Gaebler, Arnim Johannes and Haen, Ekkehard and Ben Omar, Nagia and Endres, Katharina and Hiemke, Christoph and Schoretsanitis, Georgios and Paulzen, Michael (2023) Lower sertraline plasma concentration in patients co-medicated with clozapine-Implications for pharmacological augmentation strategies in schizophrenia. PHARMACOLOGY RESEARCH & PERSPECTIVES, 11 (2): e01065. ISSN 2052-1707,
Full text not available from this repository. (Request a copy)Abstract
Augmentation 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. Cotreatment with clozapine may lead to reduced sertraline plasma concentrations which may be explained by clozapine-induced gastrointestinal hypo-mobility already present at low doses and cytochrome P450 3A4 inducing properties at high clozapine doses. For this drug combination, clinicians should consider TDM to confirm therapeutically effective plasma concentrations of sertraline.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SEROTONIN REUPTAKE INHIBITORS; GASTROINTESTINAL HYPOMOTILITY; MAJOR METABOLITES; TREATED PATIENTS; PHARMACOKINETICS; SYMPTOMS; EFFICACY; SAFETY; PHARMACOVIGILANCE; ANTIDEPRESSANTS; clozapine; pharmacokinetics; schizophrenia; sertraline; therapeutic drug monitoring |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann, formerly Prof. Seifert) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2024 14:12 |
| Last Modified: | 16 Mar 2024 14:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60219 |
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