite carbamazepine-epoxide, quetiapine, and lamotrigine. In particular, in combined regimens of lamotrigine and valproate, the dose of lamotrigine needs to be downwardly titrated, due to the potential risk of skin lesions. Second, there are numerous carbamazepine-associated interactions that need careful monitoring, because carbamazepine is a well-known inducer of CYP1A2, CYP2C9, and CYP2C19. Thus, in patients receiving carbamazepine, clinically significant decreases in serum levels may be found for drugs metabolized by these enzymes. Third, atypical antipsychotics are primarily metabolized by CYP2D6 and CYP3A4, thereby compromising the use of inhibitors of these enzymes. Fourth, most selective serotonin-reuptake inhibitors (SSRIs) are actually inhibitors of diverse enzyme systems, indicating at least potential problems with increased serum levels. While paroxetine, fluoxetine, and fluvoxamine strongly inhibit CYP enzymes, citalopram, venlafaxine, mirtazapine, and bupropion do so weakly. In conclusion, understanding drug-drug interactions is essential in planning individualized pharmacotherapy with diverse therapeutics. In treating patients with mood disorders, special concern should be paid to combination therapy using valproate, carbamazepine, and some SSRIs.
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