Imipramine: the influence of its metabolite plasma levels on treatment response?

BackgroundIn therapeutic drug monitoring (TDM) of imipramine treatment, combined plasma levels of imipramine and its metabolite desipramine are usually assessed, often without paying attention to individual plasma levels. Imipramine and desipramine differ in their pharmacokinetic properties. Previous research suggested that high desipramine levels might negatively influence imipramine treatment efficacy in generalized anxiety disorder. We aimed to explore the relationship between separate imipramine and desipramine levels and treatment response in depressed inpatients.MethodsWe conducted a retrospective study involving inpatients with major depression disorder who underwent five-week imipramine treatment. Weekly sum levels were measured with subsequent dose adjustments until reaching adequate levels. We assessed response rates on the 17-item Hamilton Rating Scale for Depression (HDRS17) and compared imipramine and desipramine plasma levels between responders and non-responders using Mann-Whitney U tests.Results/OutcomesAfter five weeks of treatment, non-responders exhibited significantly higher desipramine levels (P = 0.015) and combined plasma levels (P = 0.020) compared to responders. Imipramine levels did not significantly differ between groups. Additionally, higher desipramine levels corresponded to smaller changes on the HDRS17, whereas higher imipramine plasma levels corresponded to greater changes. Plasma levels did not significantly differ between patients with and without concomitant CYP2D6 or CYP2C19 inhibiting medication.Conclusion/InterpretationOur findings suggest that desipramine plasma levels were higher in non-responders to imipramine treatment, implying a potential negative impact on imipramine’s therapeutic effect. In the future, it may prove important to consider metabolite plasma levels alongside combined plasma levels when performing TDM.Declaration of interest/FundingThe authors declare no conflicts of interest and received no specific funding for this research.