Lower sertraline plasma concentration in patients co ‐medicated with clozapine—Implications for pharmacological augmentation strategies in schizophrenia

AbstractAugmentation of antipsychotic treatment with antidepressants represents a common and beneficial treatment strategy in patients suffering from schizophrenia. Combining clozapine and the selective serotonin reuptake inhibitor (SSRI) sertraline represents a clinically important strategy in patients with therapy-resistant schizophrenia, but there is limited knowledge about mutual pharmacokinetic interactions. In the present study, we assessed the impact of clozapine on sertraline plasma concentrations. Based on a therapeutic drug monitoring (TDM) database, sertraline plasma concentrations were compared between two groups: patients receiving a combined treatment with sertraline and clozapine (N = 15) and a matched control group receiving sertraline but no clozapine (N = 17). Group differences with respect to raw and dose-adjusted concentrations were assessed using nonparametric tests. Comedication with clozapine was associated with 67% lower median sertraline plasma concentrations (16 vs. 48 ng/mL;p = .022) and 28% lower median dose-adjusted plasma concentrations (C/D; 0.21 vs. 0.29 (ng/mL)/(mg/day);p = .049) as compared to the control group. Scatter plots revealed a complex relationship between the dosage of clozapine and dose-adjusted sertraline concentrations composed of an initial decrease at clozapine doses below 300 mg, an increase between 300 and 600 mg and a final decrease at 800  mg which was best modeled by a third order polynomial term. Cotre...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research